Idi na sadržaj

BRCA1

Ovo je bio istaknuti članak mjeseca.
S Wikipedije, slobodne enciklopedije
BRCA1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1JM7, 1JNX, 1N5O, 1OQA, 1T15, 1T29, 1T2U, 1T2V, 1Y98, 2ING, 3COJ, 3K0H, 3K0K, 3K15, 3PXA, 3PXB, 3PXC, 3PXD, 3PXE, 4IFI, 4IGK, 4JLU, 4OFB, 4U4A, 4Y18, 4Y2G

Identifikatori
AliasiBRCA1
Vanjski ID-jeviOMIM: 113705 MGI: 104537 HomoloGene: 5276 GeneCards: BRCA1
Lokacija gena (čovjek)
Hromosom 17 (čovjek)
Hrom.Hromosom 17 (čovjek)[1]
Hromosom 17 (čovjek)
Genomska lokacija za BRCA1
Genomska lokacija za BRCA1
Bend17q21.31Početak43,044,295 bp[1]
Kraj43,170,245 bp[1]
Lokacija gena (miš)
Hromosom 11 (miš)
Hrom.Hromosom 11 (miš)[2]
Hromosom 11 (miš)
Genomska lokacija za BRCA1
Genomska lokacija za BRCA1
Bend11 65.18 cM|11 DPočetak101,379,590 bp[2]
Kraj101,442,781 bp[2]
Obrazac RNK ekspresije


Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• vezivanje tubulina
• vezivanje iona metala
• vezivanje enzima
• vezivanje iona cinka
• oštećeno vezivanje sa DNK
• GO:0001948, GO:0016582 vezivanje za proteine
• GO:0001105 transcription coactivator activity
• androgen receptor binding
• vezivanje sa RNK
• ubiquitin protein ligase binding
• GO:0050372 aktivnost sa transferazom ubikvitina
• vezivanje sa DNK
• aktivnost sa transferazom
• RNA polymerase binding
• vezivanje identičnih proteina
Ćelijska komponenta• kompleks BRCA1-BARD1
• kondenzovani nuklearni hromosom
• kompleks BRCA1-A
• kompleks ubikvitin-ligaze
• ćelijska membrana
• nukleoplazma
• kondenzovani hromosom
• citoplazma
• hromosom
• jedro
• lateralni element
• GO:0009327 makromolekulani kompleks
• ribonukleoprotein
Biološki proces• response to ionizing radiation
• centrosome cycle
• hromosomska segregacija
• protein K6-linked ubiquitination
• intrinsic apoptotic signaling pathway in response to DNA damage
• ćelijski ciklus
• double-strand break repair via nonhomologous end joining
• GO:0097285 apoptoza
• regulation of apoptotic process
• regulation of gene expression by genetic imprinting
• GO:0009373 regulation of transcription, DNA-templated
• negative regulation of fatty acid biosynthetic process
• transcription, DNA-templated
• regulation of transcription by RNA polymerase III
• fatty acid biosynthetic process
• regulation of DNA methylation
• negative regulation of intracellular estrogen receptor signaling pathway
• protein autoubiquitination
• positive regulation of histone H3-K9 methylation
• DNA recombination
• positive regulation of angiogenesis
• response to estrogen
• cellular response to indole-3-methanol
• negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
• GO:0045996 negative regulation of transcription, DNA-templated
• positive regulation of protein ubiquitination
• androgen receptor signaling pathway
• negative regulation of centriole replication
• Postreplikacijska reparacija
• lipid metabolism
• cellular response to tumor necrosis factor
• GO:1900404 positive regulation of DNA repair
• fatty acid metabolic process
• GO:1901313 positive regulation of gene expression
• negative regulation of histone H3-K4 methylation
• regulation of cell population proliferation
• negative regulation of reactive oxygen species metabolic process
• positive regulation of vascular endothelial growth factor production
• DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator
• GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
• positive regulation of histone H4-K20 methylation
• DNA double-strand break processing
• double-strand break repair via homologous recombination
• negative regulation of histone acetylation
• protein ubiquitination
• positive regulation of histone H3-K4 methylation
• GO:0100026 Popravka DNK
• double-strand break repair
• positive regulation of histone acetylation
• dosage compensation by inactivation of X chromosome
• negative regulation of histone H3-K9 methylation
• positive regulation of histone H3-K9 acetylation
• GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
• chordate embryonic development
• positive regulation of histone H4-K16 acetylation
• cellular response to DNA damage stimulus
• protein deubiquitination
• Replikacija DNK
• mitotic G2/M transition checkpoint
• GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1950094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II
• negative regulation of G0 to G1 transition
• transcription by RNA polymerase II
• mitotic G2 DNA damage checkpoint signaling
• regulation of signal transduction by p53 class mediator
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

672

12189

Ensembl

ENSG00000012048

ENSMUSG00000017146

UniProt

P38398

P48754

RefSeq (mRNK)
NM_007294
NM_007295
NM_007296
NM_007297
NM_007298

NM_007299
NM_007300
NM_007301
NM_007302
NM_007303
NM_007305
NM_007306

NM_009764

RefSeq (bjelančevina)

NP_009225
NP_009228
NP_009229
NP_009230
NP_009231

NP_033894

Lokacija (UCSC)Chr 17: 43.04 – 43.17 MbChr 11: 101.38 – 101.44 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Protein osjetljivosti na rak dojke tip 1 je protein koji je kod ljudi kodiran genom BRCA1.[5] Ortolozi su česti kod drugih kičmenjačkih vrsta, dok genomi beskičmenjaka mogu imati srodni gen.[6] BRCA1 je ljudski gen supresije tumora [7][8] (poznat i kao domarski gen) i odgovoran je za popravak DNK.[9]

BRCA1 i BRCA2 su nepovezani proteini,[10] ali oba se normalno eksprimiraju u ćelijama dojke i drugom tkivu, gdje pomažu u popravljanju oštećene DNK ili uništavanju ćelija, ako DNK nije moguće popraviti. Oni su uključeni u popravak hromosomskog oštećenja s važnom ulogom u nepogrešivim popravcima prekida dvolančana DNK.[11][12] Ako su BRCA1 ili BRCA2 sami oštećeni BRCA mutacijom, oštećena DNK se ne popravlja pravilno, a to povećava rizik za rak dojke.[13][14] BRCA1 i BRCA2 opisani su kao "geni osjetljivosti na rak dojke" i "proteini osjetljivosti na rak dojke". Prevladavajući alel ima normalnu funkciju supresije tumora, dok mutacije s visokom penetrabilnošću u ovim genima uzrokuju gubitak funkcije supresije tumora, što korelira s povećanim rizikom od raka dojke.[15]

BRCA1 se kombinira s drugim supresorima tumora, senzorima oštećenja DNK i pretvaračima signala da bi stvorio veliki kompleks multijedinica proteina poznat kao BRCA1-asocirani kompleks za nadzor genoma (BASC).[16] Protein BRCA1 povezuje se s RNK-polimerazom II, te putem C-terminalnog domena takođe komunicira sa kompleksima histon-deacetilaza. Dakle, ovaj protein ima ulogu u transkripciji i popravljanju prekida dvolančane DNK[14] ubikvitinaciji, transkripcijskoj regulaciji, kao i drugim funkcijamaa.[17]

Metodi za ispitivanje vjerovatnoće pacijenta sa mutacijama u BRCA1 i BRCA2 koje uzrokuju rak obuhvaćene su patentima u vlasništvu ili pod kontrolom Myriad Genetics. Myriadov poslovni model nuđenja dijagnostičkog testa vodio je isključivo od toga da je 1994. bio startup kompanija, koja je bila javna kompanija sa 1.200 zaposlenih i oko 500 miliona dolara godišnjeg prihoda u 2012.;[18][19] to je također dovelo do kontroverze oko visokih cijena i nemogućnosti dobivanja drugih mišljenja od drugih dijagnostičkih laboratorija, što je zauzvrat dovelo do značajne tužbe Udruženja za molekulsku patologiju protiv Association for Molecular Pathology v. Myriad Genetics.[20]

Otkriće

[uredi | uredi izvor]

Prve dokaze o postojanju gena koji kodira enzim za obnavljanje DNK, uključenog u osjetljivost na rak dojke pružio je laboratorij Mary-Claire King na University of California, Berkeley, 1990.[21] Četiri godine kasnije, nakon međunarodne utrke za pronalaženje ,[22] gen su 1994. godine klonirali naučnici sa Univerziteta u Utahu, Nacionalnog instituta za nauke o zdravlju i životnoj sredini (NIEHS) i Myriad Genetics.[23]

Lokacija gena

[uredi | uredi izvor]

Ljudski gen BRCA1 nalazi se na dugom (q) kraku hromosoma 17 u području 2, opseg 1, između baznih parova 41,196.312 i 41,277.500 (Build GRCh37/hg19)[24]Nacionalni centar za biotehnološke informacije, SAD, Nacionalna biblioteka za medicinu i [25] EntrezGene imaju referentne informacije za BRCA1 raka dojke 1, rani početak (Homo sapiens). Ortolozi BRCA1 identificirani su u većini kičmenjaka za koje su dostupni kompletni podaci o genomu.[6]

Struktura proteina

[uredi | uredi izvor]

Protein BRCA1 sadrži sljedeće domene:[26]

Ovaj protein takođe sadrži motive signala jedarne lokalizacije i signala jedarnog eksporta.[27]

Ljudski BRCA1 protein sastoji se od četiri glavna proteinska domena; Znf C3HC4- RING domen, domen BRCA1 i dva BRCT domena. Ovi domeni kodiraju približno 27% BRCA1 proteina. Poznato je šest izoformi BRCA1,[28] sa izoformama 1 i 2 koje sadrže po 1.863 aminokiseline.

BRCA1 nije povezan sa BRCA2, tj. oni nisu homolozi ili paralozi.[10]

text
Mapa domena BRCA1; označeni su RING-domeni koji sadrže serin (SCD) i BRCT. Horizontalne crne linije označavaju domene koji vežu proteine za navedene partnere. Crveni krugovi označavaju mjesta fosforilacije.[29]

Funkcija i mehanizam

[uredi | uredi izvor]

BRCA1 je dio kompleksa koji popravlja dvostruke niti u DNK. Lanci dvostruke zavojnice DNK neprekidno se lome jer se oštećuju. Ponekad je oštećen samo jedan polulanac, ponekad se oba prekidaju istovremeno. Sredstva za umrežavanje DNK važan su izvor oštećenja hromosoma/DNK. Dvolančane pukotine nastaju kao međuprodukti nakon uklanjanja umrežavanja i zaista su identificirane bialelne mutacije u BRCA1, odgovorne za Fanconijevu anemiju, komplementacijsku skupinu S,[30] genetiku bolest povezanu sa preosjetljivošću na agense za umrežavanje DNK. BRCA1 je dio proteinskog kompleksa koji popravlja DNK kad su oštećene obje niti. Kada se to dogodi, mehanizam za popravak teško može "znati" kako zamijeniti ispravnom sekvencom DNK, a postoji više načina za pokušaj popravka. Dvolančani mehanizam za popravak u kojem sudjeluje BRCA1 je homologmo usmjereni popravak, gdje popravni proteini kopiraju identičnu sekvencu iz netaknute sestrinske hromatide.[31]

U jedru mnogih tipova normalnih ćelija, protein BRCA1 tokom popravljanja dvonitnih preloma DNK komunicira sa RAD51.[32] Ti prekidi mogu biti uzrokovani prirodnim zračenjem ili drugim izlaganjem, ali se mogu dogoditi i kada hromosom razmijeni genetički materijal (homologna rekombinacija, npr."krosingover" tokom mejoze). Protein BRCA2, koji ima funkciju sličnu funkciji BRCA1, također djeluje s proteinom RAD51. Utičući na sanaciju oštećenja DNK, ova tri proteina imaju ulogu u održavanju stabilnosti ljudskog genoma.

BRCA1 je također uključen u drugi tip popravke DNK, zvani popravak neusklađenosti. BRCA1 stupa u interakciju s proteinom za popravak neusklađenosti DNK MSH2.[33] Objavljeno je da su MSH2, MSH6, PARP i neki drugi proteini koji su uključeni u popravak jednog lanca povišeni u tumorima dojke s nedostatkom BRCA1.[34]

Protein zvani valozin-sadržavajući protein (VCP, poznat i kao p97) ima ulogu u regrutaciji BRCA1 na oštećena mjesta DNK. Nakon ionizujućeg zračenja, VCP se regrutuje u lezije DNK i sudjeluje sa ubikvitin-ligazom RNF8, kako bi se orkestrirao sklop signalnih kompleksa za efikasnu popravku DSB.[35] BRCA1 komunicira sa VCP.[36] BRCA1 također komunicira i s c-Myc i drugim proteinima koji su presudni za održavanje stabilnosti genoma.[37]

BRCA1 se izravno veže za DNK, sa većim afinitetom za razgranate DNA strukture. Ova sposobnost vezanja za DNK doprinosi njenoj sposobnosti da inhibira aktivnost kompleksa nukleaza MRN, kao i aktivnost same nukleaze Mre11.[38] Ovo može objasniti ulogu BRCA1 u podsticanju popravka DNK manje vjernosti pomoću nehomolognog spajanja krajeva (NHEJ).[39] BRCA1 se također kolokalizira sa γ-H2AX (histon H2AX fosforiliran na serinu-139) u žarištima popravljanja dvostrukih lanaca DNK, što ukazuje da može imati ulogu u regrutovanju faktora popravka.[17][40]

Formaldehid i acetaldehid uobičajeni su izvori poprečnih prekida DNK, često zahtijevajući popravke posredovane putem BRCA1, koji sadrži puteve.[41]

Ova funkcija popravljanja DNK je ključna; miševi sa mutacijama gubitka funkcije u oba BRCA1 alela nisu održivi, a od 2015. godine poznato je da samo dvije odrasle osobe imaju takve mutacije; obje su imale urođene ili razvojne probleme, kao i kancer. Pretpostavljalo se da je jedna preživjela u odrasloj dobi, jer je jedna od mutacija BRCA1 bila hipomorfna.[42]

Transkripcija

[uredi | uredi izvor]

Pokazano je da BRCA1 ko-pročišćava s ljudskom RNK-polimerazom II, holoenzimom u ekstraktima HeLa, implicirajući da je komponenta holoenzima.[43] Kasnija istraživanja, međutim, proturječila su ovoj pretpostavci, umjesto da su pokazala da je dominantni kompleks koji uključuje BRCA1 u HeLa ćelijama kompleks od dva megadaltona koji sadrži SWI/SNF.[44] SWI / SNF je kompleks za remodeliranje hromatina. Pokazalo se da vještačko vezivanje BRCA1 za hromatin ne kondenzira heterokromatin, iako domen interakcije SWI / SNF nije bilo potreban za ovu ulogu.[40] BRCA1 stupa u interakciju s NELF-B (COBRA1 ) podjedinica kompleksa NELF.[40] BRCA1 je u interakciji sa NELF-B (COBRA1) podjedinicom NELF kompleksa.[40]

Mutacije i rizik od raka

[uredi | uredi izvor]

Određene varijacije gena BRCA1 dovode do povećanog rizika za raka dojke, kao dio nasljednog sindroma raka dojke-jajnika. Istraživači su identificirali stotine mutacija u genu BRCA1 , od kojih su mnoge povezane s povećanim rizikom od raka. Žene s abnormalnim genom BRCA1 ili BRCA2 imaju do 80% rizika od razvoja raka dojke do 90. godine; povećani rizik od razvoja raka jajnika je oko 55% za žene s BRCA1 mutacijama i oko 25% za žene s mutacijama BRCA2.[45]

Ove mutacije mogu biti promjene na jednom ili malom broju baznih parova DNK (građevni blokovi DNK) i mogu se identificirati pomoću PCR-a i sekvenciranja DNK.

U nekim slučajevima se preuređuju veliki segmenti DNK. Ti veliki segmenti, koji se nazivaju i velikim rearanžmanima, mogu biti delecija ili duplikacija jednog ili nekoliko egzona u genu. Klasični metodi za otkrivanje mutacija (sekvenciranje) nisu u stanju da otkriju ove tipove mutacija.[46] Predloženi su i drugi metodi: standardna kvantitativna PCR-analiza,[47] multipleks ligacijski-ovisne sonde (MLPA),[48] i kvantitativni multipleksni PCR kratkih fluorescentnih fragmenata (QMPSF).[49] Nedavno su predložene i novije metode: heterodupleksna analiza (HDA) multikapilarnom elektroforezom ili također namjenskim sekvenciranjem oligonukleotida, zasnovanom na upordnoj hibridizaciji genoma (mreža-CGH).[50]

Neki rezultati sugeriraju da bi se hipermetilacija promotora BRCA1, koji je prijavljen kod nekih karcinoma, mogao smatrati mehanizmom za inaktivaciju ekspresije BRCA1.[51]

Mutirani gen BRCA1 obično stvara protein koji ne funkcionira pravilno. Vjeruje se da neispravni protein BRCA1 nije u stanju pomoći u popravljanju oštećenja DNK, što dovodi do mutacija drugih gena. Ove mutacije mogu se akumulirati i omogućiti ćelijama nekontrolirani rast i dijeljenje, kako bi stvorile tumor. Dakle, inaktivacijske mutacije BRCA1 dovode do predispozicije za rak.

BRCA1 iRNK 3'UTR može biti vezana za miRNK, Mir-17 mikroRNK. Sugerira se da bi varijacije ove miRNA zajedno sa Mir-30 mikroRNK mogle izazvati osjetljivost na rak dojke.[52]

Pored karcinoma dojke, mutacije gena BRCA1 takođe povećavaju rizik od karcinoma jajnika i prostate. Šta više, prekancerozne lezije (displazija) unutar jajovoda povezane su s mutacijama gena BRCA1. Patogene mutacije bilo gdje u putevima modela koji sadrže BRCA1 i BRCA2 uveliko povećavaju rizike za podskupinu leukemija i limfoma.

Žene koje su naslijedile neispravan gen BRCA1 ili BRCA2 uveliko imaju povećan rizik od razvoja karcinoma dojke i jajnika. Njihov rizik od razvoja karcinoma dojke i/ili jajnika toliko je visok i toliko je specifičan za te karcinome da se mnogi nositelji mutacija odluče na profilaksnu operaciju. Bilo je mnogo nagađanja koja objašnjavaju tako očigledno zapanjujuću specifičnost tkiva. Glavne odrednice gdje se javljaju nasljedni karcinomi BRCA1/2 povezane su sa tkivnom specifičnošću patogena raka, agensa koji uzrokuje hroničnu upalu ili karcinogenezu. Ciljno tkivo može imati receptore za patogen, može biti selektivno izloženo upalnom procesu ili karcinogenu. Urođeni genomski u nedostatak gena za supresiju tumora narušava normalne reakcije i pogoršava osjetljivost na bolesti u organima- metama. Ova teorija također uklapa podatke za nekoliko tumorskih supresora izvan BRCA1 ili BRCA2. Glavna prednost ovog modela je u tome što sugerira da se uz profilaksnu operaciju mogu obaviti i neke druge opcije.[53]

Mutacija BRCA1 u raku dojke i jajnika

[uredi | uredi izvor]

Samo oko 3% –8% svih žena s rakom dojke ima mutaciju u BRCA1 ili BRCA2.[54] Slično tome, mutacije BRCA1 nađene su samo kod oko 18% karcinoma jajnika (13% mutacija zametnih linija i 5% somatskih mutacija).[55]

Prema tome, dok je ekspresija BRCA1 kod većine ovih karcinoma niska, mutacija BRCA1 nije glavni uzrok smanjene ekspresije. Određeni latentni virusi, koji se često otkrivaju u tumorima raka dojke, mogu smanjiti ekspresiju gena BRCA1 i izazvati razvoj tumora dojke.[56]

Karcinom dojke (uključujući i muški): Međuodnosi fenotip – genotip[57][58][59]

Lokacija Fenotip Fenotipski MIM broj Nasljeđivanje

oznaka mutacije

Ključ fenotipskog mapiranja Oznaka lokusa Genski/lokusni MIM broj
1p34.1 Invazivni duktusni 114480 AD*, SMu 3 RAD54L 603615
2q33.1 Zaštitni 114480 AD, SMu 3 CASP8 601763
2q35 Podložnost 114480 AD, SMu 3 BARD1 601593
3q26.32 Somatski 114480 3 PIK3CA 171834
5q34 Podložnost 114480 AD, SMu 3 HMMR 600936
6p25.2 Podložnost (?) 114480 AD, SMu 1 NQO2 160998
6q25 1-q25.2 Somatski 114480 3 ESR1 133430
8q11.23 Somatski 114480 3 RB1CC1 606837
11p15.4 Somatski 114480 3 SLC22A1L 602631
11q22.3 Podložnost 114480 AD, SMu 3 ATM 607585
12p12.1 Somatski 114480 3 KRAS 190070
13q13.1 Podložnost, muški 114480 AD, SMu 3 BRCA2 600185
14q32.33 Podložnost 114480 AD, SMu 3 XRCC3 600675
14q32.33 Somatski 114480 3 AKT1 164730
15q15.1 Podložnost 114480 AD, SMu 3 RAD51 179617
16p12.2 Podložnost 114480 AD, SMu 3 PALB2 610355
16q22.1 Režanjski 114480 AD, SMu 3 CDH1 192090
17q21.33 Podložnost 114480 AD, SMu 3 PHB 176705
17p13.1 Somatski 114480 3 TP53 191170
17q23.2 Somatski 114480 3 PPM1D 605100
17q23.2 Ranopojavna podložnost 114480 AD, SMu 3 BRIP1 605882
22q12.1 Podložnost 114480 AD, SMu 3 CHEK2 604373

Promotorska hipermetilacija BRCA1 u raku dojke i jajnika

[uredi | uredi izvor]

Promotorska hipermetilacija BRCA1 bila je prisutan u samo 13% neizabranih primarnih karcinoma dojke.[60] Slično tome, hipermetilacija promotora BRCA1 bila je prisutna u samo 5% do 15% slučajeva EOC-a.

Dakle, dok je ekspresija BRCA1 kod ovih karcinoma niska, metilacija promotora BRCA1 samo je manji uzrok smanjene ekspresije.

MikroRNK represija BRCA1 kod karcinoma dojke

[uredi | uredi izvor]

Postoji niz specifičnih mikroRNK, , koje, kada su prekomerno eksprimirane, direktno smanjuju ekspresiju specifičnih proteina koji popravljaju DNK (vidi mikroRNK, odjeljak: popravak DNK i rak). U slučaju raka dojke, mikroRNK-182 (miR-182) specifično cilja BRCA1.[61] Rak dojke može se klasificirati na osnovu statusa receptora ili histoloških obilježja, u trostruko negativni rak dojke (15% –25% karcinoma dojke), HER2 (15% –30% karcinoma dojke), ER / PR (oko 70% karcinoma dojke) i Invazivni režanjski karcinom (oko 5% –10% invazivnog karcinoma dojke). Utvrđeno je da sva četiri tipa karcinoma dojke u prosjeku imaju oko 100 puta veći porast miR-182 u odnosu na normalno tkivo dojke.[62] U ćelijskim linijama karcinoma dojke postoji inverzna korelacija nivoa proteina BRCA1 sa ekspresijom miR-182. Stoga se čini da je velik dio smanjenja ili odsustva BRCA1 kod duktusnih karcinoma dojke visokog stepena prekomjerno eksprimirani miR-182.

Pored miR-182, par gotovo identičnih mikroRNK, miR-146a i miR-146b-5p, također potiskuju ekspresiju BRCA1. Ove dvije mikroRNK su prekomjerno eksprimirane u trostruko negativnim tumorima i njihova prekomjerna ekspresija rezultira inaktivacijom BRCA1. Dakle, miR-146a i / ili miR-146b-5p mogu također doprinijeti smanjenoj ekspresiji BRCA1 kod ovih trostruko negativnih karcinoma dojke.

MikroRNK represija BRCA1 kod karcinoma jajnika

[uredi | uredi izvor]

I u seroznim tubulskim intraepitelnim karcinomima (prethodnica lezije visokoeksprimiranog seroznog karcinoma jajnika (HG-SOC)), i u samom HG-SOC, miR- 182 je prekomjerno eksprimiran u oko 70% slučajeva.[63] Dakle, miR-146a i / ili miR-146b-5p mogu takođe doprinijeti smanjenoj ekspresiji BRCA1 kod ovih trostruko negativnih karcinoma dojke.

Još jedna mikroRNK za koju je poznato da smanjuje ekspresiju BRCA1 u ćelijamama raka jajnika je miR-9. Među 58 tumora pacijenata sa stadijem IIIC ili stadijem IV seroznog karcinoma jajnika (HG-SOG), pronađena je inverzna korelacija između ekspresija miR-9 i BRCA1, tako da povećani miR-9 kod ovih karcinoma jajnika također može doprinijeti smanjenoj ekspresiji BRCA1.

Nedostatak ekspresije BRCA1 – vjerovatno tumorogen

[uredi | uredi izvor]

Oštećenje DNK je primarni uzrok raka,[64] a izgleda da su nedostaci u popravljanju DNK u osnovi mnogih oblika raka.[65] Ako je popravak DNK nedostatan, oštećenje DNK se akumulira. Takav višak oštećenja DNK može povećati mutacijske greške tokom replikacije zbog sklonosti greškama sintezi translezije. Prekomjerna oštećenja DNK mogu također povećati epigenetičke promjene, zbog grešaka tokom popravka DNK.[66][67] Takve mutacije i epigenetičke promjene mogu dovesti do karcinoma. Česti nedostatak BRCA1 izazvan mikroRNK kod karcinoma dojke i jajnika vjerovatno pridonosi njihovom napredovanju.

Populacija ili podrrupa Mutacija BRCA1[68] Reference
Afroamerikanci 943ins10, M1775R [69]
Afrikanci E881X, 1374delC [70][71]
Aškenazi Jevreji 185delAG, 188del11, 5382insC [72][73]
Austrijanci 2795delA, C61G, 5382insC, Q1806stop [74]
Belgijanci 2804delAA, IVS5 3A>G [75][76]
Nizozemci Delecija egzona 2, delecija egzona 3, 2804delAA [75][77][78]
Finci 3745delT, IVS11-2A>G [79][80]
Francuzi 3600del11, G1710X [81]
Francuski Kanađani C4446T [82]
Nijemci 5382insC, 4184del4 [83][84]
Grci 5382insC [85]
Mađari 300T>G, 5382insC, 185delAG [86]
Italijani 5083del19 [87]
Japanci L63X, Q934X [88]
Autohtoni Amerikanci 1510insG, 1506A>G [89]
Sjeverni Irci 2800delAA [90]
Norvežani 816delGT, 1135insA, 1675delA, 3347delAG [91][92]
Pakistanci 2080insA, 3889delAG, 4184del4, 4284delAG, IVS14-1A>G [93]
Poljaci 300T>G, 5382insC, C61G, 4153delA [94][95]
Rusi 5382insC, 4153delA [96]
Škoti 2800delAA [90][97]
Španci R71G [98][99]
Šveđani Q563X, 3171ins5, 1201del11, 2863delC [69][100]

Hemoterapija kancera

[uredi | uredi izvor]

Nemaloćelijski rak pluća (NSCLC) vodeći je uzrok smrti od raka u svijetu. Pri dijagnozi, gotovo 70% osoba s NSCLC ima lokalno uznapredovalu ili metastatsku bolest. Osobe s NSCLC često se liječe terapijskim spojevima platine (npr. cisplatinom, karboplatinom ili oksaliplatinom) koji uzrokuju međulančane unakrsne veze u DNK. Među osobama s NSCLC, niska ekspresija BRCA1 u primarnom tumoru korelirala je s poboljšanim preživljavanjem nakon hemoterapije koja sadrži platinu.[101][102] Ova korelacija implicira da nizak BRCA1 u karcinomu i posljedično nizak nivo popravljanja DNK uzrokuju ranjivost raka na liječenje pomoću DNK agenasa za umrežavanje. Visok BRCA1 može zaštititi ćelije raka, djelujući na put koji uklanja oštećenja u DNK koju unose lijekovi od platine. Stoga je nivo ekspresije BRCA1 potencijalno važan alat za prilagođavanje hemoterapije u upravljanju karcinomom pluća.

Nivo ekspresije BRCA1 je također važan za liječenje raka jajnika. Pacijenti sa sporadičnim karcinomom jajnika koji su liječeni lijekovima od platine imali su duže medijane vremena preživljavanja ako je njihova ekspresija BRCA1 bila niska u odnosu na pacijente sa jačom ekspresijom BRCA1 (46 u odnosu na 33 mjeseca).[103]

Interakcije

[uredi | uredi izvor]

Pokazalo se da BRCA1 komunicira sa sljedećim proteinima:

Reference

[uredi | uredi izvor]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000012048 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017146 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Hamel PJ (29. 5. 2007). "BRCA1 and BRCA2: No Longer the Only Troublesome Genes Out There". HealthCentral. Pristupljeno 2. 7. 2010.
  6. ^ a b "BRCA1 gene tree". Ensembl.
  7. ^ Duncan JA, Reeves JR, Cooke TG (oktobar 1998). "BRCA1 and BRCA2 proteins: roles in health and disease". Molecular Pathology. 51 (5): 237–47. doi:10.1136/mp.51.5.237. PMC 395646. PMID 10193517.
  8. ^ Yoshida K, Miki Y (novembar 2004). "Role of BRCA1 and BRCA2 as regulators of DNA repair, transcription, and cell cycle in response to DNA damage". Cancer Science. 95 (11): 866–71. doi:10.1111/j.1349-7006.2004.tb02195.x. PMID 15546503. S2CID 24297965.
  9. ^ Check W (1. 9. 2006). "BRCA: What we know now". College of American Pathologists. Pristupljeno 23. 8. 2010.
  10. ^ a b Irminger-Finger I, Ratajska M, Pilyugin M (2016). "New concepts on BARD1: Regulator of BRCA pathways and beyond". The International Journal of Biochemistry & Cell Biology. 72: 1–17. doi:10.1016/j.biocel.2015.12.008. PMID 26738429.
  11. ^ Friedenson B (august 2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer. 7: 152–162. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
  12. ^ Friedenson B (8. 6. 2008). "Breast cancer genes protect against some leukemias and lymphomas" (video). SciVee.
  13. ^ "Breast and Ovarian Cancer Genetic Screening". Palo Alto Medical Foundation. Arhivirano s originala, 4. 10. 2008. Pristupljeno 11. 10. 2008.
  14. ^ a b Friedenson B (2007). "The BRCA1/2 pathway prevents hematologic cancers in addition to breast and ovarian cancers". BMC Cancer. 7: 152. doi:10.1186/1471-2407-7-152. PMC 1959234. PMID 17683622.
  15. ^ O'Donovan PJ, Livingston DM (april 2010). "BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair". Carcinogenesis. 31 (6): 961–7. doi:10.1093/carcin/bgq069. PMID 20400477.
  16. ^ a b c d e f g Wang Y, Cortez D, Yazdi P, Neff N, Elledge SJ, Qin J (april 2000). "BASC, a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 (8): 927–39. doi:10.1101/gad.14.8.927 (neaktivno 31. 5. 2021). PMC 316544. PMID 10783165.CS1 održavanje: DOI nije aktivan od 2021 (link)
  17. ^ a b Starita LM, Parvin JD (2003). "The multiple nuclear functions of BRCA1: transcription, ubiquitination and DNA repair". Current Opinion in Cell Biology. 15 (3): 345–350. doi:10.1016/S0955-0674(03)00042-5. PMID 12787778.
  18. ^ Myriad Investor Page—see "Myriad at a glance" Arhivirano 18. 10. 2012. na Wayback Machine.
  19. ^ Webarchive|url=https://web.archive.org/web/20121018224334/http://investor.myriad.com/index.cfm |date=2012-10-18 }} accessed October 2012
  20. ^ Schwartz J (12. 5. 2009). "Cancer Patients Challenge the Patenting of a Gene". The New York Times. Health.
  21. ^ Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC (decembar 1990). "Linkage of early-onset familial breast cancer to chromosome 17q21". Science. 250 (4988): 1684–9. Bibcode:1990Sci...250.1684H. doi:10.1126/science.2270482. PMID 2270482.
  22. ^ High-Impact Science: Tracking down the BRCA genes (Part 1) Arhivirano 20. 2. 2016. na Wayback Machine – Cancer Research UK science blog, 2012
  23. ^ Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (oktobar 1994). "A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1". Science. 266 (5182): 66–71. Bibcode:1994Sci...266...66M. doi:10.1126/science.7545954. PMID 7545954.
  24. ^ (map).
  25. ^ [1]
  26. ^ Paterson JW (februar 1998). "BRCA1: a review of structure and putative functions". Dis. Markers. 13 (4): 261–74. doi:10.1155/1998/298530. PMID 9553742.
  27. ^ Henderson BR (septembar 2005). "Regulation of BRCA1, BRCA2 and BARD1 intracellular trafficking". BioEssays. 27 (9): 884–93. doi:10.1002/bies.20277. PMID 16108063. S2CID 10138907.
  28. ^ UniProt Full|P38398|Breast cancer type 1 susceptibility protein}}
  29. ^ Clark SL, Rodriguez AM, Snyder RR, Hankins GD, Boehning D (april 2012). "Structure-Function Of The Tumor Suppressor BRCA1". Comput Struct Biotechnol J. 1 (1): e201204005. doi:10.5936/csbj.201204005. PMC 3380633. PMID 22737296.
  30. ^ Sawyer SL, Tian L, Kahkonen M, Schwartzentruber J, Kircher M, Majewski J, Dyment DA, Innes AM, Boycott KM, Moreau LA, Moilanen JS, Greenberg RA (2014). "Biallelic Mutations in BRCA1 Cause a New Fanconi Anemia Subtype". Cancer Discov. 5 (2): 135–42. doi:10.1158/2159-8290.CD-14-1156. PMC 4320660. PMID 25472942.
  31. ^ "Kimball's Biologh Pages". Arhivirano s originala, 12. 2. 2018. Pristupljeno 23. 6. 2021.
  32. ^ Boulton SJ (novembar 2006). "Cellular functions of the BRCA tumour-suppressor proteins". Biochem. Soc. Trans. 34 (Pt 5): 633–45. doi:10.1042/BST0340633. PMID 17052168.
  33. ^ a b c d e f Wang Q, Zhang H, Guerrette S, Chen J, Mazurek A, Wilson T, Slupianek A, Skorski T, Fishel R, Greene MI (august 2001). "Adenosine nucleotide modulates the physical interaction between hMSH2 and BRCA1". Oncogene. 20 (34): 4640–9. doi:10.1038/sj.onc.1204625. PMID 11498787.
  34. ^ Warmoes M, Jaspers JE, Pham TV, Piersma SR, Oudgenoeg G, Massink MP, Waisfisz Q, Rottenberg S, Boven E, Jonkers J, Jimenez CR (juli 2012). "Proteomics of mouse BRCA1-deficient mammary tumors identifies DNA repair proteins with potential diagnostic and prognostic value in human breast cancer". Mol. Cell. Proteomics. 11 (7): M111.013334-1-M111.013334-19. doi:10.1074/mcp.M111.013334. PMC 3394939. PMID 22366898.
  35. ^ Meerang M, Ritz D, Paliwal S, Garajova Z, Bosshard M, Mailand N, Janscak P, Hübscher U, Meyer H, Ramadan K (novembar 2011). "The ubiquitin-selective segregase VCP/p97 orchestrates the response to DNA double-strand breaks". Nat. Cell Biol. 13 (11): 1376–82. doi:10.1038/ncb2367. PMID 22020440. S2CID 22109822.
  36. ^ Zhang H, Wang Q, Kajino K, Greene MI (2000). "VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells". DNA Cell Biol. 19 (5): 253–263. doi:10.1089/10445490050021168. PMID 10855792.
  37. ^ a b c Wang Q, Zhang H, Kajino K, Greene MI (oktobar 1998). "BRCA1 binds c-Myc and inhibits its transcriptional and transforming activity in cells". Oncogene. 17 (15): 1939–48. doi:10.1038/sj.onc.1202403. PMID 9788437.
  38. ^ Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (2001). "Direct DNA binding by Brca1". Proceedings of the National Academy of Sciences. 98 (11): 6086–6091. doi:10.1073/pnas.111125998. PMC 33426. PMID 11353843.
  39. ^ Durant ST, Nickoloff JA (2005). "Good timing in the cell cycle for precise DNA repair by BRCA1". Cell Cycle. 4 (9): 1216–22. doi:10.4161/cc.4.9.2027. PMID 16103751.
  40. ^ a b c d Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (2001). "BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations". The Journal of Cell Biology. 155 (6): 911–922. doi:10.1083/jcb.200108049. PMC 2150890. PMID 11739404.
  41. ^ Ridpath JR, Nakamura A, Tano K, Luke AM, Sonoda E, Arakawa H, Buerstedde JM, Gillespie DA, Sale JE, Yamazoe M, Bishop DK, Takata M, Takeda S, Watanabe M, Swenberg JA, Nakamura J (decembar 2007). "Cells deficient in the FANC/BRCA pathway are hypersensitive to plasma levels of formaldehyde". Cancer Res. 67 (23): 11117–22. doi:10.1158/0008-5472.CAN-07-3028. PMID 18056434.
  42. ^ Prakash R, Zhang Y, Feng W, Jasin M (april 2015). "Homologous recombination and human health: the roles of BRCA1, BRCA2, and associated proteins". Cold Spring Harbor Perspectives in Biology. 7 (4): a016600. doi:10.1101/cshperspect.a016600. PMC 4382744. PMID 25833843.
  43. ^ Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD (1997). "BRCA1 is a component of the RNA polymerase II holoenzyme". Proceedings of the National Academy of Sciences. 94 (11): 5605–10. Bibcode:1997PNAS...94.5605S. doi:10.1073/pnas.94.11.5605. PMC 20825. PMID 9159119.
  44. ^ Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F, Shiekhattar R (2000). "BRCA1 Is Associated with a Human SWI/SNF-Related Complex Linking Chromatin Remodeling to Breast Cancer". Cell. 102 (2): 257–265. doi:10.1016/S0092-8674(00)00030-1. PMID 10943845.
  45. ^ "Genetics". Breastcancer.org. 17. 9. 2012.
  46. ^ Mazoyer S (maj 2005). "Genomic rearrangements in the BRCA1 and BRCA2 genes". Hum. Mutat. 25 (5): 415–22. doi:10.1002/humu.20169. PMID 15832305. S2CID 32023181.
  47. ^ Barrois M, Bièche I, Mazoyer S, Champème MH, Bressac-de Paillerets B, Lidereau R (februar 2004). "Real-time PCR-based gene dosage assay for detecting BRCA1 rearrangements in breast-ovarian cancer families". Clin. Genet. 65 (2): 131–6. doi:10.1111/j.0009-9163.2004.00200.x. PMID 14984472. S2CID 11583160.
  48. ^ Hogervorst FB, Nederlof PM, Gille JJ, McElgunn CJ, Grippeling M, Pruntel R, Regnerus R, van Welsem T, van Spaendonk R, Menko FH, Kluijt I, Dommering C, Verhoef S, Schouten JP, van't Veer LJ, Pals G (april 2003). "Large genomic deletions and duplications in the BRCA1 gene identified by a novel quantitative method". Cancer Res. 63 (7): 1449–53. PMID 12670888.
  49. ^ Casilli F, Di Rocco ZC, Gad S, Tournier I, Stoppa-Lyonnet D, Frebourg T, Tosi M (septembar 2002). "Rapid detection of novel BRCA1 rearrangements in high-risk breast-ovarian cancer families using multiplex PCR of short fluorescent fragments". Hum. Mutat. 20 (3): 218–26. doi:10.1002/humu.10108. PMID 12203994. S2CID 24737909.
  50. ^ Rouleau E, Lefol C, Tozlu S, Andrieu C, Guy C, Copigny F, Nogues C, Bieche I, Lidereau R (septembar 2007). "High-resolution oligonucleotide array-CGH applied to the detection and characterization of large rearrangements in the hereditary breast cancer gene BRCA1". Clin. Genet. 72 (3): 199–207. doi:10.1111/j.1399-0004.2007.00849.x. PMID 17718857. S2CID 2393567.
  51. ^ Tapia T, Smalley SV, Kohen P, Muñoz A, Solis LM, Corvalan A, Faundez P, Devoto L, Camus M, Alvarez M, Carvallo P (2008). "Promoter hypermethylation of BRCA1 correlates with absence of expression in hereditary breast cancer tumors". Epigenetics. 3 (1): 157–63. doi:10.1186/bcr1858. PMID 18567944.
  52. ^ Shen J, Ambrosone CB, Zhao H (mart 2009). "Novel genetic variants in microRNA genes and familial breast cancer". Int. J. Cancer. 124 (5): 1178–82. doi:10.1002/ijc.24008. PMID 19048628.
  53. ^ Levin B, Lech D, Friedenson B (2012). "Evidence that BRCA1- or BRCA2-associated cancers are not inevitable". Mol Med. 18 (9): 1327–37. doi:10.2119/molmed.2012.00280. PMC 3521784. PMID 22972572.
  54. ^ Brody LC, Biesecker BB (1998). "Breast cancer susceptibility genes. BRCA1 and BRCA2". Medicine (Baltimore). 77 (3): 208–26. doi:10.1097/00005792-199805000-00006. PMID 9653432.
  55. ^ Pennington KP, Walsh T, Harrell MI, Lee MK, Pennil CC, Rendi MH, Thornton A, Norquist BM, Casadei S, Nord AS, Agnew KJ, Pritchard CC, Scroggins S, Garcia RL, King MC, Swisher EM (2014). "Germline and somatic mutations in homologous recombination genes predict platinum response and survival in ovarian, fallopian tube, and peritoneal carcinomas". Clin. Cancer Res. 20 (3): 764–75. doi:10.1158/1078-0432.CCR-13-2287. PMC 3944197. PMID 24240112.
  56. ^ Polansky H, Schwab H (august 2019). "How latent viruses cause breast cancer: An explanation based on the microcompetition model". Bosnian Journal of Basic Medical Sciences. 19 (3): 221–226. doi:10.17305/bjbms.2018.3950. PMC 6716096. PMID 30579323.
  57. ^ OMIM Entry Search - brca3
  58. ^ OMIM Entry - # 114480 - BREAST CANCER
  59. ^ https://omim.org/search?index=entry&sort=score desc, prefix_sort desc&start=1&limit=10&search=brca3
  60. ^ Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, Bussaglia E, Prat J, Harkes IC, Repasky EA, Gabrielson E, Schutte M, Baylin SB, Herman JG (2000). "Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors". J. Natl. Cancer Inst. 92 (7): 564–9. doi:10.1093/jnci/92.7.564. PMID 10749912.
  61. ^ Moskwa P, Buffa FM, Pan Y, Panchakshari R, Gottipati P, Muschel RJ, Beech J, Kulshrestha R, Abdelmohsen K, Weinstock DM, Gorospe M, Harris AL, Helleday T, Chowdhury D (2011). "miR-182-mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors". Mol. Cell. 41 (2): 210–20. doi:10.1016/j.molcel.2010.12.005. PMC 3249932. PMID 21195000.
  62. ^ Krishnan K, Steptoe AL, Martin HC, Wani S, Nones K, Waddell N, Mariasegaram M, Simpson PT, Lakhani SR, Gabrielli B, Vlassov A, Cloonan N, Grimmond SM (2013). "MicroRNA-182-5p targets a network of genes involved in DNA repair". RNA. 19 (2): 230–42. doi:10.1261/rna.034926.112. PMC 3543090. PMID 23249749.
  63. ^ Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS, Lidereau R, Mikaélian I, Mazoyer S (2011). "Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers". EMBO Mol Med. 3 (5): 279–90. doi:10.1002/emmm.201100136. PMC 3377076. PMID 21472990.
  64. ^ Kastan MB (2008). "DNA damage responses: mechanisms and roles in human disease: 2007 G.H.A. Clowes Memorial Award Lecture". Mol. Cancer Res. 6 (4): 517–24. doi:10.1158/1541-7786.MCR-08-0020. PMID 18403632.
  65. ^ Harper JW, Elledge SJ (2007). "The DNA damage response: ten years after". Mol. Cell. 28 (5): 739–45. doi:10.1016/j.molcel.2007.11.015. PMID 18082599.
  66. ^ O'Hagan HM, Mohammad HP, Baylin SB (2008). "Double strand breaks can initiate gene silencing and SIRT1-dependent onset of DNA methylation in an exogenous promoter CpG island". PLOS Genetics. 4 (8): e1000155. doi:10.1371/journal.pgen.1000155. PMC 2491723. PMID 18704159.
  67. ^ Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Di Pardo A, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, Avvedimento EV (Jul 2007). "DNA damage, homology-directed repair, and DNA methylation". PLOS Genetics. 3 (7): e110. doi:10.1371/journal.pgen.0030110. PMC 1913100. PMID 17616978.
  68. ^ den Dunnen JT, Antonarakis SE (2000). "Mutation nomenclature extensions and suggestions to describe complex mutations: a discussion". Human Mutation. 15 (1): 7–12. doi:10.1002/(SICI)1098-1004(200001)15:1<7::AID-HUMU4>3.0.CO;2-N. PMID 10612815.
  69. ^ a b Neuhausen SL (2000). "Founder populations and their uses for breast cancer genetics". Cancer Research. 2 (2): 77–81. doi:10.1186/bcr36. PMC 139426. PMID 11250694.
  70. ^ Reeves MD, Yawitch TM, van der Merwe NC, van den Berg HJ, Dreyer G, van Rensburg EJ (juli 2004). "BRCA1 mutations in South African breast and/or ovarian cancer families: evidence of a novel founder mutation in Afrikaner families". Int. J. Cancer. 110 (5): 677–82. doi:10.1002/ijc.20186. PMID 15146556. S2CID 22970255.
  71. ^ Francies FZ, Wainstein T, De Leeneer K, Cairns A, Murdoch M, Nietz S, Cubasch H, Poppe B, Van Maerken T, Crombez B, Coene I, Kerr R, Slabbert JP, Vral A, Krause A, Baeyens A (Nov 2015). "BRCA1, BRCA2 and PALB2 mutations and CHEK2 c.1100delC in different South African ethnic groups diagnosed with premenopausal and/or triple negative breast cancer". BMC Cancer. 15: 912. doi:10.1186/s12885-015-1913-6. PMC 4647511. PMID 26577449.
  72. ^ Tonin P, Serova O, Lenoir G, Lynch H, Durocher F, Simard J, Morgan K, Narod S (1995). "BRCA1 mutations in Ashkenazi Jewish women". American Journal of Human Genetics. 57 (1): 189. PMC 1801236. PMID 7611288.
  73. ^ Narod SA, Foulkes WD (2004). "BRCA1 and BRCA2: 1994 and beyond". Nature Reviews Cancer. 4 (9): 665–676. doi:10.1038/nrc1431. PMID 15343273. S2CID 30686068.
  74. ^ Wagner TM, Möslinger RA, Muhr D, Langbauer G, Hirtenlehner K, Concin H, Doeller W, Haid A, Lang AH, Mayer P, Ropp E, Kubista E, Amirimani B, Helbich T, Becherer A, Scheiner O, Breiteneder H, Borg A, Devilee P, Oefner P, Zielinski C (1998). "BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics". International Journal of Cancer. 77 (3): 354–360. doi:10.1002/(SICI)1097-0215(19980729)77:3<354::AID-IJC8>3.0.CO;2-N. PMID 9663595.
  75. ^ a b Peelen T, van Vliet M, Petrij-Bosch A, Mieremet R, Szabo C, van den Ouweland AM, Hogervorst F, Brohet R, Ligtenberg MJ, Teugels E, van der Luijt R, van der Hout AH, Gille JJ, Pals G, Jedema I, Olmer R, van Leeuwen I, Newman B, Plandsoen M, van der Est M, Brink G, Hageman S, Arts PJ, Bakker MM, Devilee P (1997). "A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families". American Journal of Human Genetics. 60 (5): 1041–1049. PMC 1712432. PMID 9150151.
  76. ^ Claes K, Machackova E, De Vos M, Poppe B, De Paepe A, Messiaen L (1999). "Mutation analysis of the BRCA1 and BRCA2 genes in the Belgian patient population and identification of a Belgian founder mutation BRCA1 IVS5 3A > G". Disease Markers. 15 (1–3): 69–73. doi:10.1155/1999/241046. PMC 3851655. PMID 10595255.
  77. ^ Petrij-Bosch A, Peelen T, van Vliet M, van Eijk R, Olmer R, Drüsedau M, Hogervorst FB, Hageman S, Arts PJ, Ligtenberg MJ, Meijers-Heijboer H, Klijn JG, Vasen HF, Cornelisse CJ, van 't Veer LJ, Bakker E, van Ommen GJ, Devilee P (1997). "BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients" (PDF). Nature Genetics. 17 (3): 341–345. doi:10.1038/ng1197-341. hdl:1765/54808. PMID 9354803. S2CID 13028232.
  78. ^ Verhoog LC, van den Ouweland AM, Berns E, van Veghel-Plandsoen MM, van Staveren IL, Wagner A, Bartels CC, Tilanus-Linthorst MM, Devilee P, Seynaeve C, Halley DJ, Niermeijer MF, Klijn JG, Meijers-Heijboer H (2001). "Large regional differences in the frequency of distinct BRCA1/BRCA2 mutations in 517 Dutch breast and/or ovarian cancer families". European Journal of Cancer. 37 (16): 2082–2090. doi:10.1016/S0959-8049(01)00244-1. PMID 11597388.
  79. ^ Huusko P, Pääkkönen K, Launonen V, Pöyhönen M, Blanco G, Kauppila A, Puistola U, Kiviniemi H, Kujala M, Leisti J, Winqvist R (1998). "Evidence of founder mutations in Finnish BRCA1 and BRCA2 families". American Journal of Human Genetics. 62 (6): 1544–1548. doi:10.1086/301880. PMC 1377159. PMID 9585608.
  80. ^ Pääkkönen K, Sauramo S, Sarantaus L, Vahteristo P, Hartikainen A, Vehmanen P, Ignatius J, Ollikainen V, Kääriäinen H, Vauramo E, Nevanlinna H, Krahe R, Holli K, Kere J (2001). "Involvement of BRCA1 and BRCA2 in breast cancer in a western Finnish sub-population". Genetic Epidemiology. 20 (2): 239–246. doi:10.1002/1098-2272(200102)20:2<239::AID-GEPI6>3.0.CO;2-Y. PMID 11180449.
  81. ^ Muller D, Bonaiti-Pellié C, Abecassis J, Stoppa-Lyonnet D, Fricker JP (2004). "BRCA1 testing in breast and/or ovarian cancer families from northeastern France identifies two common mutations with a founder effect". Familial Cancer. 3 (1): 15–20. doi:10.1023/B:FAME.0000026819.44213.df. PMID 15131401. S2CID 24615109.
  82. ^ Tonin PN, Mes-Masson AM, Narod SA, Ghadirian P, Provencher D (1999). "Founder BRCA1 and BRCA2 mutations in French Canadian ovarian cancer cases unselected for family history". Clinical Genetics. 55 (5): 318–324. doi:10.1034/j.1399-0004.1999.550504.x. PMID 10422801. S2CID 23931343.
  83. ^ Backe J, Hofferbert S, Skawran B, Dörk T, Stuhrmann M, Karstens JH, Untch M, Meindl A, Burgemeister R, Chang-Claude J, Weber BH (1999). "Frequency of BRCA1 mutation 5382insC in German breast cancer patients". Gynecologic Oncology. 72 (3): 402–406. doi:10.1006/gyno.1998.5270. PMID 10053113.
  84. ^ "Mutation data of the BRCA1 gene". KMDB/MutationView (Keio Mutation Databases). Keio University.
  85. ^ Ladopoulou A, Kroupis C, Konstantopoulou I, Ioannidou-Mouzaka L, Schofield AC, Pantazidis A, Armaou S, Tsiagas I, Lianidou E, Efstathiou E, Tsionou C, Panopoulos C, Mihalatos M, Nasioulas G, Skarlos D, Haites NE, Fountzilas G, Pandis N, Yannoukakos D (2002). "Germ line BRCA1 and BRCA2 mutations in Greek breast/ovarian cancer families: 5382insC is the most frequent mutation observed". Cancer Letters. 185 (1): 61–70. doi:10.1016/S0304-3835(01)00845-X. PMID 12142080.
  86. ^ Van Der Looij M, Szabo C, Besznyak I, Liszka G, Csokay B, Pulay T, Toth J, Devilee P, King MC, Olah E (2000). "Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary". International Journal of Cancer. 86 (5): 737–740. doi:10.1002/(SICI)1097-0215(20000601)86:5<737::AID-IJC21>3.0.CO;2-1. PMID 10797299.
  87. ^ Baudi F, Quaresima B, Grandinetti C, Cuda G, Faniello C, Tassone P, Barbieri V, Bisegna R, Ricevuto E, Conforti S, Viel A, Marchetti P, Ficorella C, Radice P, Costanzo F, Venuta S (2001). "Evidence of a founder mutation of BRCA1 in a highly homogeneous population from southern Italy with breast/ovarian cancer". Human Mutation. 18 (2): 163–164. doi:10.1002/humu.1167. PMID 11462242. S2CID 2995.
  88. ^ Sekine M, Nagata H, Tsuji S, Hirai Y, Fujimoto S, Hatae M, Kobayashi I, Fujii T, Nagata I, Ushijima K, Obata K, Suzuki M, Yoshinaga M, Umesaki N, Satoh S, Enomoto T, Motoyama S, Tanaka K (2001). "Mutational analysis of BRCA1 and BRCA2 and clinicopathologic analysis of ovarian cancer in 82 ovarian cancer families: two common founder mutations of BRCA1 in Japanese population". Clinical Cancer Research. 7 (10): 3144–3150. PMID 11595708.
  89. ^ Liede A, Jack E, Hegele RA, Narod SA (2002). "A BRCA1 mutation in Native North American families". Human Mutation. 19 (4): 460. doi:10.1002/humu.9027. PMID 11933205. S2CID 37710898.
  90. ^ a b The Scottish/Northern Irish BRCA1/BRCA2 Consortium (2003). "BRCA1 and BRCA2 mutations in Scotland and Northern Ireland". British Journal of Cancer. 88 (8): 1256–1262. doi:10.1038/sj.bjc.6600840. PMC 2747571. PMID 12698193.
  91. ^ Borg A, Dørum A, Heimdal K, Maehle L, Hovig E, Møller P (1999). "BRCA1 1675delA and 1135insA account for one third of Norwegian familial breast-ovarian cancer and are associated with later disease onset than less frequent mutations". Disease Markers. 15 (1–3): 79–84. doi:10.1155/1999/278269. PMC 3851406. PMID 10595257.
  92. ^ Heimdal K, Maehle L, Apold J, Pedersen JC, Møller P (2003). "The Norwegian founder mutations in BRCA1: high penetrance confirmed in an incident cancer series and differences observed in the risk of ovarian cancer". European Journal of Cancer. 39 (15): 2205–2213. doi:10.1016/S0959-8049(03)00548-3. PMID 14522380.
  93. ^ Liede A, Malik IA, Aziz Z, Rios Pd Pde L, Kwan E, Narod SA (2002). "Contribution of BRCA1 and BRCA2 Mutations to Breast and Ovarian Cancer in Pakistan". American Journal of Human Genetics. 71 (3): 595–606. doi:10.1086/342506. PMC 379195. PMID 12181777.
  94. ^ Górski B, Byrski T, Huzarski T, Jakubowska A, Menkiszak J, Gronwald J, Pluzańska A, Bebenek M, Fischer-Maliszewska L, Grzybowska E, Narod SA, Lubiński J (2000). "Founder mutations in the BRCA1 gene in Polish families with breast-ovarian cancer". American Journal of Human Genetics. 66 (6): 1963–1968. doi:10.1086/302922. PMC 1378051. PMID 10788334.
  95. ^ Perkowska M, BroZek I, Wysocka B, Haraldsson K, Sandberg T, Johansson U, Sellberg G, Borg A, Limon J (maj 2003). "BRCA1 and BRCA2 mutation analysis in breast-ovarian cancer families from northeastern Poland". Hum. Mutat. 21 (5): 553–4. doi:10.1002/humu.9139. PMID 12673801. S2CID 7001156.
  96. ^ Gayther SA, Harrington P, Russell P, Kharkevich G, Garkavtseva RF, Ponder BA (maj 1997). "Frequently occurring germ-line mutations of the BRCA1 gene in ovarian cancer families from Russia". Am. J. Hum. Genet. 60 (5): 1239–42. PMC 1712436. PMID 9150173.
  97. ^ Liede A, Cohen B, Black DM, Davidson RH, Renwick A, Hoodfar E, Olopade OI, Micek M, Anderson V, De Mey R, Fordyce A, Warner E, Dann JL, King MC, Weber B, Narod SA, Steel CM (februar 2000). "Evidence of a founder BRCA1 mutation in Scotland". Br. J. Cancer. 82 (3): 705–11. doi:10.1054/bjoc.1999.0984. PMC 2363321. PMID 10682686.
  98. ^ Vega A, Campos B, Bressac-De-Paillerets B, Bond PM, Janin N, Douglas FS, Domènech M, Baena M, Pericay C, Alonso C, Carracedo A, Baiget M, Diez O (juni 2001). "The R71G BRCA1 is a founder Spanish mutation and leads to aberrant splicing of the transcript". Hum. Mutat. 17 (6): 520–1. doi:10.1002/humu.1136. PMID 11385711. S2CID 39462456.
  99. ^ Campos B, Díez O, Odefrey F, Domènech M, Moncoutier V, Martínez-Ferrandis JI, Osorio A, Balmaña J, Barroso A, Armengod ME, Benítez J, Alonso C, Stoppa-Lyonnet D, Goldgar D, Baiget M (april 2003). "Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain". Hum. Mutat. 21 (4): 452. doi:10.1002/humu.9133. PMID 12655574. S2CID 34333797.
  100. ^ Bergman A, Einbeigi Z, Olofsson U, Taib Z, Wallgren A, Karlsson P, Wahlström J, Martinsson T, Nordling M (oktobar 2001). "The western Swedish BRCA1 founder mutation 3171ins5; a 3.7 cM conserved haplotype of today is a reminiscence of a 1500-year-old mutation". Eur. J. Hum. Genet. 9 (10): 787–93. doi:10.1038/sj.ejhg.5200704. PMID 11781691.
  101. ^ Taron M, Rosell R, Felip E, Mendez P, Souglakos J, Ronco MS, Queralt C, Majo J, Sanchez JM, Sanchez JJ, Maestre J (oktobar 2004). "BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer". Hum. Mol. Genet. 13 (20): 2443–9. doi:10.1093/hmg/ddh260. PMID 15317748.
  102. ^ Papadaki C, Sfakianaki M, Ioannidis G, Lagoudaki E, Trypaki M, Tryfonidis K, Mavroudis D, Stathopoulos E, Georgoulias V, Souglakos J (april 2012). "ERCC1 and BRAC1 mRNA expression levels in the primary tumor could predict the effectiveness of the second-line cisplatin-based chemotherapy in pretreated patients with metastatic non-small cell lung cancer". J Thorac Oncol. 7 (4): 663–71. doi:10.1097/JTO.0b013e318244bdd4. PMID 22425915.
  103. ^ Weberpals J, Garbuio K, O'Brien A, Clark-Knowles K, Doucette S, Antoniouk O, Goss G, Dimitroulakos J (februar 2009). "The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer". Int. J. Cancer. 124 (4): 806–15. doi:10.1002/ijc.23987. PMID 19035454. S2CID 13357407.
  104. ^ Foray N, Marot D, Randrianarison V, Venezia ND, Picard D, Perricaudet M, Favaudon V, Jeggo P (juni 2002). "Constitutive association of BRCA1 and c-Abl and its ATM-dependent disruption after irradiation". Mol. Cell. Biol. 22 (12): 4020–32. doi:10.1128/MCB.22.12.4020-4032.2002. PMC 133860. PMID 12024016.
  105. ^ Altiok S, Batt D, Altiok N, Papautsky A, Downward J, Roberts TM, Avraham H (novembar 1999). "Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-Kinase/AKT in breast cancer cells". J. Biol. Chem. 274 (45): 32274–8. doi:10.1074/jbc.274.45.32274. PMID 10542266.
  106. ^ Xiang T, Ohashi A, Huang Y, Pandita TK, Ludwig T, Powell SN, Yang Q (decembar 2008). "Negative Regulation of AKT Activation by BRCA1". Cancer Res. 68 (24): 10040–4. doi:10.1158/0008-5472.CAN-08-3009. PMC 2605656. PMID 19074868.
  107. ^ Yeh S, Hu YC, Rahman M, Lin HK, Hsu CL, Ting HJ, Kang HY, Chang C (oktobar 2000). "Increase of androgen-induced cell death and androgen receptor transactivation by BRCA1 in prostate cancer cells". Proc. Natl. Acad. Sci. U.S.A. 97 (21): 11256–61. Bibcode:2000PNAS...9711256Y. doi:10.1073/pnas.190353897. PMC 17187. PMID 11016951.
  108. ^ a b Kim ST, Lim DS, Canman CE, Kastan MB (decembar 1999). "Substrate specificities and identification of putative substrates of ATM kinase family members". J. Biol. Chem. 274 (53): 37538–43. doi:10.1074/jbc.274.53.37538. PMID 10608806.
  109. ^ a b Tibbetts RS, Cortez D, Brumbaugh KM, Scully R, Livingston D, Elledge SJ, Abraham RT (decembar 2000). "Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress". Genes Dev. 14 (23): 2989–3002. doi:10.1101/gad.851000. PMC 317107. PMID 11114888.
  110. ^ a b Chen J (septembar 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage". Cancer Res. 60 (18): 5037–9. PMID 11016625.
  111. ^ a b Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (maj 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 related kinase mediate phosphorylation of Brca1 at distinct and overlapping sites. In vivo assessment using phospho-specific antibodies". J. Biol. Chem. 276 (20): 17276–80. doi:10.1074/jbc.M011681200. PMID 11278964.
  112. ^ Gatei M, Scott SP, Filippovitch I, Soronika N, Lavin MF, Weber B, Khanna KK (juni 2000). "Role for ATM in DNA damage-induced phosphorylation of BRCA1". Cancer Res. 60 (12): 3299–304. PMID 10866324.
  113. ^ Cortez D, Wang Y, Qin J, Elledge SJ (novembar 1999). "Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks". Science. 286 (5442): 1162–6. doi:10.1126/science.286.5442.1162. PMID 10550055.
  114. ^ Houvras Y, Benezra M, Zhang H, Manfredi JJ, Weber BL, Licht JD (novembar 2000). "BRCA1 physically and functionally interacts with ATF1". J. Biol. Chem. 275 (46): 36230–7. doi:10.1074/jbc.M002539200. PMID 10945975.
  115. ^ a b Cantor SB, Bell DW, Ganesan S, Kass EM, Drapkin R, Grossman S, Wahrer DC, Sgroi DC, Lane WS, Haber DA, Livingston DM (april 2001). "BACH1, a novel helicase-like protein, interacts directly with BRCA1 and contributes to its DNA repair function". Cell. 105 (1): 149–60. doi:10.1016/S0092-8674(01)00304-X. PMID 11301010.
  116. ^ a b c d e f Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R (novembar 2003). "Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair". Mol. Cell. 12 (5): 1087–99. doi:10.1016/S1097-2765(03)00424-6. PMID 14636569.
  117. ^ a b Chen J, Silver DP, Walpita D, Cantor SB, Gazdar AF, Tomlinson G, Couch FJ, Weber BL, Ashley T, Livingston DM, Scully R (septembar 1998). "Stable interaction between the products of the BRCA1 and BRCA2 tumor suppressor genes in mitotic and meiotic cells". Mol. Cell. 2 (3): 317–28. doi:10.1016/S1097-2765(00)80276-2. PMID 9774970.
  118. ^ a b Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (oktobar 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
  119. ^ Sarkisian CJ, Master SR, Huber LJ, Ha SI, Chodosh LA (oktobar 2001). "Analysis of murine Brca2 reveals conservation of protein–protein interactions but differences in nuclear localization signals". J. Biol. Chem. 276 (40): 37640–8. doi:10.1074/jbc.M106281200. PMID 11477095.
  120. ^ a b c d Rodriguez M, Yu X, Chen J, Songyang Z (decembar 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. Biol. Chem. 278 (52): 52914–8. doi:10.1074/jbc.C300407200. PMID 14578343.
  121. ^ a b c d Wada O, Oishi H, Takada I, Yanagisawa J, Yano T, Kato S (august 2004). "BRCA1 function mediates a TRAP/DRIP complex through direct interaction with TRAP220". Oncogene. 23 (35): 6000–5. doi:10.1038/sj.onc.1207786. PMID 15208681.
  122. ^ Botuyan MV, Nominé Y, Yu X, Juranic N, Macura S, Chen J, Mer G (juli 2004). "Structural basis of BACH1 phosphopeptide recognition by BRCA1 tandem BRCT domains". Structure. 12 (7): 1137–46. doi:10.1016/j.str.2004.06.002. PMC 3652423. PMID 15242590.
  123. ^ Yu X, Chini CC, He M, Mer G, Chen J (oktobar 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639–42. Bibcode:2003Sci...302..639Y. doi:10.1126/science.1088753. PMID 14576433. S2CID 29407635.
  124. ^ Clapperton JA, Manke IA, Lowery DM, Ho T, Haire LF, Yaffe MB, Smerdon SJ (juni 2004). "Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer". Nature Structural & Molecular Biology. 11 (6): 512–8. doi:10.1038/nsmb775. PMID 15133502. S2CID 7354915.
  125. ^ a b c Hu YF, Li R (juni 2002). "JunB potentiates function of BRCA1 activation domain 1 (AD1) through a coiled-coil-mediated interaction". Genes Dev. 16 (12): 1509–17. doi:10.1101/gad.995502. PMC 186344. PMID 12080089.
  126. ^ Lee JS, Collins KM, Brown AL, Lee CH, Chung JH (mart 2000). "hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response". Nature. 404 (6774): 201–4. Bibcode:2000Natur.404..201L. doi:10.1038/35004614. PMID 10724175. S2CID 4345911.
  127. ^ Chabalier-Taste C, Racca C, Dozier C, Larminat F (decembar 2008). "BRCA1 is regulated by Chk2 in response to spindle damage". Biochim. Biophys. Acta. 1783 (12): 2223–33. doi:10.1016/j.bbamcr.2008.08.006. PMID 18804494.
  128. ^ Lin SY, Li K, Stewart GS, Elledge SJ (april 2004). "Human Claspin works with BRCA1 to both positively and negatively regulate cell proliferation". Proc. Natl. Acad. Sci. U.S.A. 101 (17): 6484–9. Bibcode:2004PNAS..101.6484L. doi:10.1073/pnas.0401847101. PMC 404071. PMID 15096610.
  129. ^ Ye Q, Hu YF, Zhong H, Nye AC, Belmont AS, Li R (decembar 2001). "BRCA1-induced large-scale chromatin unfolding and allele-specific effects of cancer-predisposing mutations". J. Cell Biol. 155 (6): 911–21. doi:10.1083/jcb.200108049. PMC 2150890. PMID 11739404.
  130. ^ a b Benezra M, Chevallier N, Morrison DJ, MacLachlan TK, El-Deiry WS, Licht JD (juli 2003). "BRCA1 augments transcription by the NF-kappaB transcription factor by binding to the Rel domain of the p65/RelA subunit". J. Biol. Chem. 278 (29): 26333–41. doi:10.1074/jbc.M303076200. PMID 12700228.
  131. ^ a b Pao GM, Janknecht R, Ruffner H, Hunter T, Verma IM (februar 2000). "CBP/p300 interact with and function as transcriptional coactivators of BRCA1". Proc. Natl. Acad. Sci. U.S.A. 97 (3): 1020–5. Bibcode:2000PNAS...97.1020P. doi:10.1073/pnas.97.3.1020. PMC 15508. PMID 10655477.
  132. ^ a b Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN (januar 1999). "The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter". Oncogene. 18 (1): 263–8. doi:10.1038/sj.onc.1202323. PMID 9926942.
  133. ^ a b c Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM (januar 2002). "p300 Modulates the BRCA1 inhibition of estrogen receptor activity". Cancer Res. 62 (1): 141–51. PMID 11782371.
  134. ^ Neish AS, Anderson SF, Schlegel BP, Wei W, Parvin JD (februar 1998). "Factors associated with the mammalian RNA polymerase II holoenzyme". Nucleic Acids Res. 26 (3): 847–53. doi:10.1093/nar/26.3.847. PMC 147327. PMID 9443979.
  135. ^ O'Brien KA, Lemke SJ, Cocke KS, Rao RN, Beckmann RP (juli 1999). "Casein kinase 2 binds to and phosphorylates BRCA1". Biochem. Biophys. Res. Commun. 260 (3): 658–64. doi:10.1006/bbrc.1999.0892. PMID 10403822.
  136. ^ Kleiman FE, Manley JL (mart 2001). "The BARD1-CstF-50 interaction links mRNA 3' end formation to DNA damage and tumor suppression". Cell. 104 (5): 743–53. doi:10.1016/S0092-8674(01)00270-7. PMID 11257228.
  137. ^ Kleiman FE, Manley JL (septembar 1999). "Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50". Science. 285 (5433): 1576–9. doi:10.1126/science.285.5433.1576. PMID 10477523.
  138. ^ Wang H, Shao N, Ding QM, Cui J, Reddy ES, Rao VN (Jul 1997). "BRCA1 proteins are transported to the nucleus in the absence of serum and splice variants BRCA1a, BRCA1b are tyrosine phosphoproteins that associate with E2F, cyclins and cyclin dependent kinases". Oncogene. 15 (2): 143–57. doi:10.1038/sj.onc.1201252. PMID 9244350.
  139. ^ Chen Y, Farmer AA, Chen CF, Jones DC, Chen PL, Lee WH (juli 1996). "BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner". Cancer Res. 56 (14): 3168–72. PMID 8764100.
  140. ^ Ruffner H, Jiang W, Craig AG, Hunter T, Verma IM (juli 1999). "BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2 phosphorylation site". Mol. Cell. Biol. 19 (7): 4843–54. doi:10.1128/MCB.19.7.4843. PMC 84283. PMID 10373534.
  141. ^ Schlegel BP, Starita LM, Parvin JD (februar 2003). "Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and cytokinesis in mammary epithelial cells". Oncogene. 22 (7): 983–91. doi:10.1038/sj.onc.1206195. PMID 12592385.
  142. ^ Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD (juli 1998). "BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A". Nat. Genet. 19 (3): 254–6. doi:10.1038/930. PMID 9662397. S2CID 10953768.
  143. ^ Chai Y, Chipitsyna G, Cui J, Liao B, Liu S, Aysola K, Yezdani M, Reddy ES, Rao VN (mart 2001). "c-Fos oncogene regulator Elk-1 interacts with BRCA1 splice variants BRCA1a/1b and enhances BRCA1a/1b-mediated growth suppression in breast cancer cells". Oncogene. 20 (11): 1357–67. doi:10.1038/sj.onc.1204256. PMID 11313879.
  144. ^ Zheng L, Annab LA, Afshari CA, Lee WH, Boyer TG (august 2001). "BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor". Proc. Natl. Acad. Sci. U.S.A. 98 (17): 9587–92. Bibcode:2001PNAS...98.9587Z. doi:10.1073/pnas.171174298. PMC 55496. PMID 11493692.
  145. ^ Fan S, Ma YX, Wang C, Yuan RQ, Meng Q, Wang JA, Erdos M, Goldberg ID, Webb P, Kushner PJ, Pestell RG, Rosen EM (januar 2001). "Role of direct interaction in BRCA1 inhibition of estrogen receptor activity". Oncogene. 20 (1): 77–87. doi:10.1038/sj.onc.1204073. PMID 11244506.
  146. ^ Kawai H, Li H, Chun P, Avraham S, Avraham HK (oktobar 2002). "Direct interaction between BRCA1 and the estrogen receptor regulates vascular endothelial growth factor (VEGF) transcription and secretion in breast cancer cells". Oncogene. 21 (50): 7730–9. doi:10.1038/sj.onc.1205971. PMID 12400015.
  147. ^ Folias A, Matkovic M, Bruun D, Reid S, Hejna J, Grompe M, D'Andrea A, Moses R (oktobar 2002). "BRCA1 interacts directly with the Fanconi anemia protein FANCA". Hum. Mol. Genet. 11 (21): 2591–7. doi:10.1093/hmg/11.21.2591. PMID 12354784.
  148. ^ a b Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ (juli 2003). "BRCA1-independent ubiquitination of FANCD2". Mol. Cell. 12 (1): 247–54. doi:10.1016/S1097-2765(03)00281-8. PMID 12887909.
  149. ^ Yan J, Zhu J, Zhong H, Lu Q, Huang C, Ye Q (oktobar 2003). "BRCA1 interacts with FHL2 and enhances FHL2 transactivation function". FEBS Lett. 553 (1–2): 183–9. doi:10.1016/S0014-5793(03)00978-5. PMID 14550570. S2CID 31566004.
  150. ^ Yan JH, Ye QN, Zhu JH, Zhong HJ, Zheng HY, Huang CF (decembar 2003). "[Isolation and characterization of a BRCA1-interacting protein]". Yi Chuan Xue Bao (jezik: kineski). 30 (12): 1161–6. PMID 14986435.
  151. ^ a b Mallery DL, Vandenberg CJ, Hiom K (decembar 2002). "Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains". EMBO J. 21 (24): 6755–62. doi:10.1093/emboj/cdf691. PMC 139111. PMID 12485996.
  152. ^ a b Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ (juni 2002). "Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase". J. Biol. Chem. 277 (24): 22085–92. doi:10.1074/jbc.M201252200. PMID 11927591.
  153. ^ Paull TT, Rogakou EP, Yamazaki V, Kirchgessner CU, Gellert M, Bonner WM (2000). "A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage". Curr. Biol. 10 (15): 886–95. doi:10.1016/S0960-9822(00)00610-2. PMID 10959836.
  154. ^ Sutherland KD, Visvader JE, Choong DY, Sum EY, Lindeman GJ, Campbell IG (oktobar 2003). "Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas". Int. J. Cancer. 107 (1): 155–8. doi:10.1002/ijc.11343. PMID 12925972. S2CID 20908722.
  155. ^ Sum EY, Peng B, Yu X, Chen J, Byrne J, Lindeman GJ, Visvader JE (mart 2002). "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. Biol. Chem. 277 (10): 7849–56. doi:10.1074/jbc.M110603200. PMID 11751867.
  156. ^ Gilmore PM, McCabe N, Quinn JE, Kennedy RD, Gorski JJ, Andrews HN, McWilliams S, Carty M, Mullan PB, Duprex WP, Liu ET, Johnston PG, Harkin DP (juni 2004). "BRCA1 interacts with and is required for paclitaxel-induced activation of mitogen-activated protein kinase kinase kinase 3". Cancer Res. 64 (12): 4148–54. doi:10.1158/0008-5472.CAN-03-4080. PMID 15205325.
  157. ^ a b c d e Chiba N, Parvin JD (oktobar 2001). "Redistribution of BRCA1 among four different protein complexes following replication blockage". J. Biol. Chem. 276 (42): 38549–54. doi:10.1074/jbc.M105227200. PMID 11504724.
  158. ^ Chiba N, Parvin JD (august 2002). "The BRCA1 and BARD1 association with the RNA polymerase II holoenzyme". Cancer Res. 62 (15): 4222–8. PMID 12154023.
  159. ^ a b Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD (maj 1997). "BRCA1 is a component of the RNA polymerase II holoenzyme". Proc. Natl. Acad. Sci. U.S.A. 94 (11): 5605–10. Bibcode:1997PNAS...94.5605S. doi:10.1073/pnas.94.11.5605. PMC 20825. PMID 9159119.
  160. ^ a b c Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (juli 1999). "Association of BRCA1 with the hRad50-hMre11-p95 complex and the DNA damage response". Science. 285 (5428): 747–50. doi:10.1126/science.285.5428.747. PMID 10426999.
  161. ^ Paull TT, Cortez D, Bowers B, Elledge SJ, Gellert M (maj 2001). "Direct DNA binding by Brca1". Proc. Natl. Acad. Sci. U.S.A. 98 (11): 6086–91. doi:10.1073/pnas.111125998. PMC 33426. PMID 11353843.
  162. ^ a b Li H, Lee TH, Avraham H (juni 2002). "A novel tricomplex of BRCA1, Nmi, and c-Myc inhibits c-Myc-induced human telomerase reverse transcriptase gene (hTERT) promoter activity in breast cancer". J. Biol. Chem. 277 (23): 20965–73. doi:10.1074/jbc.M112231200. PMID 11916966.
  163. ^ Xiong J, Fan S, Meng Q, Schramm L, Wang C, Bouzahza B, Zhou J, Zafonte B, Goldberg ID, Haddad BR, Pestell RG, Rosen EM (decembar 2003). "BRCA1 inhibition of telomerase activity in cultured cells". Mol. Cell. Biol. 23 (23): 8668–90. doi:10.1128/MCB.23.23.8668-8690.2003. PMC 262673. PMID 14612409.
  164. ^ Zhou C, Liu J (mart 2003). "Inhibition of human telomerase reverse transcriptase gene expression by BRCA1 in human ovarian cancer cells". Biochem. Biophys. Res. Commun. 303 (1): 130–6. doi:10.1016/S0006-291X(03)00318-8. PMID 12646176.
  165. ^ a b Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T (juli 2004). "Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (30): 30919–22. doi:10.1074/jbc.C400169200. PMID 15184379.
  166. ^ Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA (novembar 2000). "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 8636–9. PMID 11085509.
  167. ^ Cabart P, Chew HK, Murphy S (juli 2004). "BRCA1 cooperates with NUFIP and P-TEFb to activate transcription by RNA polymerase II". Oncogene. 23 (31): 5316–29. doi:10.1038/sj.onc.1207684. PMID 15107825.
  168. ^ Abramovitch S, Werner H (2003). "Functional and physical interactions between BRCA1 and p53 in transcriptional regulation of the IGF-IR gene". Horm. Metab. Res. 35 (11–12): 758–62. doi:10.1055/s-2004-814154. PMID 14710355.
  169. ^ Ouchi T, Monteiro AN, August A, Aaronson SA, Hanafusa H (mart 1998). "BRCA1 regulates p53-dependent gene expression". Proc. Natl. Acad. Sci. U.S.A. 95 (5): 2302–6. Bibcode:1998PNAS...95.2302O. doi:10.1073/pnas.95.5.2302. PMC 19327. PMID 9482880.
  170. ^ Zhang H, Somasundaram K, Peng Y, Tian H, Zhang H, Bi D, Weber BL, El-Deiry WS (april 1998). "BRCA1 physically associates with p53 and stimulates its transcriptional activity". Oncogene. 16 (13): 1713–21. doi:10.1038/sj.onc.1201932. PMID 9582019.
  171. ^ Sy SM, Huen MS, Chen J (april 2009). "PALB2 is an integral component of the BRCA complex required for homologous recombination repair". Proc. Natl. Acad. Sci. U.S.A. 106 (17): 7155–60. Bibcode:2009PNAS..106.7155S. doi:10.1073/pnas.0811159106. PMC 2678481. PMID 19369211.
  172. ^ Krum SA, Miranda GA, Lin C, Lane TF (decembar 2003). "BRCA1 associates with processive RNA polymerase II". J. Biol. Chem. 278 (52): 52012–20. doi:10.1074/jbc.M308418200. PMID 14506230.
  173. ^ Krum SA, Womack JE, Lane TF (septembar 2003). "Bovine BRCA1 shows classic responses to genotoxic stress but low in vitro transcriptional activation activity". Oncogene. 22 (38): 6032–44. doi:10.1038/sj.onc.1206515. PMID 12955082.
  174. ^ Liu Y, Virshup DM, White RL, Hsu LC (novembar 2002). "Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha". Cancer Res. 62 (22): 6357–61. PMID 12438214.
  175. ^ Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM (januar 1997). "Association of BRCA1 with Rad51 in mitotic and meiotic cells". Cell. 88 (2): 265–75. doi:10.1016/S0092-8674(00)81847-4. PMID 9008167.
  176. ^ a b c Yarden RI, Brody LC (april 1999). "BRCA1 interacts with components of the histone deacetylase complex". Proc. Natl. Acad. Sci. U.S.A. 96 (9): 4983–8. Bibcode:1999PNAS...96.4983Y. doi:10.1073/pnas.96.9.4983. PMC 21803. PMID 10220405.
  177. ^ Chen GC, Guan LS, Yu JH, Li GC, Choi Kim HR, Wang ZY (juni 2001). "Rb-associated protein 46 (RbAp46) inhibits transcriptional transactivation mediated by BRCA1". Biochem. Biophys. Res. Commun. 284 (2): 507–14. doi:10.1006/bbrc.2001.5003. PMID 11394910.
  178. ^ a b Yarden RI, Brody LC (2001). "Identification of proteins that interact with BRCA1 by Far-Western library screening". J. Cell. Biochem. 83 (4): 521–31. doi:10.1002/jcb.1257. PMID 11746496. S2CID 29703139.
  179. ^ Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (septembar 1998). "The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a protein implicated in the CtBP pathway of transcriptional repression". J. Biol. Chem. 273 (39): 25388–92. doi:10.1074/jbc.273.39.25388. PMID 9738006.
  180. ^ Li S, Chen PL, Subramanian T, Chinnadurai G, Tomlinson G, Osborne CK, Sharp ZD, Lee WH (april 1999). "Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage". J. Biol. Chem. 274 (16): 11334–8. doi:10.1074/jbc.274.16.11334. PMID 10196224.
  181. ^ Wong AK, Ormonde PA, Pero R, Chen Y, Lian L, Salada G, Berry S, Lawrence Q, Dayananth P, Ha P, Tavtigian SV, Teng DH, Bartel PL (novembar 1998). "Characterization of a carboxy-terminal BRCA1 interacting protein". Oncogene. 17 (18): 2279–85. doi:10.1038/sj.onc.1202150. PMID 9811458.
  182. ^ Li S, Ting NS, Zheng L, Chen PL, Ziv Y, Shiloh Y, Lee EY, Lee WH (juli 2000). "Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response". Nature. 406 (6792): 210–5. Bibcode:2000Natur.406..210L. doi:10.1038/35018134. PMID 10910365. S2CID 3266654.
  183. ^ Wu-Baer F, Baer R (novembar 2001). "Effect of DNA damage on a BRCA1 complex". Nature. 414 (6859): 36. doi:10.1038/35102118. PMID 11689934. S2CID 4329675.
  184. ^ Yu X, Baer R (juni 2000). "Nuclear localization and cell cycle-specific expression of CtIP, a protein that associates with the BRCA1 tumor suppressor". J. Biol. Chem. 275 (24): 18541–9. doi:10.1074/jbc.M909494199. PMID 10764811.
  185. ^ a b c Fan S, Yuan R, Ma YX, Xiong J, Meng Q, Erdos M, Zhao JN, Goldberg ID, Pestell RG, Rosen EM (august 2001). "Disruption of BRCA1 LXCXE motif alters BRCA1 functional activity and regulation of RB family but not RB protein binding". Oncogene. 20 (35): 4827–41. doi:10.1038/sj.onc.1204666. PMID 11521194.
  186. ^ Aprelikova ON, Fang BS, Meissner EG, Cotter S, Campbell M, Kuthiala A, Bessho M, Jensen RA, Liu ET (oktobar 1999). "BRCA1-associated growth arrest is RB-dependent". Proc. Natl. Acad. Sci. U.S.A. 96 (21): 11866–71. Bibcode:1999PNAS...9611866A. doi:10.1073/pnas.96.21.11866. PMC 18378. PMID 10518542.
  187. ^ a b Bochar DA, Wang L, Beniya H, Kinev A, Xue Y, Lane WS, Wang W, Kashanchi F, Shiekhattar R (juli 2000). "BRCA1 is associated with a human SWI/SNF-related complex: linking chromatin remodeling to breast cancer". Cell. 102 (2): 257–65. doi:10.1016/S0092-8674(00)00030-1. PMID 10943845.
  188. ^ Hill DA, de la Serna IL, Veal TM, Imbalzano AN (april 2004). "BRCA1 interacts with dominant negative SWI/SNF enzymes without affecting homologous recombination or radiation-induced gene activation of p21 or Mdm2". J. Cell. Biochem. 91 (5): 987–98. doi:10.1002/jcb.20003. PMID 15034933. S2CID 40668596.
  189. ^ Ouchi T, Lee SW, Ouchi M, Aaronson SA, Horvath CM (maj 2000). "Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes". Proc. Natl. Acad. Sci. U.S.A. 97 (10): 5208–13. Bibcode:2000PNAS...97.5208O. doi:10.1073/pnas.080469697. PMC 25807. PMID 10792030.
  190. ^ Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M, Ohta T, Klevit R (maj 2003). "Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex". Proc. Natl. Acad. Sci. U.S.A. 100 (10): 5646–51. Bibcode:2003PNAS..100.5646B. doi:10.1073/pnas.0836054100. PMC 156255. PMID 12732733.
  191. ^ Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit RE, Fukuda M, Ohta T (februar 2004). "Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (6): 3916–24. doi:10.1074/jbc.M308540200. PMID 14638690.
  192. ^ Kentsis A, Gordon RE, Borden KL (novembar 2002). "Control of biochemical reactions through supramolecular RING domain self-assembly". Proc. Natl. Acad. Sci. U.S.A. 99 (24): 15404–9. Bibcode:2002PNAS...9915404K. doi:10.1073/pnas.202608799. PMC 137729. PMID 12438698.
  193. ^ Wu-Baer F, Lagrazon K, Yuan W, Baer R (septembar 2003). "The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin". J. Biol. Chem. 278 (37): 34743–6. doi:10.1074/jbc.C300249200. PMID 12890688.
  194. ^ Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T (maj 2001). "The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation". J. Biol. Chem. 276 (18): 14537–40. doi:10.1074/jbc.C000881200. PMID 11278247.
  195. ^ Cable PL, Wilson CA, Calzone FJ, Rauscher FJ, Scully R, Livingston DM, Li L, Blackwell CB, Futreal PA, Afshari CA (oktobar 2003). "Novel consensus DNA-binding sequence for BRCA1 protein complexes". Mol. Carcinog. 38 (2): 85–96. doi:10.1002/mc.10148. PMID 14502648. S2CID 24956554.
  196. ^ Zhang H, Wang Q, Kajino K, Greene MI (maj 2000). "VCP, a weak ATPase involved in multiple cellular events, interacts physically with BRCA1 in the nucleus of living cells". DNA Cell Biol. 19 (5): 253–63. doi:10.1089/10445490050021168. PMID 10855792.
  197. ^ Ganesan S, Silver DP, Drapkin R, Greenberg R, Feunteun J, Livingston DM (januar 2004). "Association of BRCA1 with the inactive X chromosome and XIST RNA". Philos. Trans. R. Soc. Lond. B Biol. Sci. 359 (1441): 123–8. doi:10.1098/rstb.2003.1371. PMC 1693294. PMID 15065664.
  198. ^ Ganesan S, Silver DP, Greenberg RA, Avni D, Drapkin R, Miron A, Mok SC, Randrianarison V, Brodie S, Salstrom J, Rasmussen TP, Klimke A, Marrese C, Marahrens Y, Deng CX, Feunteun J, Livingston DM (novembar 2002). "BRCA1 supports XIST RNA concentration on the inactive X chromosome". Cell. 111 (3): 393–405. doi:10.1016/S0092-8674(02)01052-8. PMID 12419249.
  199. ^ Zheng L, Pan H, Li S, Flesken-Nikitin A, Chen PL, Boyer TG, Lee WH (oktobar 2000). "Sequence-specific transcriptional corepressor function for BRCA1 through a novel zinc finger protein, ZBRK1". Mol. Cell. 6 (4): 757–68. doi:10.1016/S1097-2765(00)00075-7. PMID 11090615.

Vanjski linkovi

[uredi | uredi izvor]
Commons logo
Commons logo
Commons ima datoteke na temu: BRCA1

Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=BRCA1&oldid=3625745"