WRN (gen)
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WRN (Vernerov sindrom) je ljudski gen koji korira Vernerov protein. On je helikaza. Helikaze su enzimi koji generalno odvijaju i razdvajaju lance dvolančane DNK. Te aktivnosti su neophodne pre kopiranja DNK u pripremi za ćelijsku deobu (DNK). Helikaze su takođe kritične u procesu transkripcije. Vernerov protein ima kritičnu ulogu u popravci DNK. Ovaj protein pomaže u održavanju strukture i integriteta DNK.
WRN gen se nalazi na kratkoj (p) ruci hromozoma 8 između pozicija 12 i 11.2, od baznog para 31,010,319 do baznog para 31,150,818.
ATP-zavisna helikaza Vernerovog sindroma formira interakcije sa Ku70,[1][2] PCNA,[3][4] DNA-PKcs,[5][6] P53,[7][8] Ku80,[1][2] endonukleaza 1 specifična za Flap strukturu,[9][10] WRNIP1,[11] Bloom sindrom protein[12] i TERF2.[13]
- ↑ 1,0 1,1 Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (August 2002). „Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus”. Nucleic Acids Res. (England) 30 (16): 3583–91. DOI:10.1093/nar/gkf482. PMC 134248. PMID 12177300.
- ↑ 2,0 2,1 Li, B; Comai L (September 2000). „Functional interaction between Ku and the werner syndrome protein in DNA end processing”. J. Biol. Chem. (UNITED STATES) 275 (37): 28349–52. DOI:10.1074/jbc.C000289200. ISSN 0021-9258. PMID 10880505.
- ↑ Rodríguez-López, Ana M; Jackson Dean A, Nehlin Jan O, Iborra Francisco, Warren Anna V, Cox Lynne S (February 2003). „Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA”. Mech. Ageing Dev. (Ireland) 124 (2): 167–74. DOI:10.1016/S0047-6374(02)00131-8. ISSN 0047-6374. PMID 12633936.
- ↑ Huang, S; Beresten S, Li B, Oshima J, Ellis N A, Campisi J (June 2000). „Characterization of the human and mouse WRN 3'-->5' exonuclease”. Nucleic Acids Res. (ENGLAND) 28 (12): 2396–405. DOI:10.1093/nar/28.12.2396. PMC 102739. PMID 10871373.
- ↑ Kim, S T; Lim D S, Canman C E, Kastan M B (December 1999). „Substrate specificities and identification of putative substrates of ATM kinase family members”. J. Biol. Chem. (UNITED STATES) 274 (53): 37538–43. DOI:10.1074/jbc.274.53.37538. ISSN 0021-9258. PMID 10608806.
- ↑ Karmakar, Parimal; Piotrowski Jason, Brosh Robert M, Sommers Joshua A, Miller Susan P Lees, Cheng Wen-Hsing, Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (May 2002). „Werner protein is a target of DNA-dependent protein kinase in vivo and in vitro, and its catalytic activities are regulated by phosphorylation”. J. Biol. Chem. (United States) 277 (21): 18291–302. DOI:10.1074/jbc.M111523200. ISSN 0021-9258. PMID 11889123.
- ↑ Yang, Qin; Zhang Ran, Wang Xin Wei, Spillare Elisa A, Linke Steven P, Subramanian Deepa, Griffith Jack D, Li Ji Liang, Hickson Ian D, Shen Jiang Cheng, Loeb Lawrence A, Mazur Sharlyn J, Appella Ettore, Brosh Robert M, Karmakar Parimal, Bohr Vilhelm A, Harris Curtis C (August 2002). „The processing of Holliday junctions by BLM and WRN helicases is regulated by p53”. J. Biol. Chem. (United States) 277 (35): 31980–7. DOI:10.1074/jbc.M204111200. ISSN 0021-9258. PMID 12080066.
- ↑ Brosh, R M; Karmakar P, Sommers J A, Yang Q, Wang X W, Spillare E A, Harris C C, Bohr V A (September 2001). „p53 Modulates the exonuclease activity of Werner syndrome protein”. J. Biol. Chem. (United States) 276 (37): 35093–102. DOI:10.1074/jbc.M103332200. ISSN 0021-9258. PMID 11427532.
- ↑ Sharma, Sudha; Sommers Joshua A, Wu Leonard, Bohr Vilhelm A, Hickson Ian D, Brosh Robert M (March 2004). „Stimulation of flap endonuclease-1 by the Bloom's syndrome protein”. J. Biol. Chem. (United States) 279 (11): 9847–56. DOI:10.1074/jbc.M309898200. ISSN 0021-9258. PMID 14688284.
- ↑ Brosh, R M; von Kobbe C, Sommers J A, Karmakar P, Opresko P L, Piotrowski J, Dianova I, Dianov G L, Bohr V A (October 2001). „Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity”. EMBO J. (England) 20 (20): 5791–801. DOI:10.1093/emboj/20.20.5791. ISSN 0261-4189. PMC 125684. PMID 11598021.
- ↑ Kawabe Yi; Branzei D, Hayashi T, Suzuki H, Masuko T, Onoda F, Heo S J, Ikeda H, Shimamoto A, Furuichi Y, Seki M, Enomoto T (June 2001). „A novel protein interacts with the Werner's syndrome gene product physically and functionally”. J. Biol. Chem. (United States) 276 (23): 20364–9. DOI:10.1074/jbc.C100035200. ISSN 0021-9258. PMID 11301316.
- ↑ von Kobbe, Cayetano; Karmakar Parimal, Dawut Lale, Opresko Patricia, Zeng Xianmin, Brosh Robert M, Hickson Ian D, Bohr Vilhelm A (June 2002). „Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins”. J. Biol. Chem. (United States) 277 (24): 22035–44. DOI:10.1074/jbc.M200914200. ISSN 0021-9258. PMID 11919194.
- ↑ Opresko, Patricia L; von Kobbe Cayetano, Laine Jean-Philippe, Harrigan Jeanine, Hickson Ian D, Bohr Vilhelm A (October 2002). „Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases”. J. Biol. Chem. (United States) 277 (43): 41110–9. DOI:10.1074/jbc.M205396200. ISSN 0021-9258. PMID 12181313.
- Comai L, Li B (2004). „The Werner syndrome protein at the crossroads of DNA repair and apoptosis”. Mech Ageing Dev 125 (8): 521–8. DOI:10.1016/j.mad.2004.06.004. PMID 15336909.
- Lee JW, Harrigan J, Opresko PL, Bohr VA (2005). „Pathways and functions of the Werner syndrome protein”. Mech Ageing Dev 126 (1): 79–86. DOI:10.1016/j.mad.2004.09.011. PMID 15610765.
- Monnat RJ Jr, Saintigny Y (2004). „Werner syndrome protein--unwinding function to explain disease”. Sci Aging Knowledge Environ 2004 (13): re3. DOI:10.1126/sageke.2004.13.re3. PMID 15056797.
- Ozgenc A, Loeb LA (2005). „Current advances in unraveling the function of the Werner syndrome protein”. Mutat Res 577 (1–2): 237–51. DOI:10.1016/j.mrfmmm.2005.03.020. PMID 18636710.
- Swanson C, Saintigny Y, Emond MJ, Monnat RJ Jr (2004). „The Werner syndrome protein has separable recombination and survival functions”. DNA Repair (Amst) 3 (5): 475–82. DOI:10.1016/j.dnarep.2004.01.002. PMID 15084309.
- Moser MJ, Oshima J, Monnat RJ (1999). „WRN mutations in Werner syndrome”. Hum. Mutat. 13 (4): 271–9. DOI:10.1002/(SICI)1098-1004(1999)13:4<271::AID-HUMU2>3.0.CO;2-Q. PMID 10220139.
- Kastan MB, Lim DS (2001). „The many substrates and functions of ATM”. Nat. Rev. Mol. Cell Biol. 1 (3): 179–86. DOI:10.1038/35043058. PMID 11252893.