WRN (gen)

Vernerov sindrom, RecQ helikaza
Vernerov sindrom, RecQ helikaza
	Struktura DNA- i protein- vezujućeg motiva Vernerovog proteina. PDB prikaz baziran na 2axl.
Dostupne strukture
	2AXL, 2DGZ, 2E1E, 2E1F, 2FBT, 2FBV, 2FBX, 2FBY, 2FC0, 3AAF
Identifikatori
Simboli	WRN; RECQ3; RECQL2; RECQL3
Vanjski ID	OMIM: 604611 MGI: 109635 HomoloGene: 6659 GeneCards: WRN Gene
EC broj	3.6.4.12
Ontologija gena
Molekularna funkcija	• nukleotidno vezivanje; • vezivanje jona magnezijuma; • Y-forma DNK vezivanja; • DNK vezivanje; • Aktivnost DNK helikaze; • Aktivnost ATP-zavisne DNK helikaze; • Aktivnost helikaze;
Celularna komponenta	• intracelularan; • nukleus; • nukleoplazma; • nukleolus; • centrozom; • MutLalpha kompleks;
Biološki proces	• održavanje telomera; • DNK sinteza tokom popravke DNK; • replikativno ćelijsko starenje; • metabolički proces nukleobaza; • ATP katabolički proces; • DNA metabolički proces; • replikacija DNK; • popravka isecanjem baza; • rekombinacija DNK; • respons na stimulus DNK oštećenja; • respons na oksidativni stres;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	7486
Ensembl	ENSG00000165392
UniProt	Q14191
RefSeq (mRNA)	NM_000553.4
RefSeq (protein)	NP_000544.2
Lokacija (UCSC)	Chr 8:; 30.89 - 31.03 Mb
PubMed pretraga	[1]

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.

Interakcije[уреди | уреди извор]

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]

Reference[уреди | уреди извор]

^ ^а ^б Karmakar, Parimal; Snowden Carey M; et al. (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. PMC 134248 . PMID 12177300. doi:10.1093/nar/gkf482.
^ ^а ^б Li, B; Comai L (2000). „Functional interaction between Ku and the werner syndrome protein in DNA end processing”. J. Biol. Chem. UNITED STATES. 275 (37): 28349—52. ISSN 0021-9258. PMID 10880505. doi:10.1074/jbc.C000289200.
^ Rodríguez-López, Ana M; Jackson Dean A; et al. (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. ISSN 0047-6374. PMID 12633936. doi:10.1016/S0047-6374(02)00131-8.
^ Huang, S; Beresten S; et al. (2000). „Characterization of the human and mouse WRN 3'-->5' exonuclease”. Nucleic Acids Res. ENGLAND. 28 (12): 2396—405. PMC 102739 . PMID 10871373. doi:10.1093/nar/28.12.2396.
^ Kim, S T; Lim D S; et al. (1999). „Substrate specificities and identification of putative substrates of ATM kinase family members”. J. Biol. Chem. UNITED STATES. 274 (53): 37538—43. ISSN 0021-9258. PMID 10608806. doi:10.1074/jbc.274.53.37538.
^ Karmakar, Parimal; Piotrowski Jason; et al. (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. ISSN 0021-9258. PMID 11889123. doi:10.1074/jbc.M111523200.
^ Yang, Qin; Zhang Ran; et al. (2002). „The processing of Holliday junctions by BLM and WRN helicases is regulated by p53”. J. Biol. Chem. United States. 277 (35): 31980—7. ISSN 0021-9258. PMID 12080066. doi:10.1074/jbc.M204111200.
^ Brosh, R M; Karmakar P; et al. (2001). „p53 Modulates the exonuclease activity of Werner syndrome protein”. J. Biol. Chem. United States. 276 (37): 35093—102. ISSN 0021-9258. PMID 11427532. doi:10.1074/jbc.M103332200.
^ Sharma, Sudha; Sommers Joshua A; et al. (2004). „Stimulation of flap endonuclease-1 by the Bloom's syndrome protein”. J. Biol. Chem. United States. 279 (11): 9847—56. ISSN 0021-9258. PMID 14688284. doi:10.1074/jbc.M309898200.
^ Brosh, R M; von Kobbe C; et al. (2001). „Werner syndrome protein interacts with human flap endonuclease 1 and stimulates its cleavage activity”. EMBO J. England. 20 (20): 5791—801. ISSN 0261-4189. PMC 125684 . PMID 11598021. doi:10.1093/emboj/20.20.5791.
^ Kawabe Yi, Yi; Branzei D; et al. (2001). „A novel protein interacts with the Werner's syndrome gene product physically and functionally”. J. Biol. Chem. United States. 276 (23): 20364—9. ISSN 0021-9258. PMID 11301316. doi:10.1074/jbc.C100035200.
^ von Kobbe, Cayetano; Karmakar Parimal; et al. (2002). „Colocalization, physical, and functional interaction between Werner and Bloom syndrome proteins”. J. Biol. Chem. United States. 277 (24): 22035—44. ISSN 0021-9258. PMID 11919194. doi:10.1074/jbc.M200914200.
^ Opresko, Patricia L; von Kobbe Cayetano; et al. (2002). „Telomere-binding protein TRF2 binds to and stimulates the Werner and Bloom syndrome helicases”. J. Biol. Chem. United States. 277 (43): 41110—9. ISSN 0021-9258. PMID 12181313. doi:10.1074/jbc.M205396200.

Literatura[уреди | уреди извор]

Comai L, Li B (2004). „The Werner syndrome protein at the crossroads of DNA repair and apoptosis”. Mech Ageing Dev. 125 (8): 521—8. PMID 15336909. doi:10.1016/j.mad.2004.06.004.
Lee JW, Harrigan J, Opresko PL, Bohr VA (2005). „Pathways and functions of the Werner syndrome protein”. Mech Ageing Dev. 126 (1): 79—86. PMID 15610765. doi:10.1016/j.mad.2004.09.011.
Monnat RJ Jr; Saintigny Y (2004). „Werner syndrome protein--unwinding function to explain disease”. Sci Aging Knowledge Environ. 2004 (13): re3. PMID 15056797. doi:10.1126/sageke.2004.13.re3.
Ozgenc A, Loeb LA (2005). „Current advances in unraveling the function of the Werner syndrome protein”. Mutat Res. 577 (1–2): 237—51. PMID 15946710. doi:10.1016/j.mrfmmm.2005.03.020.
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. PMID 15084309. doi:10.1016/j.dnarep.2004.01.002.
Moser MJ, Oshima J, Monnat RJ (1999). „WRN mutations in Werner syndrome”. Hum. Mutat. 13 (4): 271—9. PMID 10220139. doi:10.1002/(SICI)1098-1004(1999)13:4<271::AID-HUMU2>3.0.CO;2-Q.
Kastan MB, Lim DS (2001). „The many substrates and functions of ATM”. Nat. Rev. Mol. Cell Biol. 1 (3): 179—86. PMID 11252893. doi:10.1038/35043058.