Ku80

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Ku80 — белок, закодированный у человека геном XRCC5.^[1] Вместе с белком Ku70 белок Ku80 образует гетеродимер, связывающийся с концами двунитевых разрывов в ДНК, и требуется для репарации ДНК путем негомологичного соединения концов (NHEJ). Также белок Ku требуется для V(D)J рекомбинации, которая использует путь NHEJ для создания разнообразия антиген-связывающих центров антител в иммунной системе млекопитающих.

Также Ku требуется для поддержания длины теломер и сайленсинга прителомерных генов.^[2]

Ku был впервые обнаружен у пациентов с системной красной волчанкой, у которых были выявлены высокие титры антител против этого белка.^[1]

Ku80 имеет несколько других названий:

• Ku аутоантиген, белок p80 волчанки
• субъединица 2 АТР-зависимой ДНК-хеликазы 2
• XRCC5 (англ. X-ray repair cross-complementing 5)

Клиническое значение

Редкий микросателлитный полиморфизм данного гена связан с опухолями у пациентов с различной чувствительностью к радиоактивности.^[3]

Взаимодействия

Показаны белок-белковые взаимодействия Ku80 с NCOA6,^[4][5] GCN5L2,^[6] Ku70,^{[6][7][8][9][10]} АТР-зависимой хеликазой синдрома Вернера,^[11][12] Тирозин-киназой 2,^[13] белком c-Abl в гомологичном киназе каталитическом участке ДНК-зависимой протеинкиназы,^[14][15][7] TERF2IP,^[16] обратной транскриптазой теломер,^[17] POU2F1^[18][15] и белком PCNA.^[15][19][20]

Примечания

1. ↑ ^{1 2} Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa).
2. ↑ Boulton SJ, Jackson SP (March 1998). «Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing». EMBO J. 17 (6): 1819–28. DOI:10.1093/emboj/17.6.1819. PMID 9501103.
3. ↑ Entrez Gene: XRCC5 X-ray repair complementing defective repair in Chinese hamster cells 5 (double-strand-break rejoining; Ku autoantigen, 80kDa).
4. ↑ Ko, L; Cardona G R, Chin W W (May. 2000). «Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator». Proc. Natl. Acad. Sci. U.S.A. 97 (11): 6212–7. ISSN 0027-8424. PMID 10823961.
5. ↑ Ko, Lan; Chin William W (Mar. 2003). «Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase». J. Biol. Chem. 278 (13): 11471–9. DOI:10.1074/jbc.M209723200. ISSN 0021-9258. PMID 12519782.
6. ↑ ^{1 2} Barlev, N A; Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman J L, Berger S L (Mar. 1998). «Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex». Mol. Cell. Biol. 18 (3): 1349–58. ISSN 0270-7306. PMID 9488450.
7. ↑ ^{1 2} Gell, D; Jackson S P (Sep. 1999). «Mapping of protein-protein interactions within the DNA-dependent protein kinase complex». Nucleic Acids Res. 27 (17): 3494–502. PMID 10446239.
8. ↑ Yang, C R; Yeh S, Leskov K, Odegaard E, Hsu H L, Chang C, Kinsella T J, Chen D J, Boothman D A (May. 1999). «Isolation of Ku70-binding proteins (KUBs)». Nucleic Acids Res. 27 (10): 2165–74. ISSN 0305-1048. PMID 10219089.
9. ↑ Singleton, B K; Torres-Arzayus M I, Rottinghaus S T, Taccioli G E, Jeggo P A (May. 1999). «The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit». Mol. Cell. Biol. 19 (5): 3267–77. ISSN 0270-7306. PMID 10207052.
10. ↑ Song, K; Jung D, Jung Y, Lee S G, Lee I (Sep. 2000). «Interaction of human Ku70 with TRF2». FEBS Lett. 481 (1): 81–5. ISSN 0014-5793. PMID 10984620.
11. ↑ Karmakar, Parimal; Snowden Carey M, Ramsden Dale A, Bohr Vilhelm A (Aug. 2002). «Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus». Nucleic Acids Res. 30 (16): 3583–91. PMID 12177300.
12. ↑ Li, B; Comai L (Sep. 2000). «Functional interaction between Ku and the werner syndrome protein in DNA end processing». J. Biol. Chem. 275 (37): 28349–52. DOI:10.1074/jbc.C000289200. ISSN 0021-9258. PMID 10880505.
13. ↑ Adam, L; Bandyopadhyay D, Kumar R (Jan. 2000). «Interferon-alpha signaling promotes nucleus-to-cytoplasmic redistribution of p95Vav, and formation of a multisubunit complex involving Vav, Ku80, and Tyk2». Biochem. Biophys. Res. Commun. 267 (3): 692–6. DOI:10.1006/bbrc.1999.1978. ISSN 0006-291X. PMID 10673353.
14. ↑ Jin, S; Kharbanda S, Mayer B, Kufe D, Weaver D T (Oct. 1997). «Binding of Ku and c-Abl at the kinase homology region of DNA-dependent protein kinase catalytic subunit». J. Biol. Chem. 272 (40): 24763–6. ISSN 0021-9258. PMID 9312071.
15. ↑ ^{1 2 3} Matheos, Diamanto; Ruiz Marcia T, Price Gerald B, Zannis-Hadjopoulos Maria (Oct. 2002). «Ku antigen, an origin-specific binding protein that associates with replication proteins, is required for mammalian DNA replication». Biochim. Biophys. Acta 1578 (1-3): 59–72. ISSN 0006-3002. PMID 12393188.
16. ↑ O'Connor, Matthew S; Safari Amin, Liu Dan, Qin Jun, Songyang Zhou (Jul. 2004). «The human Rap1 protein complex and modulation of telomere length». J. Biol. Chem. 279 (27): 28585–91. DOI:10.1074/jbc.M312913200. ISSN 0021-9258. PMID 15100233.
17. ↑ Chai, Weihang; Ford Lance P, Lenertz Lisa, Wright Woodring E, Shay Jerry W (Dec. 2002). «Human Ku70/80 associates physically with telomerase through interaction with hTERT». J. Biol. Chem. 277 (49): 47242–7. DOI:10.1074/jbc.M208542200. ISSN 0021-9258. PMID 12377759.
18. ↑ Schild-Poulter, C; Pope L, Giffin W, Kochan J C, Ngsee J K, Traykova-Andonova M, Haché R J (May. 2001). «The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase». J. Biol. Chem. 276 (20): 16848–56. DOI:10.1074/jbc.M100768200. ISSN 0021-9258. PMID 11279128.
19. ↑ Ohta, Satoshi; Shiomi Yasushi, Sugimoto Katsunori, Obuse Chikashi, Tsurimoto Toshiki (Oct. 2002). «A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein». J. Biol. Chem. 277 (43): 40362–7. DOI:10.1074/jbc.M206194200. ISSN 0021-9258. PMID 12171929.
20. ↑ Balajee, A S; Geard C R (Mar. 2001). «Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells». Nucleic Acids Res. 29 (6): 1341–51. PMID 11239001.

Литература

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