起始點識別複合物

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(重定向自起始識別複合體
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起始點識別複合物(ORC)亞基2
鉴定
标志 ORC2
Pfam(蛋白家族查询站) PF04084
InterPro(蛋白数据整合站) IPR007220
起始點識別複合物亞基(ORC)亞基3N-端
鉴定
标志 ORC3_N
Pfam(蛋白家族查询站) PF07034
InterPro(蛋白数据整合站) IPR010748
起始點識別複合物亞基(ORC)亞基6
鉴定
标志 ORC6
Pfam(蛋白家族查询站) PF05460
InterPro(蛋白数据整合站) IPR008721
CDC6在DNA複製起始中可能發揮的作用[1]

分子生物學中,起始點識別複合物[2](origin recognition complex, ORC)是指一種真核生物體內的含有多個亞基、與DNA結合的複合物。它與DNA通過一種ATP依賴性的方式相連,使得DNA複製得以啓動。該複合物的幾個亞基分別由ORC1英语ORC1ORC2英语ORC2LORC3英语ORC3LORC4英语ORC4LORC5英语ORC5LORC6英语ORC6L基因編碼[3][4][5]。起始點識別複合物不僅在真核生物DNA複製期間存在,在整個細胞週期的其餘時段也與複製起點結合[6]。起始點識別複合物對DNA複製的啓動來說不可或缺[7][8][9]。與複製起點結合的起始點識別複合物使得複製前複合物英语pre-replication complex(pre-replication complex, pre-RC)得以組裝。複製前複合物的組分包括Cdc6英语Cdc6、Tah11(亦稱Cdt1英语Cdt1),以及MCM2英语MCM2-MCM7英语MCM7複合物[10][11][12]。複製前複合物在G1期的組裝對於S期的DNA複製前的DNA複製許可英语licensing factor至關重要。不經過許可,DNA複製就無法進行[13][14][15]週期素依賴性蛋白激酶Cdc28英语Cdc28能磷酸化Orc2、Orc6、Cdc6,以調節DNA複製的起始(包括封鎖G2/M期的複製再啓動),進而達到調節細胞週期的目的[6][16][17][18]

酵母細胞中,起始點識別複合物亦參與交配型英语Mating of yeast相關的基因位點HML和HMR的沉默[7][8][9]。起始點識別複合物參與HML、HMR位點的染色質組裝,讓Sirl沉默蛋白裝入染色質中,使得這兩個位點沉默[9][19][20]

Orc1以及Orc5這兩個起始點識別複合物的亞基均與ATP結合,不過只有Orc1具有ATP酶活性[21]。Orc1與ATP的結合使起始點識別複合物得以與DNA結合,對細胞的生存至關重要[12]。另外,Orc1的ATP酶活性亦與複製前複合物的生成有關[22][23][24]。而Orc5與ATP的結合則使得起始點識別複合物能作爲一個整體穩定存在。只有Orc1到Orc5這5個亞基對複合物與複製起點的結合是必需的。Orc6則能使複製前複合物在合成之後能穩定存在[25]。對起始點識別複合物內部的相互作用的研究表明,Orc2、Orc3、Orc6可能組成了複合物的核心部分[6]

參考文獻[编辑]

  1. ^ Borlado LR, Méndez J. CDC6: from DNA replication to cell cycle checkpoints and oncogenesis. Carcinogenesis. February 2008, 29 (2): 237–43. PMID 18048387. doi:10.1093/carcin/bgm268. 
  2. ^ 譯名來自:朱玉賢等. 《分子生物學》 第三版. 2008: pp.49. ISBN 978-7-04-022214-2. 
  3. ^ MeSH(醫學主題詞)上面的Origin+Recognition+Complex
  4. ^ Dutta A, Bell SP. Initiation of DNA replication in eukaryotic cells. Annu. Rev. Cell Dev. Biol. 1997, 13: 293–332. PMID 9442876. doi:10.1146/annurev.cellbio.13.1.293. 
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  7. ^ 7.0 7.1 Bell SP, Stillman B. ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature. May 1992, 357 (6374): 128–34. PMID 1579162. doi:10.1038/357128a0. 
  8. ^ 8.0 8.1 Bell SP, Mitchell J, Leber J, Kobayashi R, Stillman B. The multidomain structure of Orc1p reveals similarity to regulators of DNA replication and transcriptional silencing. Cell. November 1995, 83 (4): 563–8. PMID 7585959. doi:10.1016/0092-8674(95)90096-9. 
  9. ^ 9.0 9.1 9.2 Gibson DG, Bell SP, Aparicio OM. Cell cycle execution point analysis of ORC function and characterization of the checkpoint response to ORC inactivation in Saccharomyces cerevisiae. Genes Cells. June 2006, 11 (6): 557–73. PMID 16716188. doi:10.1111/j.1365-2443.2006.00967.x. 
  10. ^ Rao H, Stillman B. The origin recognition complex interacts with a bipartite DNA binding site within yeast replicators. Proc. Natl. Acad. Sci. U.S.A. March 1995, 92 (6): 2224–8. PMC 42456. PMID 7892251. doi:10.1073/pnas.92.6.2224. 
  11. ^ Rowley A, Cocker JH, Harwood J, Diffley JF. Initiation complex assembly at budding yeast replication origins begins with the recognition of a bipartite sequence by limiting amounts of the initiator, ORC. EMBO J. June 1995, 14 (11): 2631–41. PMC 398377. PMID 7781615. 
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  13. ^ Kelly TJ, Brown GW. Regulation of chromosome replication. Annu. Rev. Biochem. 2000, 69: 829–80. PMID 10966477. doi:10.1146/annurev.biochem.69.1.829. 
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  16. ^ Weinreich M, Liang C, Chen HH, Stillman B. Binding of cyclin-dependent kinases to ORC and Cdc6p regulates the chromosome replication cycle. Proc. Natl. Acad. Sci. U.S.A. September 2001, 98 (20): 11211–7. PMC 58709. PMID 11572976. doi:10.1073/pnas.201387198. 
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拓展閱讀[编辑]

此条目包含有源于Pfam以及InterPro的属于公有领域的文本 IPR007220

此条目包含有源于Pfam以及InterPro的属于公有领域的文本 IPR010748

此条目包含有源于Pfam以及InterPro的属于公有领域的文本 IPR008721