起始點識別複合物

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英語ORC1ORC2英語ORC2LORC3英語ORC3LORC4英語ORC4LORC5英語ORC5LORC6英語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語pre-replication complex(pre-replication complex, pre-RC)得以組裝。複製前複合物的組分包括Cdc6英語Cdc6、Tah11(亦稱Cdt1英語Cdt1),以及MCM2英語MCM2-MCM7英語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複製許可英語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英語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]

起始點識別複合物(ORC)亞基2
鑑定
標誌ORC2
PfamPF04084舊版
InterPro英語InterProIPR007220
起始點識別複合物亞基(ORC)亞基3N-端
鑑定
標誌ORC3_N
PfamPF07034舊版
InterPro英語InterProIPR010748
起始點識別複合物亞基(ORC)亞基6
鑑定
標誌ORC6
PfamPF05460舊版
InterPro英語InterProIPR008721
CDC6在DNA複製起始中可能發揮的作用[1]

酵母細胞中,起始點識別複合物亦參與交配型英語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

編輯
  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. ^ 醫學主題詞表(MeSH)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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  6. ^ 6.0 6.1 6.2 Matsuda K, Makise M, Sueyasu Y, Takehara M, Asano T, Mizushima T. Yeast two-hybrid analysis of the origin recognition complex of Saccharomyces cerevisiae: interaction between subunits and identification of binding proteins. FEMS Yeast Res. December 2007, 7 (8): 1263–9. PMID 17825065. doi:10.1111/j.1567-1364.2007.00298.x. 
  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. 
  12. ^ 12.0 12.1 Speck C, Chen Z, Li H, Stillman B. ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Nat. Struct. Mol. Biol. November 2005, 12 (11): 965–71. PMC 2952294 . PMID 16228006. doi:10.1038/nsmb1002. 
  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. 
  14. ^ Bell SP, Dutta A. DNA replication in eukaryotic cells. Annu. Rev. Biochem. 2002, 71: 333–74. PMID 12045100. doi:10.1146/annurev.biochem.71.110601.135425. 
  15. ^ Stillman B. Origin recognition and the chromosome cycle. FEBS Lett. February 2005, 579 (4): 877–84. PMID 15680967. doi:10.1016/j.febslet.2004.12.011. 
  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. 
  17. ^ Nguyen VQ, Co C, Li JJ. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature. June 2001, 411 (6841): 1068–73. PMID 11429609. doi:10.1038/35082600. 
  18. ^ Archambault V, Ikui AE, Drapkin BJ, Cross FR. Disruption of mechanisms that prevent rereplication triggers a DNA damage response. Mol. Cell. Biol. August 2005, 25 (15): 6707–21. PMC 1190345 . PMID 16024805. doi:10.1128/MCB.25.15.6707-6721.2005. 
  19. ^ Triolo T, Sternglanz R. Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing. Nature. May 1996, 381 (6579): 251–3. PMID 8622770. doi:10.1038/381251a0. 
  20. ^ Fox CA, Ehrenhofer-Murray AE, Loo S, Rine J. The origin recognition complex, SIR1, and the S phase requirement for silencing. Science. June 1997, 276 (5318): 1547–51. PMID 9171055. doi:10.1126/science.276.5318.1547. 
  21. ^ Klemm RD, Austin RJ, Bell SP. Coordinate binding of ATP and origin DNA regulates the ATPase activity of the origin recognition complex. Cell. February 1997, 88 (4): 493–502. PMID 9038340. doi:10.1016/S0092-8674(00)81889-9. 
  22. ^ Klemm RD, Bell SP. ATP bound to the origin recognition complex is important for preRC formation. Proc. Natl. Acad. Sci. U.S.A. July 2001, 98 (15): 8361–7. PMC 37444 . PMID 11459976. doi:10.1073/pnas.131006898. 
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拓展閱讀

編輯

此條目包含有源於Pfam以及InterPro的屬於公有領域的文本 IPR007220

此條目包含有源於Pfam以及InterPro的屬於公有領域的文本 IPR010748

此條目包含有源於Pfam以及InterPro的屬於公有領域的文本 IPR008721