起始點識別複合物

在分子生物學中，起始點識別複合物（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：ORC1）、ORC2（英语：ORC2L）、ORC3（英语：ORC3L）、ORC4（英语：ORC4L）、ORC5（英语：ORC5L）、ORC6（英语：ORC6L）基因編碼。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。起始點識別複合物對DNA複製的啓動來說不可或缺。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。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。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。 在酵母細胞中，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。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。 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。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。另外，Orc1的ATP酶活性亦與複製前複合物的生成有關。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。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。 Borlado LR, Méndez J. 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PMID 16387651. doi:10.1016/j.molcel.2005.11.023.  Semple JW, Da-Silva LF, Jervis EJ, Ah-Kee J, Al-Attar H, Kummer L, Heikkila JJ, Pasero P, Duncker BP. An essential role for Orc6 in DNA replication through maintenance of pre-replicative complexes. EMBO J. November 2006, 25 (21): 5150–8. PMC 1630405 . PMID 17053779. doi:10.1038/sj.emboj.7601391.  Stephen P. Bell and Anindya Dutta, DNA REPLICATION IN EUKARYOTIC CELLS, Annual Review of Biochemistry, 2002. doi:10.1146/annurev.biochem.71.110601.135425. A comprehensive review of molecular DNA replication. 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