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起始點識別複合物

维基百科,自由的百科全书
起始點識別複合物(ORC)亞基2
鑑定
標誌ORC2
PfamPF04084旧版
InterPro英语InterProIPR007220
起始點識別複合物亞基(ORC)亞基3N-端
鑑定
標誌ORC3_N
PfamPF07034旧版
InterPro英语InterProIPR010748
起始點識別複合物亞基(ORC)亞基6
鑑定
標誌ORC6
PfamPF05460旧版
InterPro英语InterProIPR008721
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

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  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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  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. 
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  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. 
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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