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When two is not enough: a CtIP tetramer is required for DNA repair by Homologous Recombination

机译:当两个条件还不够时:通过同源重组修复DNA需要使用CtIP四聚体

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Homologous recombination (HR) is central to the repair of double-strand DNA breaks that occur in S/G2 phases of the cell cycle. HR relies on the CtIP protein (Ctp1 in fission yeast, Sae2 in budding yeast) for resection of DNA ends, a key step in generating the 3′-DNA overhangs that are required for the HR strand-exchange reaction. Although much has been learned about the biological importance of CtIP in DNA repair, our mechanistic insight into its molecular functions remains incomplete. It has been recently discovered that CtIP and Ctp1 share a conserved tetrameric architecture that is mediated by their N-terminal domains and is critical for their function in HR. The specific arrangement of protein chains in the CtIP/Ctp1 tetramer indicates that an ability to bridge DNA ends might be an important feature of CtIP/Ctp1 function, establishing an intriguing similarity with the known ability of the MRE11-RAD50-NBS1 complex to link DNA ends. Although the exact mechanism of action remains to be elucidated, the remarkable evolutionary conservation of CtIP/Ctp1 tetramerisation clearly points to its crucial role in HR.
机译:同源重组(HR)是修复细胞周期S / G2期中发生的双链DNA断裂的关键。 HR依靠CtIP蛋白(裂变酵母中的Ctp1,发芽酵母中的Sae2)切除DNA末端,这是产生HR链交换反应所需的3'-DNA突出端的关键步骤。尽管已经了解到很多有关CtIP在DNA修复中的生物学重要性的知识,但是我们对CtIP分子功能的机理研究仍然不完整。最近发现,CtIP和Ctp1共享保守的四聚体结构,该结构由其N端结构域介导,并且对它们在HR中的功能至关重要。 CtIP / Ctp1四聚体中蛋白质链的特定排列表明,桥接DNA末端的能力可能是CtIP / Ctp1功能的重要特征,与已知的MRE11-RAD50-NBS1复合物连接DNA的能力建立了令人着迷的相似性。结束。尽管确切的作用机理尚待阐明,但CtIP / Ctp1四聚体的显着进化保守性清楚地表明了其在HR中的关键作用。

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