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首页> 外文期刊>Cell cycle >Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80.
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Recruitment of proteins to DNA double-strand breaks: MDC1 directly recruits RAP80.

机译:蛋白质招募至DNA双链断裂:MDC1直接招募RAP80。

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摘要

DNA double-strand breaks (DSBs) are the most severe type of DNA damage. Occurrence of DSBs in the cell activates the DNA damage response (DDR), which involves signaling cascades that sense and respond to the damage. Promptly after DSB induction, DDR proteins accumulate surrounding both DNA ends and form microscopically-visible foci. Recently, we demonstrated that the key DDR protein MDC1 directly binds RAP80, an additional DDR protein that recruits BRCA1 to DSBs. We provided evidences that the MDC1-RAP80 interaction depends on a ubiquitylation event on K-1977 of MDC1. However, it remained unknown whether K-1977 of MDC1 is required for the recruitment of RAP80 to DSBs. Here we show that K-1977 of MDC1 is necessary for focus formation by RAP80. Nevertheless, it has not effect on focus formation by gamma-H2AX, MDC1 or 53BP1. The results imply a role for the MDC1-RAP80 interaction in focus formation by the RAP80-BRCA1 complex. In light of these recent results we discuss several aspects of the complexity of focus formation and present a model for the involvement of individual and complex recruitment mechanisms in focus formation.
机译:DNA双链断裂(DSB)是最严重的DNA损伤类型。细胞中DSB的存在会激活DNA损伤反应(DDR),后者涉及感知和响应损伤的信号级联反应。在DSB诱导后,DDR蛋白立即在DNA的两个末端聚集并形成显微镜下可见的焦点。最近,我们证明了关键的DDR蛋白MDC1直接结合RAP80,RAP80是将BRCA1募集到DSB的另一种DDR蛋白。我们提供了证据,表明MDC1-RAP80相互作用取决于MDC1的K-1977上的泛素化事件。但是,将RAP80招募到DSB是否需要MDC1的K-1977是未知的。在这里我们显示MDC1的K-1977对于RAP80形成焦点是必需的。但是,它不会影响由γ-H2AX,MDC1或53BP1形成的焦点。结果暗示了MDC1-RAP80相互作用在RAP80-BRCA1复合体形成焦点中的作用。根据这些最新结果,我们讨论了焦点形成复杂性的几个方面,并提出了一个模型,用于将单个和复杂的招聘机制纳入焦点形成。

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