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标签:DNA 端部 修复
摘要 : 断开的DNA端部必须被保持在一起,才能使DNA得到修复

 断开的DNA端部必须被保持在一起,才能使DNA得到修复。然而,这一过程的细节目前尚不清楚。Ineke Brouwer等人结合了不同单分子技术,对 XRCC4 和 XLF修复蛋白在DNA端部的相互作用工具进行了研究。他们发现,这些蛋白形成了袖状的活动异聚复合体,它们沿DNA迅速滑动,将DNA两端连接起来,将断开的碎片保持在一起,以帮助它们重新结合。


Sliding sleeves of XRCC4–XLF bridge DNA and connect fragments of broken DNA


Non-homologous end joining (NHEJ) is the primary pathway for repairing DNA double-strand breaks (DSBs) in mammalian cells1. Such breaks are formed, for example, during gene-segment rearrangements in the adaptive immune system or by cancer therapeutic agents. Although the core components of the NHEJ machinery are known, it has remained difficult to assess the specific roles of these components and the dynamics of bringing and holding the fragments of broken DNA together. The structurally similar XRCC4 and XLF proteins are proposed to assemble as highly dynamic filaments at (or near) DSBs2. Here we show, using dual- and quadruple-trap optical tweezers combined with fluorescence microscopy, how human XRCC4, XLF and XRCC4–XLF complexes interact with DNA in real time. We find that XLF stimulates the binding of XRCC4 to DNA, forming heteromeric complexes that diffuse swiftly along the DNA. Moreover, we find that XRCC4–XLF complexes robustly bridge two independent DNA molecules and that these bridges are able to slide along the DNA. These observations suggest that XRCC4–XLF complexes form mobile sleeve-like structures around DNA that can reconnect the broken ends very rapidly and hold them together. Understanding the dynamics and regulation of this mechanism will lead to clarification of how NHEJ proteins are involved in generating chromosomal translocations3, 4.

来源: Nature 浏览次数:1


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