Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions.
Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions.
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DOI：
10.1038/ncomms10607
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发表时间：
2016-02-03
影响因子：
16.6
通讯作者：
Finkelstein IJ
中科院分区：
文献类型：
--
作者：
Brown MW;Kim Y;Williams GM;Huck JD;Surtees JA;Finkelstein IJ
DNA-binding proteins search for specific targets via facilitated diffusion along a crowded genome. However, little is known about how crowded DNA modulates facilitated diffusion and target recognition. Here we use DNA curtains and single-molecule fluorescence imaging to investigate how Msh2–Msh3, a eukaryotic mismatch repair complex, navigates on crowded DNA. Msh2–Msh3 hops over nucleosomes and other protein roadblocks, but maintains sufficient contact with DNA to recognize a single lesion. In contrast, Msh2–Msh6 slides without hopping and is largely blocked by protein roadblocks. Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a chimeric Msh2–Msh6(3MBD) to bypass nucleosomes. Our studies contrast how Msh2–Msh3 and Msh2–Msh6 navigate on a crowded genome and suggest how Msh2–Msh3 locates DNA lesions outside of replication-coupled repair. These results also provide insights into how DNA repair factors search for DNA lesions in the context of chromatin. DNA-binding proteins need to scan the genome to find their targets though how this occurs in the crowded nuclear environment is poorly understood. Here the authors use single-molecular fluorescence to show the repair complex Msh2-Msh3 can hop over blocks that impede the sliding complex Msh2-Msh6.
