Peer-Reviewed Journal Details
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Brown, MW;Kim, Y;Williams, GM;Huck, JD;Surtees, JA;Finkelstein, IJ
2016
February
Nature Communications
Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions
Published
Altmetric: 12WOS: 6 ()
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SACCHAROMYCES-CEREVISIAE MSH2-MSH3 MISMATCH REPAIR SINGLE-MOLECULE RECOGNITION COMPLEX SLIDING CLAMP PROTEIN MUTS ATP RECOMBINATION DIFFUSION HMSH2-HMSH6
7
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.
2041-1723
10.1038/ncomms10607
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