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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Nat+Commun 2016 ; 7 (ä): ä Nephropedia Template TP
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Dynamic DNA binding licenses a repair factor to bypass roadblocks in search of DNA lesions #MMPMID26837705
Brown MW; Kim Y; Williams GM; Huck JD; Surtees JA; Finkelstein IJ
Nat Commun 2016[]; 7 (ä): ä PMID26837705show ga
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.