2020 journal article

Recurrent mismatch binding by MutS mobile clamps on DNA localizes repair complexes nearby

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 117(30), 17775–17784.

By: P. Hao n, S. LeBlanc n, B. Case *, T. Elston *, M. Hingorani *, D. Erie *, K. Weninger n 

author keywords: smFRET; MMR; mismatch repair; MutS
MeSH headings : Adenosine Triphosphatases / metabolism; Adenosine Triphosphate / metabolism; Base Pair Mismatch; DNA / chemistry; DNA / genetics; DNA / metabolism; DNA Mismatch Repair; Hydrolysis; Models, Molecular; Multiprotein Complexes / metabolism; MutL Proteins / chemistry; MutL Proteins / metabolism; MutS DNA Mismatch-Binding Protein / chemistry; MutS DNA Mismatch-Binding Protein / metabolism; Structure-Activity Relationship
TL;DR: It is revealed that after the initial mobile clamp formation event, MutS undergoes frequent cycles of mismatch rebinding and mobile clamp reformation without releasing DNA, and mechanisms that localize repair complexes to the vicinity of the mismatch are supported. (via Semantic Scholar)
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Added: August 17, 2020

Significance DNA mismatch repair (MMR) proteins are essential for correcting base incorporation errors that occur during replication, greatly enhancing genomic stability. In all organisms, MutS and MutL homologs initiate MMR repair and are involved in several other DNA transactions, including DNA-damage–induced apoptosis and homologous recombination. Our study reveals that MutS mobile clamps hydrolyze ATP while remaining bound to DNA and frequently revisit the mismatch. We also find that MutL converts MutS mobile clamps into immobile MutS–MutL complexes. These immobile, multimeric complexes present a striking contrast to current MMR initiation models that envision MutS–MutL sliding freely on the DNA, effectively diffusing away from the mismatch. Our results support mechanisms that localize repair complexes to the vicinity of the mismatch.