Exploiting the distinctive properties of the bacterial and human MutS homolog sliding clamps on mismatched DNA.

ABSTRACT: MutS homologs (MSHs) are highly conserved core components of DNA mismatch repair. Mismatch recognition provokes ATP-binding by MSH proteins that drives a conformational transition from a short-lived lesion-searching clamp to an extremely stable sliding clamp on the DNA. Here, we have expanded on previous bulk biochemical studies to examine the stability, lifetime, and kinetics of bacterial and human MSH sliding clamps on mismatched DNA using surface plasmon resonance and single-molecule analysis of fluorescently labeled proteins. We found that ATP-bound MSH complexes bound to blocked-end or very long mismatched DNAs were extremely stable over a range of ionic conditions. These observations underpinned the development of a high-throughput Förster resonance energy transfer system that specif

SUBMITTER: Britton BM 

PROVIDER: S-EPMC9597889 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature