The Mlh1-Pms1 endonuclease uses ATP to preserve DNA discontinuities as strand discrimination signals to facilitate mismatch repair.

ABSTRACT: In eukaryotic post-replicative mismatch repair, MutS homologs (MSH) detect mismatches and recruit MLH complexes to nick the newly replicated DNA strand upon activation by the replication processivity clamp, PCNA. This incision enables mismatch removal and DNA repair. Biasing MLH endonuclease activity to the newly replicated DNA strand is crucial for repair. In reconstituted in vitro assays, PCNA is loaded at pre-existing discontinuities and orients the major MLH endonuclease Mlh1-Pms1/MLH1-PMS2 (yeast/human) to nick the discontinuous strand. In vivo, newly replicated DNA transiently contains discontinuities which are critical for efficient mismatch repair. How these discontinuities are preserved as strand discrimination signals during the window of time where mismatch repair

SUBMITTER: Piscitelli JM 

PROVIDER: S-EPMC11195183 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature