Mlh1-Pms1 couples ATP-driven DNA compaction with nick-dependent endonuclease activation.

ABSTRACT: In eukaryotes, mismatch repair begins with MutS homolog (MSH) complexes detecting mismatches and recruiting the proliferating cell nuclear antigen (PCNA)-stimulated endonuclease Mlh1-Pms1/PMS2 (yeast/human), which nicks the DNA to allow downstream proteins to remove the mismatch. Although Mlh1-Pms1 is an ATPase and this activity is essential in vivo, ATP is not required for nicking in vitro, leaving its function unresolved. Using yeast proteins, we show that Mlh1-Pms1 uses ATP to compact continuous DNA, a behavior which may act as a search mechanism for strand-discrimination signals. When a pre-existing nick is encountered, compaction is suppressed and Mlh1-Pms1 instead stabilizes the site, protecting it from replication factor C (RFC)/PCNA-induced melting. Phased nicking assays further re

SUBMITTER: Collingwood BW 

PROVIDER: S-EPMC12673852 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature