The mismatch repair factor Mlh1-Pms1 uses ATP to compact and remodel DNA.

In eukaryotes, mismatch repair begins with MutS homolog (MSH) complexes, which scan newly replicated DNA for mismatches. Upon mismatch detection, MSH complexes recruit the PCNA-stimulated endonuclease Mlh1-Pms1/PMS2 (yeast/human), which nicks the DNA to allow downstream proteins to remove the mismatch. Past work has shown that although Mlh1-Pms1 is an ATPase and this activity is important in vivo, ATP is not required to nick DNA. Our data, using yeast as a model, suggests that Mlh1-Pms1 forms oligomeric complexes that drive DNA conformational rearrangements using the protein's ATPase activity. Experiments with non-B-form DNA structures, common in microsatellite regions, show that these structures inhibit Mlh1-Pms1's activities, likely through impeding Mlh1-Pms1-dependent DNA conformational changes. This could explain an additional mode for instability in these regions of the genome. These findings highlight the importance of DNA compaction and topological rearrangements in Mlh1-Pms1's function and provide insight into how mismatch repair relies on DNA structure to coordinate events.