Molecular basis of the dual role of the Mlh1-Mlh3 endonuclease in MMR and in meiotic crossover formation
During meiosis, programmed chromosome breakage and subsequent double-stranded DNA (dsDNA) break repair help ensure correct chromosome segregation and promote genetic diversity of the progeny. In budding yeast, which utilizes meiotic recombination pathways conserved in mice and humans, the majority of meiotic crossovers are initiated through the formation of a DNA Holliday junction, which requires the endonuclease activity of the Mlh1-Mlh3 DNA mismatch repair factor to be resolved exclusively into a crossover product. Here, we combined structural biology, biochemical, and genetic analyses to compare the Mlh1-Mlh3 structure and functions with the main mismatch repair endonuclease Mlh1-Pms1. We characterize structural differences around their respective endonuclease sites. We also characterize mutants associated with condensation and filament formation of the Mlh1-Mlh3 heterodimer.