The DNA mismatch repair proteins, MLH1 and MLH3, form a heterodimeric complex known as MutL-gamma that is critical for crossing over in mammalian meiosis. This function is highly conserved in the majority of eukaryotes. The Cohen lab has played a central role in elucidating the role of MLH1 and MLH3 in mammals, most recently characterizing mutant mice in which the endonuclease domain of MLH3 is altered to prevent this enzymatic activity (Toledo et al, 2019). Studies are currently underway to determine how MutL-gamma is regulated by CNTD1 and by RFC complex (Gray et al, 2020).