Two auxiliary factors promote Dmc1-driven DNA strand exchange via stepwise mechanisms

Significance Homologous recombination (HR) is highly induced during meiosis as it plays an essential role in segregating chromosomes at the first division of meiosis. Dmc1 is the major enzyme responsible for homology searching and strand exchange in meiosis. However, in the cell, Dmc1 cannot function without two major auxiliary factors, Hop2-Mnd1 and Swi5-Sfr1. How these auxiliary factors collaborate to facilitate Dmc1’s activity remained elusive. Here, we demonstrate that Hop2-Mnd1 allows Dmc1 to access and initiate strand invasion into homologous dsDNA while Swi5-Sfr1 acts to stabilize Dmc1 binding to single-stranded DNA and promote strand exchange with Hop2-Mnd1. Thus, our findings provide fundamental insights into the mechanism of meiotic HR, which is central to inheritance and evolution.