By: Koodali T. Nishant, Amamah Farzlin Farnaz, Sameer Joshi, Praseetha Sarath, Girija Jogwar
Author summary Meiotic cells rely on carefully orchestrated DNA exchanges, called crossovers, to ensure genetic diversity and accurate chromosome segregation. In budding yeast and mammals, most crossovers are formed from the repair of DNA breaks by the Class I pathway, involving the mismatch repair-related proteins Msh4-Msh5. A second pathway (Class II), involving the Mms4-Mus81 complex, produces a smaller number of crossovers. In this study, we mapped for the first time the Mms4 binding sites across the entire budding yeast genome during meiosis. Surprisingly, Mms4 showed a trend towards binding weak DNA break sites, unlike Msh5 which favored strong DNA break sites. Strikingly, this trend was maintained even when Msh5 was absent. These studies suggest that while there is overlap in their distributions, the two pathways do not compete for the same DNA break sites. We also found that the chromosomal association of Mms4 does not require the formation of meiotic DNA breaks and is primarily associated with axis regions positioned near recombination intermediates. Mms4 binding is also relatively insensitive to sequence polymorphisms at DNA break sites, unlike Msh5. These findings indicate that Mms4-Mus81 provides resilience by repairing meiotic DNA breaks that are processed less efficiently by the Class I pathway.
