Mek1/Mre4 is a master regulator of meiotic recombination in budding yeast.

Abstract

Sexually reproducing organisms create gametes with half the somatic cell chromosome number so that fusion of gametes at fertilization does not change the ploidy of the cell. This reduction in chromosome number occurs by the specialized cell division of meiosis in which two rounds of chromosome segregation follow a single round of chromosome duplication. Meiotic crossovers formed between the non-sister chromatids of homologous chromosomes, combined with sister chromatid cohesion, physically connect homologs, thereby allowing proper segregation at the first meiotic division. Meiotic recombination is initiated by programmed double strand breaks (DSBs) whose repair is highly regulated such that (1) there is a bias for recombination with homologs rather than sister chromatids, (2) crossovers are distributed throughout the genome by a process called interference, (3) crossover homeostasis regulates the balance between crossover and non-crossover repair to maintain a critical number of crossovers and (4) each pair of homologs receives at least one crossover. It was previously known that the imposition of interhomolog bias in budding yeast requires meiosis-specific modifications to the DNA damage response and the local activation of the meiosis-specific Mek1/Mre4 (hereafter Mek1) kinase at DSBs. However, because inactivation of Mek1 results in intersister, rather than interhomolog DSB repair, whether Mek1 had a role in interhomolog pathway choice was unknown. A recent study by Chen et al. (2015) reveals that Mek1 indirectly regulates the crossover/non-crossover decision between homologs as well as genetic interference. It does this by enabling phosphorylation of Zip1, the meiosis-specific transverse filament protein of the synaptonemal complex (SC), by the conserved cell cycle kinase, Cdc7-Dbf4 (DDK). These results suggest that Mek1 is a “master regulator” of meiotic recombination in budding yeast.