Maintenance of meiotic crossover against reduced double-strand break formation in fission yeast lacking histone H2A.Z.

Meiotic crossover (CO) recombination initiates from programmed DNA double-strand breaks (DSBs) around hotspots, and results in reciprocal exchange of chromosome segments between homologous chromosomes (homologs). COs are crucial for most sexually-reproducing organisms because they promote accurate chromosome segregation and create genetic diversity. Therefore, faithful accomplishment of CO formation is ensured in many ways, but the bases of the regulation are not fully understood. Our previous study using fission yeast has revealed that mutants lacking the conserved histone H2A.Z are defective in DSB formation but maintain CO frequency at three loci tested. Here, we tested five additional sites to show that mutants lacking H2A.Z exhibit normal and increased CO frequency at two and three loci, respectively. Examining one of the CO-increased intervals in the mutant revealed that the CO upregulation is mediated at least partly at a recombination intermediate level. In addition, our genetic as well as genome-wide analyses implied a possibility that, even without H2A.Z, COs are maintained by weak and non-hotspot DSBs, which are processed preferentially as CO. These observations provide clues to further our understanding on CO control.

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