van Overbeek, M. | bioRxiv Science

bioRxiv2019

Ensuring meiotic DNA break formation in the mouse pseudoautosomal region

Sex chromosomes in males share only a diminutive homologous segment, the pseudoautosomal region (PAR), wherein meiotic double-strand breaks (DSBs), pairing, and crossing over must occur for correct segregation. How cells ensure PAR recombination is unknown. Here we delineate cis-and trans-acting factors that control PAR ultrastructure and make the PAR the hottest area of DSB formation in the male mouse genome. Prior to DSB formation, PAR chromosome axes elongate, sister chromatids separate, and DSB-promoting factors hyperaccumulate. These phenomena are linked to mo-2 minisatellite arrays and require ANKRD31 protein. We propose that the repetitive PAR sequence confers unique chromatin and higher order structures crucial for DSB formation, X-Y pairing, and recombination. Our findings establish a mechanistic paradigm of mammalian sex chromosome segregation during spermatogenesis.

molecular biology↗

bioRxiv2018

Multilayered mechanisms ensure that short chromosomes recombine in meiosis

To segregate accurately during meiosis, homologous chromosomes in most species must recombine. Very small chromosomes would risk missegregation if recombination were randomly distributed, so the double-strand breaks (DSBs) that initiate recombination are not haphazard. How this nonrandomness is controlled is not under-stood. Here we demonstrate that Saccharomyces cerevisiae integrates multiple, temporally distinct pathways to regulate chromosomal binding of pro-DSB factors Rec114 and Mer2, thereby controlling duration of a DSB-competent state. Homologous chromosome engagement regulates Rec114/Mer2 dissociation late in prophase, whereas replication timing and proximity to centromeres or telomeres influence timing and amount of Rec114/Mer2 accumulation early. A distinct early mechanism boosts Rec114/Mer2 binding quickly to high levels specifically on the shortest chromosomes, dependent on chromosome axis proteins and subject to selection pressure to maintain hyperrecombinogenic properties of these chromosomes. Thus, an organisms karyotype and its attendant risk of meiotic missegregation influence the shape and evolution of its recombination landscape.

genetics↗