Ensuring meiotic DNA break formation in the mouse pseudoautosomal region

Sex chromosomes in males of most eutherian species share only a diminutive homologous segment, the pseudoautosomal region (PAR), wherein double-strand break (DSB) formation, pairing, and crossing over must occur for correct meiotic segregation(1,2). How cells ensure PAR recombination is unknown. Here we delineate an unexpected dynamic ultrastructure of the PAR and identify controlling cis- and trans-acting factors that make this the hottest area of DSB formation in the male mouse genome. Before break formation, multiple DSB-promoting factors hyper-accumulate in the PAR, its chromosome axes elongate, and the sister chromatids separate. These phenomena are linked to heterochromatic mo-2 minisatellite arrays and require MEI4 and ANKRD31 proteins but not axis components REC8 or HORMAD1. We propose that the repetitive PAR sequence confers unique chromatin and higher order structures crucial for recombination. Chromosome synapsis triggers collapse of the elongated PAR structure and, remarkably, oocytes can be reprogrammed to display spermatocyte-like PAR DSB levels simply by delaying or preventing synapsis. Thus, sexually dimorphic behavior of the PAR rests in part on kinetic differences between the sexes for a race between maturation of PAR structure, DSB formation, and completion of pairing and synapsis. Our findings establish a mechanistic paradigm of sex chromosome recombination during meiosis.