Preprint links PRDM9 binding symmetry and meiotic double-strand break repair to large-scale spermatogenesis disruption

A preprint posted to bioRxiv examines the mechanisms by which mutations affecting meiotic double-strand break (DSB) repair produce large-scale disruptions to spermatogenesis in mammalian models. The work centres on PRDM9, a histone methyltransferase that specifies the genomic positions at which programmed DSBs form during meiosis — a step essential for homologous chromosome pairing and recombination.

The authors investigate how the symmetry of PRDM9 binding — whether PRDM9 targets the same genomic positions on both homologous chromosomes — influences the efficiency of homology search and subsequent DSB repair. Prior work has established that asymmetric PRDM9 binding, where the two homologues carry different sequence variants at a binding site, impairs homologue pairing; the current preprint extends this framework by characterising downstream spermatogenic phenotypes when key repair pathway components are genetically perturbed.

PRDM9 is described as the most rapidly evolving protein in mammals, and variation in its zinc-finger DNA-binding domain has been associated with hybrid sterility in mice as well as with recombination rate variation more broadly. The findings contribute to understanding of meiotic failure as a cause of male infertility and have broader implications for models of recombination and genome stability.

This is a preprint that has not yet undergone peer review.