Mechanism and regulation of meiotic double-strand break formation in mammals

Programmed DNA double-strand breaks (DSBs) catalyzed by the conserved topoisomerase-like complex SPO11-TOP6BL, together with its accessory proteins, initiate meiotic recombination, a process central to meiosis. In mammals, DSBs are distributed nonrandomly at preferential genomic sites (called hotspots) defined largely by the meiosis-specific protein PRDM9. Precise temporal and spatial control of DSB formation is essential for generating genetic diversity while maintaining genomic stability during meiosis. Disruption of this process leads to aberrant recombination, chromosome mis-segregation, and reproductive defects. In this review, we summarize recent genetic, biochemical, and structural advances clarifying the molecular architecture and regulation of meiotic DSB formation in mammals.