The formation and repair of DNA double-strand breaks in mammalian meiosis

Programmed DNA double-strand breaks (DSBs) are necessary for meiosis in mammals. A sufficient number of DSBs ensure the normal pairing/synapsis of homologous chromosomes. Abnormal DSB repair undermines meiosis, leading to sterility in mammals. The DSBs that initiate recombination are repaired as crossovers and noncrossovers, and crossovers are required for correct chromosome separation. Thus, the placement, timing, and frequency of crossover formation must be tightly controlled. Importantly, mutations in many genes related to the formation and repair of DSB result in infertility in humans. These mutations cause nonobstructive azoospermia in men, premature ovarian insufficiency and ovarian dysgenesis in women. Here, we have illustrated the formation and repair of DSB in mammals, summarized major factors influencing the formation of DSB and the theories of crossover regulation.

Automated summary

Programmed DNA double-strand breaks (DSBs) are essential for meiosis in mammals, with abnormal repair leading to infertility. Recombination of DSBs occurs as crossovers and noncrossovers, with crossovers playing a critical role in correct chromosome separation. Mutations in genes related to DSB formation and repair can result in infertility, affecting sperm production in men and ovarian function in women.