Autori: Holloway J.K., Mohan S., Balmus G., et al.
Editorial: PLoS Genet., 7(6), 2011.
Mutations in genes essential for genome maintenance during meiosis can result in severe disruptions to spermatogenesis and subsequent low fertility and/or birth defects in mammals. The mammalian homolog of yeast plays a critical role in somatic cell repair in mice. Here, we show that this critical function extends to mammalian germ cells, by examining the effects of a Btbd12 gene disruption in mice. Btbd12 mutant mice show severely reduced fertility, as a result of both pre-meiotic spermatogonial proliferation defects and impairment of proper meiotic progression. BTBD12 appears to be required for normal progression of double-strand break repair events that result in the formation of crossovers between maternal and paternal homologous chromosomes, with Btbd12 mutants displaying an increase in unrepaired breaks, impaired homologous chromosome interactions, and a slight increase in the number of crossover intermediates. BTBD12 protein is also down-regulated in the testes of Atm null mice, supporting previous studies showing that BTBD12 is a target of ATM kinase. These data provide new evidence about the role of BTBD12 in mammalian gametogenesis and are critical to furthering the understanding of the molecular processes involved in meiotic DNA repair.
Cuvinte cheie: Slx4, BTBD12, meiosis, DNA damage