Multiple 9-1-1 complexes promote homolog synapsis, DSB repair, and ATR signaling during mammalian meiosisMore about Open Access at the Crick
Authors listCatalina Pereira Gerardo A Arroyo-Martinez Matthew Z Guo Michael S Downey Emma R Kelly Kathryn J Grive Shantha Mahadevaiah Jennie R Sims Vitor M Faca Charlton Tsai Carl J Schiltz Niek Wit Heinz Jacobs Nathan L Clark Raimundo Freire James Turner Amy M Lyndaker Miguel A Brieno-Enriquez Paula E Cohen Marcus B Smolka Robert S Weiss
DNA damage response mechanisms have meiotic roles that ensure successful gamete formation. While completion of meiotic double-strand break (DSB) repair requires the canonical RAD9A-RAD1-HUS1 (9A-1-1) complex, mammalian meiocytes also express RAD9A and HUS1 paralogs, RAD9B and HUS1B, predicted to form alternative 9-1-1 complexes. The RAD1 subunit is shared by all predicted 9-1-1 complexes and localizes to meiotic chromosomes even in the absence of HUS1 and RAD9A. Here, we report that testis-specific disruption of RAD1 in mice resulted in impaired DSB repair, germ cell depletion, and infertility. Unlike Hus1 or Rad9a disruption, Rad1 loss in meiocytes also caused severe defects in homolog synapsis, impaired phosphorylation of ATR targets such as H2AX, CHK1, and HORMAD2, and compromised meiotic sex chromosome inactivation. Together, these results establish critical roles for both canonical and alternative 9-1-1 complexes in meiotic ATR activation and successful prophase I completion.
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Publisher website (DOI) 10.7554/eLife.68677
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Europe PubMed Central 35133274
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