ATR is required to complete meiotic recombination in mice

Sarai Pacheco, Andros Maldonado-Linares, Marina Marcet-Ortega, Cristina Rojas, Ana Martínez-Marchal, Judit Fuentes-Lazaro, Julian Lange, Maria Jasin, Scott Keeney, Oscar Fernández-Capetillo, Montserrat Garcia-Caldés and Ignasi Roig ()
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Sarai Pacheco: Universitat Autònoma de Barcelona
Andros Maldonado-Linares: Universitat Autònoma de Barcelona
Marina Marcet-Ortega: Universitat Autònoma de Barcelona
Cristina Rojas: Universitat Autònoma de Barcelona
Ana Martínez-Marchal: Universitat Autònoma de Barcelona
Judit Fuentes-Lazaro: Universitat Autònoma de Barcelona
Julian Lange: Memorial Sloan Kettering Cancer Center
Maria Jasin: Memorial Sloan Kettering Cancer Center
Scott Keeney: Memorial Sloan Kettering Cancer Center
Oscar Fernández-Capetillo: Spanish National Cancer Research Centre
Montserrat Garcia-Caldés: Universitat Autònoma de Barcelona
Ignasi Roig: Universitat Autònoma de Barcelona

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Precise execution of recombination during meiosis is essential for forming chromosomally-balanced gametes. Meiotic recombination initiates with the formation and resection of DNA double-strand breaks (DSBs). Cellular responses to meiotic DSBs are critical for efficient repair and quality control, but molecular features of these remain poorly understood, particularly in mammals. Here we report that the DNA damage response protein kinase ATR is crucial for meiotic recombination and completion of meiotic prophase in mice. Using a hypomorphic Atr mutation and pharmacological inhibition of ATR in vivo and in cultured spermatocytes, we show that ATR, through its effector kinase CHK1, promotes efficient RAD51 and DMC1 assembly at RPA-coated resected DSB sites and establishment of interhomolog connections during meiosis. Furthermore, our findings suggest that ATR promotes local accumulation of recombination markers on unsynapsed axes during meiotic prophase to favor homologous chromosome synapsis. These data reveal that ATR plays multiple roles in mammalian meiotic recombination.

Date: 2018
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DOI: 10.1038/s41467-018-04851-z

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