ATR is required to complete meiotic recombination in mice

Sarai Pacheco, Andros Maldonado-Linares, Marina Marcet-Ortega, Cristina Rojas, Ana Martinez-Marchal, Judit Fuentes-Lazaro, Julian Lange, Maria Jasin, Scott Keeney, Oscar Fernandez-Capetillo, Montserrat Garcia-Caldes, Ignasi Roig

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13 Citations (Scopus)

Abstract

© 2018 The Author(s). 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.
Original languageEnglish
Article number61
Pages (from-to)-
JournalNature Communications
Volume9
DOIs
Publication statusPublished - 1 Dec 2018

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    Pacheco, S., Maldonado-Linares, A., Marcet-Ortega, M., Rojas, C., Martinez-Marchal, A., Fuentes-Lazaro, J., Lange, J., Jasin, M., Keeney, S., Fernandez-Capetillo, O., Garcia-Caldes, M., & Roig, I. (2018). ATR is required to complete meiotic recombination in mice. Nature Communications, 9, -. [61]. https://doi.org/10.1038/s41467-018-04851-z