2026-06-30T03:03:40Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/83492024-11-29T13:55:52Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Pacheco, Sarai author Maldonado-Linares, Andros author Marcet-Ortega, Marina author Rojas, Cristina author Martínez-Marchal, Ana author Fuentes-Lazaro, Judit author Lange, Julian author Jasin, Maria author Keeney, Scott author Fernandez-Capetillo, Oscar author Garcia-Caldés, Montserrat author Roig, Ignasi author 2018-07-05 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. Nat Commun. 2018;9(1):2622. 10.1038/s41467-018-04851-z 2041-1723 2041-1723 Nature communications 29977027 http://hdl.handle.net/20.500.12105/8349 ATR is required to complete meiotic recombination in mice