2026-06-30T03:03:29Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/83492024-11-29T13:55:52Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597
Repisalud
author
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
funder
Ministerio de Ciencia e Innovación (España)
funder
American Cancer Society
funder
Howard Hughes Medical Institute
funder
National Institutes of Health (Estados Unidos)
2019-09-16T10:27:58Z
2019-09-16T10:27:58Z
2018-07-05
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
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.
eng
ATR is required to complete meiotic recombination in mice
journal article
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ATRisrequiredtocompletemeiotic_2018.pdf
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ATRisrequiredtocompletemeiotic_supl_2018.pdf
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