ATR is required to complete meiotic recombination in mice Journal Article

Authors: Pacheco, S.; Maldonado-Linares, A.; Marcet-Ortega, M.; Rojas, C.; Martínez-Marchal, A.; Fuentes-Lazaro, J.; Lange, J.; Jasin, M.; Keeney, S.; Fernández-Capetillo, O.; Garcia-Caldés, M.; Roig, I.
Article Title: ATR is required to complete meiotic recombination in mice
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. © 2018 The Author(s).
Keywords: mammalia; mus; synapsis
Journal Title: Nature Communications
Volume: 9
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2018-07-05
Start Page: 2622
Language: English
DOI: 10.1038/s41467-018-04851-z
PROVIDER: scopus
PMCID: PMC6033890
PUBMED: 29977027
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
Citation Impact
MSK Authors
  1. Scott N Keeney
    121 Keeney
  2. Julian Lange
    18 Lange
  3. Maria Jasin
    238 Jasin