ATR is required to complete meiotic recombination in mice
Pacheco, Sarai (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Maldonado Linares, Andros (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Marcet-Ortega, Marina (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Rojas, Cristina (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Martínez Marchal, Ana (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Fuentes Lazaro, Judit (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Lange, Julian (Memorial Sloan Kettering Cancer Center)
Jasin, Maria (Memorial Sloan Kettering Cancer Center)
Keeney, Scott (Memorial Sloan Kettering Cancer Center)
Fernández-Capetillo, Oscar (Centro Nacional de Investigaciones Oncológicas)
Garcia-Caldés, Montserrat (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Roig, Ignasi (Ignasi) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)

Date:	2018
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.
Grants:	Ministerio de Ciencia e Innovación BFU2016-80370-P Ministerio de Ciencia e Innovación BFU2015-71786-REDT Ministerio de Ciencia e Innovación BFU2013-43965-P Ministerio de Ciencia e Innovación BES-2011-045381 Ministerio de Ciencia e Innovación BFU2010-18965
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Animals ; Ataxia telangiectasia mutated proteins ; Cell cycle proteins ; Checkpoint kinase 1 ; Chromosome pairing ; DNA breaks, Double-stranded ; Homologous recombination ; In situ hybridization, Fluorescence ; Male ; Meiosis ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Nuclear proteins ; Rad51 recombinase ; Spermatocytes ; Testis
Published in:	Nature communications, Vol. 9 (2018) , art. 2622, ISSN 2041-1723

DOI: 10.1038/s41467-018-04851-z
PMID: 29977027

14 p, 6.4 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles