ATR is a multifunctional regulator of male mouse meiosis
Widger, Alexander (The Francis Crick Institute)
Mahadevaiah, Shantha K. (Francis Crick Institute)
Lange, Julian (Memorial Sloan Kettering Cancer Center)
Elinati, Elias (The Francis Crick Institute)
Zohren, Jasmin (The Francis Crick Institute)
Hirota, Takayuki (The Francis Crick Institute)
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")
Stanzione, Marcello (TU Dresden. Faculty of Medicine)
Ojarikre, Obah (The Francis Crick Institute)
Maciulyte, Valdone (The Francis Crick Institute)
De Rooij, Dirk G.. (University of Amsterdam. Center for Reproductive Medicine)
Tóth, Attila (TU Dresden. Faculty of Medicine)
Roig, Ignasi (Ignasi) (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Keeney, Scott (Memorial Sloan Kettering Cancer Center)
Turner, James M. A. (Francis Crick Institute)

Fecha:	2018
Resumen:	Meiotic cells undergo genetic exchange between homologs through programmed DNA double-strand break (DSB) formation, recombination and synapsis. In mice, the DNA damage-regulated phosphatidylinositol-3-kinase-like kinase (PIKK) ATM regulates all of these processes. However, the meiotic functions of the PIKK ATR have remained elusive, because germline-specific depletion of this kinase is challenging. Here we uncover roles for ATR in male mouse prophase I progression. ATR deletion causes chromosome axis fragmentation and germ cell elimination at mid pachynema. This elimination cannot be rescued by deletion of ATM and the third DNA damage-regulated PIKK, PRKDC, consistent with the existence of a PIKK-independent surveillance mechanism in the mammalian germline. ATR is required for synapsis, in a manner genetically dissociable from DSB formation. ATR also regulates loading of recombinases RAD51 and DMC1 to DSBs and recombination focus dynamics on synapsed and asynapsed chromosomes. Our studies reveal ATR as a critical regulator of mouse meiosis.
Ayudas:	Ministerio de Ciencia e Innovación BFU2016-80370-P
Derechos:	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.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Animals ; Ataxia Telangiectasia Mutated Proteins ; Cell Cycle Proteins ; Chromosome Pairing ; Chromosomes, Mammalian ; DNA Breaks, Double-Stranded ; In Situ Hybridization, Fluorescence ; Male ; Meiosis ; Meiotic Prophase I ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Nuclear Proteins ; Rad51 Recombinase ; Spermatocytes
Publicado en:	Nature communications, Vol. 9 (2018) , art. 2621, ISSN 2041-1723

DOI: 10.1038/s41467-018-04850-0
PMID: 29976923

12 p, 7.0 MB

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