ATR is required to complete meiotic recombination in mice
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, bu...
| Autores: | , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:225213 |
| Acceso en línea: | https://ddd.uab.cat/record/225213 https://dx.doi.org/urn:doi:10.1038/s41467-018-04851-z |
| Access Level: | acceso abierto |
| Palabra clave: | 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 |
| Sumario: | 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. |
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