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The ATM Signaling Cascade Promotes Recombination-Dependent Pachytene Arrest in Mouse Spermatocytes


Meiosis is the specialized cell division by which haploid cells are produced. As germ cells enter the first meiotic prophase, programmed double-stranded breaks (DSBs) are formed throughout the genome. Repair of these DSBs by homologous recombination is crucial for proper segregation of homologous chromosomes at the end of the first meiotic division, and thus, for the production of haploid gametes. Moreover, failure to correctly repair these DSBs can have deleterious effects on the genomic integrity of offspring. To ensure that meiocytes that fail to repair meiotic DSBs do not complete meiosis, recombination is tightly controlled. However, the signaling pathway(s) tying meiotic recombination to meiotic progression in mouse spermatocytes is not known. We report here that the ATM-signaling pathway, composed of the MRE11 complex, ATM and CHK2, is responsible for activation of the recombination-dependent arrest that occurs in Trip13 mutant mouse spermatocytes, which accumulate unrepaired DSBs during meiotic prophase.


Vyšlo v časopise: The ATM Signaling Cascade Promotes Recombination-Dependent Pachytene Arrest in Mouse Spermatocytes. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005017
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005017

Souhrn

Meiosis is the specialized cell division by which haploid cells are produced. As germ cells enter the first meiotic prophase, programmed double-stranded breaks (DSBs) are formed throughout the genome. Repair of these DSBs by homologous recombination is crucial for proper segregation of homologous chromosomes at the end of the first meiotic division, and thus, for the production of haploid gametes. Moreover, failure to correctly repair these DSBs can have deleterious effects on the genomic integrity of offspring. To ensure that meiocytes that fail to repair meiotic DSBs do not complete meiosis, recombination is tightly controlled. However, the signaling pathway(s) tying meiotic recombination to meiotic progression in mouse spermatocytes is not known. We report here that the ATM-signaling pathway, composed of the MRE11 complex, ATM and CHK2, is responsible for activation of the recombination-dependent arrest that occurs in Trip13 mutant mouse spermatocytes, which accumulate unrepaired DSBs during meiotic prophase.


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