Repair of Meiotic DNA Breaks and Homolog Pairing in Mouse Meiosis Requires a Minichromosome Maintenance (MCM) Paralog.
| Autor: | McNairn AJ; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853., Rinaldi VD; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853., Schimenti JC; Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853 jcs92@cornell.edu. |
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| Jazyk: | angličtina |
| Zdroj: | Genetics [Genetics] 2017 Feb; Vol. 205 (2), pp. 529-537. Date of Electronic Publication: 2016 Dec 16. |
| DOI: | 10.1534/genetics.116.196808 |
| Abstrakt: | The mammalian Mcm-domain containing 2 (Mcmdc2) gene encodes a protein of unknown function that is homologous to the minichromosome maintenance family of DNA replication licensing and helicase factors. Drosophila melanogaster contains two separate genes, the Mei-MCMs, which appear to have arisen from a single ancestral Mcmdc2 gene. The Mei-MCMs are involved in promoting meiotic crossovers by blocking the anticrossover activity of BLM helicase, a function presumably performed by MSH4 and MSH5 in metazoans. Here, we report that MCMDC2-deficient mice of both sexes are viable but sterile. Males fail to produce spermatozoa, and formation of primordial follicles is disrupted in females. Histology and immunocytological analyses of mutant testes revealed that meiosis is arrested in prophase I, and is characterized by persistent meiotic double-stranded DNA breaks (DSBs), failure of homologous chromosome synapsis and XY body formation, and an absence of crossing over. These phenotypes resembled those of MSH4/5-deficient meiocytes. The data indicate that MCMDC2 is essential for invasion of homologous sequences by RAD51- and DMC1-coated single-stranded DNA filaments, or stabilization of recombination intermediates following strand invasion, both of which are needed to drive stable homolog pairing and DSB repair via recombination in mice. (Copyright © 2017 by the Genetics Society of America.) |
| Databáze: | MEDLINE |
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