PLoS Genetics · 2013 · 125 citations · 56 references
Life SciencesGeneticsMolecular BiologyDna RepairInfertilityReproductive BiologyHomologous RecombinationMeiosis In Germ CellsMeiotic RecombinationRecombination ProteinsSpermatogenesis GeneticsChromosome AxesDmc1 ProteinDmc1 RegulationDna Strand Break RepairMeiotic Recombination FociMeiotic Recombination ProteinsRepair Of Meiotic Double-strand BreaksSingle-strand Dna Binding Proteins
Meiotic recombination is a mandatory process for sexual reproduction. We identified a protein specifically implicated in meiotic homologous recombination that we named: meiosis specific with OB domain (MEIOB). This protein is conserved among metazoan species and contains single-strand DNA binding sites similar to those of RPA1. Our studies in vitro revealed that both recombinant and endogenous MEIOB can be retained on single-strand DNA. Those in vivo demonstrated the specific expression of Meiob in early meiotic germ cells and the co-localization of MEIOB protein with RPA on chromosome axes. MEIOB localization in Dmc1 (-/-) spermatocytes indicated that it accumulates on resected DNA. Homologous Meiob deletion in mice caused infertility in both sexes, due to a meiotic arrest at a zygotene/pachytene-like stage. DNA double strand break repair and homologous chromosome synapsis were impaired in Meiob (-/-) meiocytes. Interestingly MEIOB appeared to be dispensable for the initial loading of recombinases but was required to maintain a proper number of RAD51 and DMC1 foci beyond the zygotene stage. In light of these findings, we propose that RPA and this new single-strand DNA binding protein MEIOB, are essential to ensure the proper stabilization of recombinases which is required for successful homology search and meiotic recombination.
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