Abstract
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.
Highlights
Meiosis is a central process of sexual reproduction
Our findings indicate that meiosis specific with oligonucleotide binding (OB) domain (MEIOB) binds Single-strand DNA (ssDNA), and we propose that MEIOB is a meiotic paralog of replication protein A (RPA), another OB-domain containing protein
The orthologs of the Meiob group formed a family distinct from the Rpa1 group (Figure 1A, phylogenetic tree of MEIOB and RPA1 using MULTALIN) [23]. These data suggest that Meiob may have evolved from an ancestral Rpa1 shortly before the appearance of multicellularity
Summary
Meiosis is a central process of sexual reproduction. This specialized cell division program allows halving the genome of diploid germ cells to produce haploid gametes. Meiotic recombination differs from mitotic recombination in that it uses a chromatid from the homolog instead of the sister chromatid as a template for repair [2] It favors CO formation and involves specific proteins [3]. The decision to form or not a CO is thought to be made before or during strand invasion of the homologous chromosome [8] This being the case, the nature and the regulation of proteins loaded at broken ends is likely to be important for the outcome of the DSBs. Single-strand DNA (ssDNA) formed during DNA metabolism is coated by the trimeric replication protein A (RPA) complex (composed of RPA1 70 kDa, RPA2 32 kDa, RPA3 14 kDa) serving to protect from degradation and to prevent secondary structure formation. The presence of BRCA2, which directly interacts with RAD51 and DMC1, is necessary for Author Summary
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