MEIOB targets single-strand DNA and is necessary for meiotic recombination

PLoS Genet. 2013;9(9):e1003784. doi: 10.1371/journal.pgen.1003784. Epub 2013 Sep 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Chromosome Pairing / genetics*
  • DNA, Single-Stranded / genetics*
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Female
  • Germ Cells
  • Homologous Recombination / genetics*
  • Humans
  • Male
  • Meiosis / genetics*
  • Mice
  • Rad51 Recombinase / genetics
  • Replication Protein A / genetics
  • Replication Protein A / metabolism
  • Spermatocytes / metabolism

Substances

  • Cell Cycle Proteins
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • MEIOB protein, human
  • RPA1 protein, human
  • Replication Protein A
  • Rad51 Recombinase
  • DMC1 protein, human

Grants and funding

This work was funded in part by the ANR grant (#1239 03) and supported by the Université Paris Diderot-Paris 7, Commissariat à l'Energie Atomique (CEA), Institut National de la Santé et de la Recherche Médicale (INSERM). BS holds a fellowship from the Région Ile-de-France–DIM Stem Pôle, AE holds a fellowship from Irtelis (CEA), FF was supported by Deutsche Forschungsgemeinschaft (DFG): SPP1384 TO 421/4-2 and AT. was supported by DFG Heisenberg fellowship TO 421/5-1. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.