MEIOB targets single-strand DNA and is necessary for meiotic recombination.
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.
Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, UMR 967, Fontenay aux Roses, France ; CEA, DSV, iRCM, SCSR, LDG, Fontenay aux Roses, France ; INSERM, Unité 967, Fontenay aux Roses, France ; Univ. Paris-Sud, UMR 967, Fontenay aux Roses, France.
Benoit
B
Souquet
Emilie
E
Abby
Roxane
R
Hervé
Friederike
F
Finsterbusch
Sophie
S
Tourpin
Ronan
R
Le Bouffant
Clotilde
C
Duquenne
Sébastien
S
Messiaen
Emmanuelle
E
Martini
Jacqueline
J
Bernardino-Sgherri
Attila
A
Toth
René
R
Habert
Gabriel
G
Livera
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D023902:Chromosome Pairing / Q000235:genetics*; D004277:DNA, Single-Stranded / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005854:Germ Cells; D059765:Homologous Recombination / Q000235:genetics*; D006801:Humans; D008297:Male; D008540:Meiosis / Q000235:genetics*; D051379:Mice; D051135:Rad51 Recombinase / Q000235:genetics; D051716:Replication Protein A / Q000235:genetics / Q000378:metabolism; D013090:Spermatocytes / Q000378:metabolism
D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C587161:MEIOB protein, human; C497167:RPA1 protein, human; D051716:Replication Protein A; D051135:Rad51 Recombinase; C074556:DMC1 protein, human