Dataset Information

MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination.

ABSTRACT: Meiotic recombination enables the reciprocal exchange of genetic material between parental homologous chromosomes, and ensures faithful chromosome segregation during meiosis in sexually reproducing organisms. This process relies on the complex interaction of DNA repair factors and many steps remain poorly understood in mammals. Here we report the identification of MEIOB, a meiosis-specific protein, in a proteomics screen for novel meiotic chromatin-associated proteins in mice. MEIOB contains an OB domain with homology to one of the RPA1 OB folds. MEIOB binds to single-stranded DNA and exhibits 3'-5' exonuclease activity. MEIOB forms a complex with RPA and with SPATA22, and these three proteins co-localize in foci that are associated with meiotic chromosomes. Strikingly, chromatin localization and stability of MEIOB depends on SPATA22 and vice versa. Meiob-null mouse mutants exhibit a failure in meiosis and sterility in both sexes. Our results suggest that MEIOB is required for meiotic recombination and chromosomal synapsis.

SUBMITTER: Luo M

PROVIDER: S-EPMC3891831 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination.

Luo Mengcheng M Yang Fang F Leu N Adrian NA Landaiche Jessica J Handel Mary Ann MA Benavente Ricardo R La Salle Sophie S Wang P Jeremy PJ

Nature communications 20130101

Meiotic recombination enables the reciprocal exchange of genetic material between parental homologous chromosomes, and ensures faithful chromosome segregation during meiosis in sexually reproducing organisms. This process relies on the complex interaction of DNA repair factors and many steps remain poorly understood in mammals. Here we report the identification of MEIOB, a meiosis-specific protein, in a proteomics screen for novel meiotic chromatin-associated proteins in mice. MEIOB contains an ...[more]

PMID: 24240703

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Project description:During meiosis, self-inflicted DNA double-strand breaks (DSBs) are created by the protein Spo11 and repaired by homologous recombination leading to gene conversions and crossovers. Crossover formation is vital for the segregation of homologous chromosomes during the first meiotic division and requires the RecA orthologue, Dmc1. We analyzed repair during meiosis of site-specific DSBs created by another nuclease, VMA1-derived endonuclease (VDE), in cells lacking Dmc1 strand-exchange protein. Turnover and resection of the VDE-DSBs was assessed in two different reporter cassettes that can repair using flanking direct repeat sequences, thereby obviating the need for a Dmc1-dependent DNA strand invasion step. Access of the single-strand binding complex replication protein A, which is normally used in all modes of DSB repair, was checked in chromatin immunoprecipitation experiments, using antibody against Rfa1. Repair of the VDE-DSBs was severely inhibited in dmc1Delta cells, a defect that was associated with a reduction in the long tract resection required to initiate single-strand annealing between the flanking repeat sequences. Mutants that either reduce Spo11-DSB formation or abolish resection at Spo11-DSBs rescued the repair block. We also found that a replication protein A component, Rfa1, does not accumulate to expected levels at unrepaired single-stranded DNA (ssDNA) in dmc1Delta cells. The requirement of Dmc1 for VDE-DSB repair using flanking repeats appears to be caused by the accumulation of large quantities of ssDNA that accumulate at Spo11-DSBs when Dmc1 is absent. We propose that these resected DSBs sequester both resection machinery and ssDNA binding proteins, which in wild-type cells would normally be recycled as Spo11-DSBs repair. The implication is that repair proteins are in limited supply, and this could reflect an underlying mechanism for regulating DSB repair in wild-type cells, providing protection from potentially harmful effects of overabundant repair proteins.

Dataset Information

MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination.

Publications

MEIOB exhibits single-stranded DNA-binding and exonuclease activities and is essential for meiotic recombination.

Similar Datasets

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