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Proc Natl Acad Sci U S A. 2018 Oct 23;115(43):E10041-E10048. doi: 10.1073/pnas.1810457115. Epub 2018 Oct 9.

Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase.

Author information

1
Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10032.
2
Department of Genetics and Development, Columbia University, New York, NY 10032.
3
Department of Molecular Biophysics and Biochemistry, Yale University School of Medicine, New Haven, CT 06520.
4
Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY 10032; ecg2108@cumc.columbia.edu.

Abstract

Cross-over recombination products are a hallmark of meiosis because they are necessary for accurate chromosome segregation and they also allow for increased genetic diversity during sexual reproduction. However, cross-overs can also cause gross chromosomal rearrangements and are therefore normally down-regulated during mitotic growth. The mechanisms that enhance cross-over product formation upon entry into meiosis remain poorly understood. In Saccharomyces cerevisiae, the Superfamily 1 (Sf1) helicase Srs2, which is an ATP hydrolysis-dependent motor protein that actively dismantles recombination intermediates, promotes synthesis-dependent strand annealing, the result of which is a reduction in cross-over recombination products. Here, we show that the meiosis-specific recombinase Dmc1 is a potent inhibitor of Srs2. Biochemical and single-molecule assays demonstrate that Dmc1 acts by inhibiting Srs2 ATP hydrolysis activity, which prevents the motor protein from undergoing ATP hydrolysis-dependent translocation on Dmc1-bound recombination intermediates. We propose a model in which Dmc1 helps contribute to cross-over formation during meiosis by antagonizing the antirecombinase activity of Srs2.

KEYWORDS:

Dmc1; Rad51; Srs2; homologous recombination; meiosis

PMID:
30301803
PMCID:
PMC6205449
[Available on 2019-04-23]
DOI:
10.1073/pnas.1810457115
[Indexed for MEDLINE]

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