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The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination

Nature Structural & Molecular Biology volume 12, pages 449–453 (2005)Cite this article

Abstract

During the first meiotic division, homologous chromosomes (homologs) have to separate to opposite poles of the cell to ensure the right complement in the progeny. Homologous recombination provides a mechanism for a genome-wide homology search and physical linkage among the homologs before their orderly segregation. Rad51 and Dmc1 recombinases are the major players in these processes. Disruption of meiosis-specific HOP2 or MND1 genes leads to severe defects in homologous synapsis and an early-stage recombination failure resulting in sterility. Here we show that mouse Hop2 can efficiently form D-loops, the first recombination intermediates, but this activity is abrogated upon association with Mnd1. Furthermore, the Hop2–Mnd1 heterodimer physically interacts with Rad51 and Dmc1 recombinases and stimulates their activity up to 35-fold. Our data reveal an interplay among Hop2, Mnd1 and Rad51 and Dmc1 in the formation of the first recombination intermediates during meiosis.

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Figure 1: The mouse Hop2 protein promotes D-loop formation.
Figure 2: The Hop2–Mnd1 complex stimulates D-loop formation mediated by Dmc1 and Rad51 proteins.
Figure 3: Functional interaction of Hop2, Mnd1, Rad51 and Dmc1 proteins.
Figure 4: The role of the Hop2–Mnd1 proteins in recombination.

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Acknowledgements

J.Y.M. is a Canadian Institutes of Health Research new investigator and this work is supported by grants from the National Cancer Institute of Canada and the National Science and Engineering Research Council of Canada. We thank O. Voloshin for the RecA protein, P. Romanienko for the Hop2 cDNA, and P. Hsieh, M. Lichten and O. Voloshin for valuable comments on the manuscript.

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Authors and Affiliations

  1. Genetics and Biochemistry Branch, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, 5 Memorial Drive, Bethesda, 20892, Maryland, USA

    Galina V Petukhova, Roberto J Pezza, Filip Vanevski & R Daniel Camerini-Otero

  2. Genome Stability Laboratory, Laval University Cancer Research Center, 9 McMahon Street, Québec City, G1R 2J6, Québec, Canada

    Mickael Ploquin & Jean-Yves Masson

Authors
  1. Galina V Petukhova
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Correspondence to R Daniel Camerini-Otero.

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Supplementary information

Supplementary Fig. 1

DNA binding of Hop2–Mnd1 complex. (PDF 280 kb)

Supplementary Fig. 2

Single-strand annealing activity is not sufficient for D-loop formation. (PDF 1038 kb)

Supplementary Fig. 3

Hop2 does not denature dsDNA. (PDF 1371 kb)

Supplementary Methods (PDF 22 kb)

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Petukhova, G., Pezza, R., Vanevski, F. et al. The Hop2 and Mnd1 proteins act in concert with Rad51 and Dmc1 in meiotic recombination. Nat Struct Mol Biol 12, 449–453 (2005). https://doi.org/10.1038/nsmb923

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