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The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis

Nature Structural & Molecular Biology volume 18, pages 56–60 (2011)Cite this article

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A Corrigendum to this article was published on 05 February 2013

A Corrigendum to this article was published on 06 September 2011

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Abstract

The ubiquitously expressed Rad51 recombinase and the meiosis-specific Dmc1 recombinase promote the formation of strand-invasion products (D-loops) between homologous molecules. Strand-invasion products are processed by either the double-strand break repair (DSBR) or synthesis-dependent strand annealing (SDSA) pathway. D-loops destined to be processed by SDSA need to dissociate, producing non-crossovers, and those destined for DSBR should resist dissociation to generate crossovers. The mechanism that channels recombination intermediates into different homologous-recombination pathways is unknown. Here we show that D-loops in a human DMC1-driven reaction are substantially more resistant to dissociation by branch-migration proteins such as RAD54 than those formed by RAD51. We propose that the intrinsic resistance to dissociation of DMC1 strand-invasion intermediates may account for why DMC1 is essential to ensure the proper segregation of chromosomes in meiosis.

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Figure 1: Pathways of homologous recombination.
Figure 2: RAD54 does not dissociate non-deproteinized joint molecules (D-loops) formed by DMC1.
Figure 3: RAD54 dissociates native D-loops formed by RAD51, but not DMC1, in the presence of Hop2–Mnd1.

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Change history

  • 09 August 2011

    In the version of this article initially published, the legend for Figure 2d,e did not include the source of the data in those panels. These data originally appeared in ref. 20. The error has been corrected in the HTML and PDF versions of the article.

  • 10 October 2012

    In the version of this article initially published, support from the Oklahoma Center for the Advancement of Science and Technology to R.J.P. was not acknowledged. The error has been corrected in the PDF and HTML versions of this article.

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Acknowledgements

We thank P. Sung (Yale University) and W. Holloman (Cornell University) for RAD51 and BLM expression vectors, members of the Camerini-Otero and Mazin labs for comments and discussion, and M. Lichten and P. Hsieh for critical reading of this manuscript. This work was supported by US National Institutes of Health grants CA100839 and MH084119, the Leukemia and Lymphoma Society Scholar Award 1054-09 (to A.V.M.), the Oklahoma Center for the Advancement of Science and Technology Project HR10-048S (to R.J.P.) and the Intramural Research Program of the US National Institute of Diabetes and Digestive and Kidney Diseases (to R.D.C.-O.).

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Author notes

  1. Roberto J Pezza

    Present address: Current address: Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA.,

  2. Dmitry V Bugreev and Roberto J Pezza: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Dmitry V Bugreev, Olga M Mazina & Alexander V Mazin

  2. Genetics and Biochemistry Branch, National Institute of Diabetes and Digestive and Kidney Diseases, US National Institutes of Health, Bethesda, Maryland, USA

    Roberto J Pezza, Oleg N Voloshin & R Daniel Camerini-Otero

  3. Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Science, Novosibirsk, Russia

    Alexander V Mazin

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  1. Dmitry V Bugreev
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Contributions

D.V.B., R.J.P., A.V.M. and R.D.C.-O. conceived the general ideas for this study. All authors planned experiments and interpreted data. D.V.B., R.J.P., O.N.V. and O.M.M. performed experiments. A.V.M. and R.D.C.-O. wrote the manuscript, and all authors provided editorial input.

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Correspondence to R Daniel Camerini-Otero or Alexander V Mazin.

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Bugreev, D., Pezza, R., Mazina, O. et al. The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis. Nat Struct Mol Biol 18, 56–60 (2011). https://doi.org/10.1038/nsmb.1946

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