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

Dmitry V. Bugreev; Roberto J. Pezza; Olga M. Mazina; Oleg N. Voloshin; R. Daniel Camerini-Otero; Alexander V. Mazin

doi:10.1038/nsmb.1946

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

Dmitry V. Bugreev, Roberto J. Pezza, Olga M. Mazina, Oleg N. Voloshin, R. Daniel Camerini-Otero, Alexander V. Mazin

Research output: Contribution to journal › Article › peer-review

44 Scopus citations

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.

Original language	English (US)
Pages (from-to)	56-61
Number of pages	6
Journal	Nature Structural and Molecular Biology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1038/nsmb.1946
State	Published - Jan 2011
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Structural Biology

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@article{33031ed3141d455aa3f5c730cff3cada,

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

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.",

author = "Bugreev, {Dmitry V.} and Pezza, {Roberto J.} and Mazina, {Olga M.} and Voloshin, {Oleg N.} and Camerini-Otero, {R. Daniel} and Mazin, {Alexander V.}",

note = "Funding Information: 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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AU - Bugreev, Dmitry V.

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AU - Mazina, Olga M.

AU - Voloshin, Oleg N.

AU - Camerini-Otero, R. Daniel

AU - Mazin, Alexander V.

N1 - Funding Information: 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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N2 - 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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The resistance of DMC1 D-loops to dissociation may account for the DMC1 requirement in meiosis

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