Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination
- Justin B. Steinfeld1,8,
- Ondrej Beláň2,8,
- Youngho Kwon3,
- Tsuyoshi Terakawa1,7,
- Amr Al-Zain4,
- Michael J. Smith5,
- J. Brooks Crickard1,
- Zhi Qi6,
- Weixing Zhao3,
- Rodney Rothstein5,
- Lorraine S. Symington4,
- Patrick Sung3,
- Simon J. Boulton2 and
- Eric C. Greene1
- 1Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, New York 10032, USA;
- 2DSB Repair Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom;
- 3Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA;
- 4Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, USA;
- 5Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York 10032, USA;
- 6Center for Quantitative Biology, Peking University-Tsinghua University Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
- Corresponding authors: ecg2108{at}cumc.columbia.edu, simon.boulton{at}crick.ac.uk
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↵8 These authors contributed equally to this work.
Abstract
The vast majority of eukaryotes possess two DNA recombinases: Rad51, which is ubiquitously expressed, and Dmc1, which is meiosis-specific. The evolutionary origins of this two-recombinase system remain poorly understood. Interestingly, Dmc1 can stabilize mismatch-containing base triplets, whereas Rad51 cannot. Here, we demonstrate that this difference can be attributed to three amino acids conserved only within the Dmc1 lineage of the Rad51/RecA family. Chimeric Rad51 mutants harboring Dmc1-specific amino acids gain the ability to stabilize heteroduplex DNA joints with mismatch-containing base triplets, whereas Dmc1 mutants with Rad51-specific amino acids lose this ability. Remarkably, RAD-51 from Caenorhabditis elegans, an organism without Dmc1, has acquired “Dmc1-like” amino acids. Chimeric C. elegans RAD-51 harboring “canonical” Rad51 amino acids gives rise to toxic recombination intermediates, which must be actively dismantled to permit normal meiotic progression. We propose that Dmc1 lineage-specific amino acids involved in the stabilization of heteroduplex DNA joints with mismatch-containing base triplets may contribute to normal meiotic recombination.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.328062.119.
- Received April 25, 2019.
- Accepted July 1, 2019.
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