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Genes Dev. 2019 Sep 1;33(17-18):1191-1207. doi: 10.1101/gad.328062.119. Epub 2019 Aug 1.

Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination.

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Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, New York 10032, USA.
DSB Repair Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom.
Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, USA.
Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York 10032, USA.
Center for Quantitative Biology, Peking University-Tsinghua University Joint Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
Contributed equally


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.


DNA repair; Dmc1; Rad51; homologous recombination; meiosis


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