Format

Send to

Choose Destination
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.

Author information

1
Department of Biochemistry and Molecular Biophysics, Columbia University Irving Medical Center, New York, New York 10032, USA.
2
DSB Repair Metabolism Laboratory, The Francis Crick Institute, London NW1 1AT, United Kingdom.
3
Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
4
Department of Microbiology and Immunology, Columbia University Irving Medical Center, New York, New York 10032, USA.
5
Department of Genetics and Development, Columbia University Irving Medical Center, New York, New York 10032, USA.
6
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

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.

KEYWORDS:

DNA repair; Dmc1; Rad51; homologous recombination; meiosis

PMID:
31371435
DOI:
10.1101/gad.328062.119

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center