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National Institute of Environmental Health Sciences

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Publication Detail

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

Authors: Steinfeld, Justin B; Beláň, Ondrej; Kwon, Youngho; Terakawa, Tsuyoshi; Al-Zain, Amr; Smith, Michael J; Crickard, J Brooks; Qi, Zhi; Zhao, Weixing; Rothstein, Rodney; Symington, Lorraine S; Sung, Patrick; Boulton, Simon J; Greene, Eric C

Published In Genes Dev, (2019 Sep 01)

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.

PubMed ID: 31371435 Exiting the NIEHS site

MeSH Terms: Amino Acids/genetics; Amino Acids/metabolism*; Animals; Base Pair Mismatch; Caenorhabditis elegans Proteins/chemistry; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/metabolism; Caenorhabditis elegans/enzymology; Caenorhabditis elegans/genetics; Conserved Sequence; Mutation; Rad51 Recombinase/chemistry*; Rad51 Recombinase/genetics; Rad51 Recombinase/metabolism*; Recombinant Fusion Proteins/genetics; Recombinant Fusion Proteins/metabolism; Recombinases/chemistry*; Recombinases/genetics; Recombinases/metabolism*; Recombination, Genetic/genetics*; Saccharomyces cerevisiae Proteins/genetics; Saccharomyces cerevisiae Proteins/metabolism; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae/metabolism

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