@article{dc8305228f304c999f455a131301b2c6,
title = "Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination",
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, Homologous recombination, Meiosis, Rad51]",
author = "Steinfeld, {Justin B.} and Ondrej Bel{\'a}{\v n} and Youngho Kwon and Tsuyoshi Terakawa and Amr Al-Zain and Smith, {Michael J.} and Crickard, {J. Brooks} and Zhi Qi and Weixing Zhao and Rodney Rothstein and Symington, {Lorraine S.} and Patrick Sung and Boulton, {Simon J.} and Greene, {Eric C.}",
note = "Funding Information: We are grateful to members of the Greene, Boulton, Rothstein, Symington, and Sung laboratories for helpful conversations. We thank Daniel Duzdevich for discussion and experimental assistance, and Johannes Stigler for assistance with data analysis. This work was supported in part by National Institutes of Health (NIH) training grants F31CA210663 (to J.B.S.) and T32GM007088 (to M.J.S.); NIH grants R35GM118026 (to E.C.G.), R35GM126997 (to L.S.S.), R35GM118180 (to R.R.), R01ES007061 (to P.S.), and P01CA92584 (to P.S. and E.C.G); and National Science Foundation grant MCB-1154511 (to E.C.G.). J.B.C. is the Mark Foundation for Cancer Research Fellow for the Damon-Runyon Cancer Research Foundation (DRG 2310-17). The Boulton laboratory is supported by the Francis Crick Institute, which receives its core funding from Cancer Research UK (FC0010048), the UK Medical Research Council (FC0010048), and the Wellcome Trust (FC0010048). S.J.B. is also the recipient of a European Research Council (ERC) Advanced Investigator Grant (TelMetab) and Wellcome Trust Senior Investigator and Collaborative Grant (to S.J.B and E.C.G.).",
year = "2019",
month = sep,
day = "1",
doi = "10.1101/gad.328062.119",
language = "English (US)",
volume = "33",
pages = "1191--1207",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "17-18",
}