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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1191-1207
Number of pages17
JournalGenes and Development
Volume33
Issue number17-18
DOIs
StatePublished - Sep 1 2019

Keywords

  • DNA repair
  • Dmc1
  • Homologous recombination
  • Meiosis
  • Rad51]

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint Dive into the research topics of 'Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination'. Together they form a unique fingerprint.

Cite this