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 journalArticle

4 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

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  • Cite this

    Steinfeld, J. B., Beláň, O., Kwon, Y., Terakawa, T., Al-Zain, A., Smith, M. J., Crickard, J. B., Qi, Z., Zhao, W., Rothstein, R., Symington, L. S., Sung, P., Boulton, S. J., & Greene, E. C. (2019). Defining the influence of Rad51 and Dmc1 lineage-specific amino acids on genetic recombination. Genes and Development, 33(17-18), 1191-1207. https://doi.org/10.1101/gad.328062.119