DLH1, the Candida albicans homologue of the meiosis-specific DMC1, is not involved in DNA repair but catalyses spontaneous interhomologue recombination and might promote non-crossover events

Cell Microbiol. 2020 Jan;22(1):e13137. doi: 10.1111/cmi.13137. Epub 2019 Nov 11.

Abstract

DLH1, the Candida albicans orthologue of the meiosis-specific recombinase DMC1 was expressed during the mitotic cycle. In contrast to rad51-ΔΔ that displayed reduced growth rate and severe susceptibility to DNA-damaging agents, dlh1-ΔΔ behaved as wild type (WT), rad51-ΔΔ being was epistatic to dlh1-ΔΔ. However, dlh1-ΔΔ showed an increased frequency of spontaneous loss-of-heterozygosity (LOH) at the HIS4/his4 (Chr4) locus. For both WT and dlh1-ΔΔ, His auxotrophs arose via Chr4 loss and interhomologue recombination whereas rad51-ΔΔ and rad51-ΔΔ dlh1-ΔΔ His segregants were formed mainly by chromosome loss and truncation. A few rad51-ΔΔ, but not rad51-ΔΔ dlh1-ΔΔ, segregants showed interhomologue recombination. LOH events at the GAL1/URA3 locus (Chr1; URA3 substitutes one GAL1 allele) in WT and dlh1-ΔΔ involved mainly long tracts of DNA. A few short-tract LOH events were detected in WT but not in dlh1-ΔΔ, and this dlh1-ΔΔ phenotype was partially complemented by a WT DLH1 allele. Long-tract LOH events were also predominant in rad51-ΔΔ, but about half of them arose via chromosome truncation. We suggest that Dlh1, which conserves the Dmc1 lineage-specific amino acid residues, can promote strand invasion and might regulate in combination with Rad51 the length of the conversion tracts and the relative frequencies of mitotic non-crossovers in C. albicans.

Keywords: Candida albicans; DLH1/DMC1; RAD51; crossovers/non-crossovers/chromosome truncation; loss-of-heterozygosity.

MeSH terms

  • Biocatalysis
  • Candida albicans / genetics*
  • Candida albicans / physiology
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • DNA Repair*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Fungal Proteins / genetics*
  • Fungal Proteins / metabolism
  • Meiosis / genetics
  • Mitosis / genetics
  • Recombination, Genetic*

Substances

  • Cell Cycle Proteins
  • DLH1 protein, Candida albicans
  • DNA-Binding Proteins
  • Fungal Proteins