Novel pof1 mutation suppresses the sensitivity to DNA replication inhibitor in fission yeast RecQ helicase mutant

Biochem Biophys Res Commun. 2024 Dec 31:741:151014. doi: 10.1016/j.bbrc.2024.151014. Epub 2024 Nov 20.

Abstract

Homologous recombination is vital for DNA double-strand break repair. Dysfunction in homologous recombination can lead to cell death, mutations, and cancer. In fission yeast (Schizosaccharomyces pombe), RecQ helicase Rqh1 resolves recombination intermediates. We found that rqh1-hd strain impaired growth in media containing hydroxyurea and thiabendazole. Using this condition, we identified a novel pof1 mutation (pof1-A81T) that suppress the poor growth of the rqh1-hd strain on the plate containing hydroxyurea and thiabendazole. Compared to rqh1-hd, rqh1-hd pof1-A81T cells displayed reduced Replication Protein A foci on chromosome bridges after hydroxyurea treatment. This suggests that pof1-A81T mutation suppresses the accumulation of recombination intermediates in hydroxyurea-treated rqh1-hd cells. Additionally, pof1-A81T mutation rescued the segregation defect of nucleolar protein Gar2 observed in hydroxyurea-treated rqh1-hd cells, potentially by mitigating recombination intermediate accumulation in rDNA. These results suggest that the pof1-A81T mutation suppresses the accumulation of recombination intermediates, particularly in rDNA, and alleviates the rqh1 deficiency phenotype in S. pombe.

Keywords: BLM helicases; DNA repair; Homologous recombination; Hydroxyurea; Pof1; Rqh1.

MeSH terms

  • DNA Helicases
  • DNA Replication* / drug effects
  • Homologous Recombination / drug effects
  • Hydroxyurea* / pharmacology
  • Mutation*
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • RecQ Helicases* / genetics
  • RecQ Helicases* / metabolism
  • Schizosaccharomyces pombe Proteins* / genetics
  • Schizosaccharomyces pombe Proteins* / metabolism
  • Schizosaccharomyces* / drug effects
  • Schizosaccharomyces* / genetics
  • Thiabendazole / pharmacology

Substances

  • Schizosaccharomyces pombe Proteins
  • Hydroxyurea
  • RecQ Helicases
  • Rqh1 protein, S pombe
  • Thiabendazole
  • Nucleic Acid Synthesis Inhibitors
  • DNA Helicases