The pattern of sensitivity of yeast dna2 mutants to DNA damaging agents suggests a role in DSB and postreplication repair pathways

Mutat Res. 2000 Apr 28;459(3):173-86. doi: 10.1016/s0921-8777(99)00072-5.

Abstract

The Saccharomyces cerevisiae DNA2 gene encodes a DNA-stimulated ATPase and DNA helicase/nuclease essential for DNA replication. In characterizing dna2 mutants, we have found that Dna2p also participates in DNA repair or in damage avoidance mechanisms. dna2 mutants are sensitive to X rays, although they are less sensitive than rad52 mutants. The X-ray sensitivity of dna2 mutants is suppressed by overexpression of a 5' to 3' exonuclease, the yeast FEN-1 structure-specific nuclease, encoded by the RAD27 gene, which also suppresses the growth defect of dna2-ts mutants. SGS1 encodes a helicase with similar properties to Dna2 protein. Although sgs1Delta mutants are resistant to X rays, dna2-2 sgs1Delta double mutants are more sensitive to X rays than the dna2-2 mutant. Temperature sensitive dna2 mutants are only slightly sensitive to UV light, show normal levels of spontaneous and UV induced mutagenesis, and have only a 2.5-fold elevated level of dinucleotide tract instability compared to wildtype. However, dna2Delta strains kept alive by overproduction of RAD27 are highly sensitive to UV light. These phenotypes, in addition to the epistasis analysis reported, allow us to propose that Dna2 is involved in postreplication and DSB repair pathways.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Triphosphatases / genetics*
  • Adenosine Triphosphatases / metabolism
  • Cell Cycle / radiation effects
  • Cell Survival / genetics
  • Cell Survival / radiation effects
  • Chromosome Breakage / genetics
  • DNA Helicases / genetics*
  • DNA Helicases / metabolism
  • DNA Repair / genetics*
  • DNA Repair / radiation effects
  • DNA Replication / genetics
  • DNA Replication / radiation effects
  • DNA, Fungal / drug effects
  • DNA, Fungal / metabolism
  • DNA, Fungal / radiation effects
  • Dinucleotide Repeats / genetics
  • Dose-Response Relationship, Radiation
  • Endodeoxyribonucleases / biosynthesis
  • Endodeoxyribonucleases / genetics
  • Flap Endonucleases
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Mutation / radiation effects*
  • RecQ Helicases
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae / radiation effects*
  • Saccharomyces cerevisiae Proteins*
  • Temperature
  • Ultraviolet Rays

Substances

  • DNA, Fungal
  • Fungal Proteins
  • Saccharomyces cerevisiae Proteins
  • Endodeoxyribonucleases
  • Flap Endonucleases
  • RAD27 protein, S cerevisiae
  • Adenosine Triphosphatases
  • SGS1 protein, S cerevisiae
  • DNA Helicases
  • DNA2 protein, S cerevisiae
  • RecQ Helicases