DNA damaging agents trigger the expression of the HML silent mating type locus in Saccharomyces cerevisiae

Mutat Res Genet Toxicol Environ Mutagen. 2018 Nov:835:16-20. doi: 10.1016/j.mrgentox.2018.08.007. Epub 2018 Aug 24.

Abstract

Many DNA damaging agents also react with RNA and protein, and could thus cause epigenetic as well as genotoxic changes. To investigate which DNA damaging agents alter epigenetic states, we studied the chemical-induced changes in expression of the yeast silent mating type locus HMLα, which can be triggered by inhibiting yeast Sir2. We observed that the alkylating agent methyl methane sulfonate (MMS) can result in HMLα expression, using a colony sector assay that results from expression of a HML-positioned cre gene. Using single-cell imaging we also observed that alkylating agents, including MMS and methyl-3-nitro-1-nitrosoguanidine (MNNG), as well as short-wave UV, also decreased HML silencing. We suggest that chemical-induced alterations in heterochromatin structure could confer transient phenotypic changes that affect the cellular responses to DNA damaging agents.

Keywords: Budding yeast; DNA damaging agent; Epigenetics; Sir-mediated gene silencing.

MeSH terms

  • DNA, Fungal / genetics*
  • Gene Expression Regulation, Fungal / drug effects*
  • Gene Silencing*
  • Genes, Mating Type, Fungal*
  • Heterochromatin / drug effects
  • Heterochromatin / genetics
  • Heterochromatin / pathology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Sulfinic Acids / pharmacology*

Substances

  • DNA, Fungal
  • Heterochromatin
  • Saccharomyces cerevisiae Proteins
  • Sulfinic Acids
  • methyl methanethiosulfinate