Methylglyoxal disturbs DNA repair and glyoxalase I system in Saccharomyces cerevisiae

Toxicol Mech Methods. 2021 Feb;31(2):107-115. doi: 10.1080/15376516.2020.1838019. Epub 2020 Nov 8.

Abstract

Methylglyoxal (MG) is a highly reactive aldehyde able to form covalent adducts with proteins and nucleic acids, disrupting cellular functions. In this study, we performed a screening of Saccharomyces cerevisiae (S. cerevisiae) strains to find out which genes of cells are responsive to MG, emphasizing genes against oxidative stress and DNA repair. Yeast strains were grown in the YPD-Galactose medium containing MG (0.5 to 12 mM). The tolerance to MG was evaluated by determining cellular growth and cell viability. The toxicity of MG was more pronounced in the strains with deletion in genes engaged with DNA repair checkpoint proteins, namely Rad23 and Rad50. MG also impaired the growth and viability of S. cerevisiae mutant strains Glo1 and Gsh1, both components of the glyoxalase I system. Differently, the strains with deletion in genes encoding for antioxidant enzymes were apparently resistant to MG. In summary, our data indicate that DNA repair and MG detoxification pathways are keys in the control of MG toxicity in S. cerevisiae.

Keywords: S. cerevisiae; DNA repair; Methylglyoxal; glyoxalase system; oxidative stress.

MeSH terms

  • DNA Repair
  • DNA-Binding Proteins
  • Lactoylglutathione Lyase* / genetics
  • Lactoylglutathione Lyase* / metabolism
  • Oxidative Stress
  • Pyruvaldehyde / toxicity
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics

Substances

  • DNA-Binding Proteins
  • RAD23 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Pyruvaldehyde
  • Lactoylglutathione Lyase