Base excision repair activities required for yeast to attain a full chronological life span

Aging Cell. 2003 Apr;2(2):93-104. doi: 10.1046/j.1474-9728.2003.00041.x.

Abstract

The chronological life span of yeast, the survival of stationary (G0) cells over time, provides a model for investigating certain of the factors that may influence the aging of non-dividing cells and tissues in higher organisms. This study measured the effects of defined defects in the base excision repair (BER) system for DNA repair on this life span. Stationary yeast survives longer when it is pre-grown on respiratory, as compared to fermentative (glucose), media. It is also less susceptible to viability loss as the result of defects in DNA glycosylase/AP lyases (Ogg1p, Ntg1p, Ntg2p), apurinic/apyrimidinic (AP) endonucleases (Apn1p, Apn2p) and monofunctional DNA glycosylase (Mag1p). Whereas single BER glycosylase/AP lyase defects exerted little influence over such optimized G0 survival, this survival was severely shortened with the loss of two or more such enzymes. Equally, the apn1delta and apn2delta single gene deletes survived as well as the wild type, whereas a apn1delta apn2delta double mutant totally lacking in any AP endonuclease activity survived poorly. Both this shortened G0 survival and the enhanced mutagenicity of apn1delta apn2delta cells were however rescued by the over-expression of either Apn1p or Apn2p. The results highlight the vital importance of BER in the prevention of mutation accumulation and the attainment of the full yeast chronological life span. They also reveal an appreciable overlap in the G0 maintenance functions of the different BER DNA glycosylases and AP endonucleases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Carbon-Oxygen Lyases / genetics
  • Carbon-Oxygen Lyases / physiology
  • DNA Damage
  • DNA Glycosylases*
  • DNA Repair Enzymes
  • DNA Repair*
  • DNA, Fungal / genetics
  • DNA, Fungal / metabolism
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • DNA-Formamidopyrimidine Glycosylase
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / physiology
  • Fermentation / drug effects
  • Gene Deletion
  • Glucose / pharmacology
  • Glycerol / pharmacology
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / physiology
  • Oxidative Stress
  • Recombinant Fusion Proteins / physiology
  • Resting Phase, Cell Cycle
  • Saccharomyces cerevisiae / cytology*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / physiology*

Substances

  • DNA, Fungal
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Endodeoxyribonucleases
  • Apn1 protein, S cerevisiae
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • MAG1 protein, S cerevisiae
  • DNA-Formamidopyrimidine Glycosylase
  • Carbon-Oxygen Lyases
  • DNA-(Apurinic or Apyrimidinic Site) Lyase
  • NTG1 protein, S cerevisiae
  • NTG2 protein, S cerevisiae
  • DNA Repair Enzymes
  • Glucose
  • Glycerol