Open AccessBase excision repair activities required for yeast to attain a full chronological life span
Author(s) -
Maclean Morag J.,
Aamodt Randi,
Harris Nicholas,
Alseth Ingrun,
Seeberg Erling,
Bjørås Magnar,
Piper Peter W.
Publication year - 2003
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1046/j.1474-9728.2003.00041.x
Subject(s) - base excision repair , dna glycosylase , ap site , ap endonuclease , biology , dna repair , dna (apurinic or apyrimidinic site) lyase , endonuclease , yeast , mutant , dna damage , dna , genetics , gene , microbiology and biotechnology , biochemistry
Summary The chronological life span of yeast, the survival of stationary (G 0 ) 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 pregrown 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 G 0 survival, this survival was severely shortened with the loss of two or more such enzymes. Equally, the apn1 Δ and apn2 Δ single gene deletes survived as well as the wild type, whereas a apn1 Δ apn2 Δ double mutant totally lacking in any AP endonuclease activity survived poorly. Both this shortened G 0 survival and the enhanced mutagenicity of apn1 Δ apn2 Δ cells were however rescued by the overexpression 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 G 0 maintenance functions of the different BER DNA glycosylases and AP endonucleases.