Mutagenic effects of abasic and oxidized abasic lesions in Saccharomyces cerevisiae.
2-deoxyribonolactone (L) and 2-deoxyribose (AP) are abasic sites that are produced by ionizing radiation, reactive oxygen species and a variety of DNA damaging agents. The biological processing of the AP site has been examined in the yeast Saccharomyces cerevisiae. However, nothing is known about how L is processed in this organism. We determined the bypass and mutagenic specificity of DNA containing an abasic site (AP and L) or the AP analog tetrahydrofuran (F) using an oligonucleotide transformation assay. The tetrahydrofuran analog and L were bypassed at 10-fold higher frequencies than the AP lesions. Bypass frequencies of lesions were greatly reduced in the absence of Rev1 or Polzeta (rev3 mutant), but were only marginally reduced in the absence of Poleta (rad30 mutant). Deoxycytidine was the preferred nucleotide inserted opposite an AP site whereas dA and dC were inserted at equal frequencies opposite F and L sites. In the rev1 and rev3 strains, dA was the predominant nucleotide inserted opposite these lesions. Overall, we conclude that both Rev1 and Polzeta are required for the efficient bypass of abasic sites in yeast.
Kow
Yoke W
YW
Department of Radiation Oncology, Emory University School of Medicine, 1365-B Clifton Road NE, Suite B5119, Atlanta, GA 30322, USA. ykow@emory.edu
Bao
Gaobin
G
Minesinger
Brenda
B
Jinks-Robertson
Sue
S
Siede
Wolfram
W
Jiang
Yu Lin
YL
Greenberg
Marc M
MM
D000483:Alleles; D004249:DNA Damage; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D016368:Frameshift Mutation; D005663:Furans / Q000737:chemistry; D016296:Mutagenesis; D009713:Nucleotidyltransferases / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D018384:Oxidative Stress; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D013400:Sugar Acids / Q000737:chemistry; D014170:Transformation, Genetic; D000099270:Y-Family DNA Polymerases
D004259:DNA-Directed DNA Polymerase; D005663:Furans; D009713:Nucleotidyltransferases; D009841:Oligonucleotides; D029701:Saccharomyces cerevisiae Proteins; D013400:Sugar Acids; C056405:2,4,5-trihydroxypentanoic acid gamma-lactone; C018674:tetrahydrofuran; C425929:DNA polymerase zeta; C100951:REV1 protein, S cerevisiae; D000099270:Y-Family DNA Polymerases