Doetsch P W, Morey N J, Swanson R L, Jinks-Robertson S
Departments of Biochemistry and Radiation Oncology, Emory University, Atlanta, Georgia 30322, USA.
Prog Nucleic Acid Res Mol Biol. 2001;68:29-39. doi: 10.1016/s0079-6603(01)68087-5.
The removal of oxidative base damage from the genome of Saccharomyces cerevisiae is thought to occur primarily via the base excision repair (BER) pathway in a process initiated by several DNA N-glycosylase/AP lyases. We have found that yeast strains containing simultaneous multiple disruptions of BER genes are not hypersensitive to killing by oxidizing agents, but exhibit a spontaneous hyperrecombinogenic (hyper-rec) and mutator phenotype. The hyper-rec and mutator phenotypes are further enhanced by elimination of the nucleotide excision repair (NER) pathway. Furthermore, elimination of either the lesion bypass (REV3-dependent) or recombination (RAD52-dependent) pathway results in a further, specific enhancement of the hyper-rec or mutator phenotypes, respectively. Sensitivity (cell killing) to oxidizing agents is not observed unless multiple pathways are eliminated simultaneously. These data suggest that the BER, NER, recombination, and lesion bypass pathways have overlapping specificities in the removal of, or tolerance to, exogenous or spontaneous oxidative DNA damage in S. cerevisiae. Our results also suggest a physiological role for the AP lyase activity of certain BER N-glycosylases in vivo.
酿酒酵母基因组中氧化碱基损伤的去除被认为主要通过碱基切除修复（BER）途径进行，该过程由几种DNA N-糖基化酶/AP裂解酶启动。我们发现，同时含有多个BER基因破坏的酵母菌株对氧化剂杀伤并不敏感，但表现出自发性高重组（hyper-rec）和突变体表型。通过消除核苷酸切除修复（NER）途径，高重组和突变体表型会进一步增强。此外，消除损伤旁路（REV3依赖性）或重组（RAD52依赖性）途径分别导致高重组或突变体表型的进一步特异性增强。除非同时消除多个途径，否则不会观察到对氧化剂的敏感性（细胞杀伤）。这些数据表明，BER、NER、重组和损伤旁路途径在酿酒酵母中外源或自发氧化DNA损伤的去除或耐受性方面具有重叠的特异性。我们的结果还表明某些BER N-糖基化酶的AP裂解酶活性在体内具有生理作用。
