Enzymology of the repair of free radicals-induced DNA damage

被引:161
作者
Gros, L [1 ]
Saparbaev, MK [1 ]
Laval, J [1 ]
机构
[1] Inst Gustave Roussy, UMR 8532 CNRS, ENS Cachan, LBPA,Grp Reparat ADN, F-94805 Villejuif, France
关键词
oxygen free radicals; oxidative DNA damage; DNA glycosylase; base excision; 8-oxoguanine; AP endonuclease;
D O I
10.1038/sj.onc.1206005
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A number of intrinsic and extrinsic mutagens induce structural damage in cellular DNA. These DNA damages are cytotoxic, miscoding or both and are believed to be at the origin of cell lethality, tissue degeneration, ageing and cancer. In order to counteract immediately the deleterious effects of such lesions, leading to genomic instability, cells have evolved a number of DNA repair mechanisms including the direct reversal of the lesion, sanitation of the dNTPs pools, mismatch repair and several DNA excision pathways including the base excision repair (BER) nucleotide excision repair (NER) and the nucleotide incision repair (NIR). These repair pathways are universally present in living cells and extremely well conserved. This review is focused on the repair of lesions induced by free radicals and ionising radiation. The BER pathway removes most of these DNA lesions, although recently it was shown that other pathways would also be efficient in the removal of oxidised bases. In the BER pathway the process is initiated by a DNA glycosylase excising the modified and mismatched base by hydrolysis of the glycosidic bond between the base and the deoxyribose of the DNA, generating a free base and an abasic site (AP-site) which in turn is repaired since it is cytotoxic and mutagenic.
引用
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页码:8905 / 8925
页数:21
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