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Vol 55(2021) N 2 p. 195-212; DOI 10.1134/S0026893321020072 Full Text

A.V. Endutkin1*, D.O. Zharkov1,2**

GO System, a DNA Repair Pathway to Cope with Oxidative Damage

1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, Novosibirsk, 630090 Russia
2Novosibirsk State University, Novosibirsk, 630090 Russia

*aend@niboch.nsc.ru
**dzharkov@niboch.nsc.ru
Received - 2020-10-02; Revised - 2020-10-14; Accepted - 2020-10-20

The GO system is part of the DNA base excision repair pathway and is required for the error-free repair of 8-oxoguanine (oxoG), one of the most common oxidative DNA lesions. Due to the ability of oxoG to form oxoG:A mispairs, this base is highly mutagenic. Its repair requires the action of two enzymes: 8-oxoguanine DNA glycosylase (Fpg or MutM in bacteria and OGG1 in eukaryotes), which removes oxoG from oxoG:C pairs, and adenine DNA glycosylase (MutY in bacteria and MUTYH in eukaryotes), which removes A from oxoG:A mispairs to prevent mutations. The third enzyme of the system (MutT in bacteria and MTH1 or NUDT1 in eukaryotes) hydrolyzes 8-oxo-2'-deoxyguanosine triphosphate, thus preventing its incorporation into DNA. Recent data point to the proteins of the GO system as promising targets for the therapy of cancer, autoimmune diseases, and bacterial infections. This review highlights the structure and specificity of the GO system in bacteria and eukaryotes and its unique role in mutation avoidance.

DNA damage, DNA repair, mutagenesis, oxidative stress, 8-oxoguanine, DNA glycosylases, nucleoside triphosphate hydrolases



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