DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases

Site-specific DNA methylation plays an important role in epigenetic regulation of gene expression. Chemical methylation of DNA, including the formation of various methylated nitrogenous bases, leads to the formation of genotoxic modifications that impair DNA functions. Despite the fact that differen...

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Bibliographic Details
Published in:International journal of molecular sciences 2021-10, Vol.22 (19), p.10540
Main Authors: Kuznetsov, Nikita A., Kanazhevskaya, Lyubov Yu, Fedorova, Olga S.
Format: Article
Language:English
Subjects:
Adducts
Alkylation
Bases (nucleic acids)
catalytic mechanism
Decomposition
Demethylation
Deoxyribonucleic acid
direct repair
DNA
DNA adducts
DNA damage
DNA demethylation
DNA dioxygenase
DNA methylation
DNA repair
Enzymes
Epigenetics
Gene expression
Genotoxicity
Iron
Ketoglutaric acid
Mammals
Nucleic acids
Oxidation
oxygen activation
Proteins
Repair
Review
Stem cells
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Summary:Site-specific DNA methylation plays an important role in epigenetic regulation of gene expression. Chemical methylation of DNA, including the formation of various methylated nitrogenous bases, leads to the formation of genotoxic modifications that impair DNA functions. Despite the fact that different pathways give rise to methyl groups in DNA, the main pathway for their removal is oxidative demethylation, which is catalyzed by nonheme Fe(II)/α-ketoglutarate–dependent DNA dioxygenases. DNA dioxygenases share a common catalytic mechanism of the oxidation of the alkyl groups on nitrogenous bases in nucleic acids. This review presents generalized data on the catalytic mechanism of action of DNA dioxygenases and on the participation of typical representatives of this superfamily, such as prokaryotic enzyme AlkB and eukaryotic enzymes ALKBH1–8 and TET1–3, in both processes of direct repair of alkylated DNA adducts and in the removal of an epigenetic mark (5-methylcytosine).
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms221910540