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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MDPI AG
2021-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/19/10540 |
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| author | Nikita A. Kuznetsov Lyubov Yu. Kanazhevskaya Olga S. Fedorova |
| author_facet | Nikita A. Kuznetsov Lyubov Yu. Kanazhevskaya Olga S. Fedorova |
| author_sort | Nikita A. Kuznetsov |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-03-10T06:59:59Z |
| format | Article |
| id | doaj.art-87f8637096034bff91c37a95abab29b3 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:59:59Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-87f8637096034bff91c37a95abab29b32023-11-22T16:11:29ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-09-0122191054010.3390/ijms221910540DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA DioxygenasesNikita A. Kuznetsov0Lyubov Yu. Kanazhevskaya1Olga S. Fedorova2Institute of Chemical Biology and Fundamental Medicine Siberian Branch of Russian Academy of Sciences, 8 Prospekt Ak. Lavrentieva, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine Siberian Branch of Russian Academy of Sciences, 8 Prospekt Ak. Lavrentieva, 630090 Novosibirsk, RussiaInstitute of Chemical Biology and Fundamental Medicine Siberian Branch of Russian Academy of Sciences, 8 Prospekt Ak. Lavrentieva, 630090 Novosibirsk, RussiaSite-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).https://www.mdpi.com/1422-0067/22/19/10540DNA demethylationDNA dioxygenaseoxygen activationcatalytic mechanismdirect repairepigenetics |
| spellingShingle | Nikita A. Kuznetsov Lyubov Yu. Kanazhevskaya Olga S. Fedorova DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases International Journal of Molecular Sciences DNA demethylation DNA dioxygenase oxygen activation catalytic mechanism direct repair epigenetics |
| title | DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases |
| title_full | DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases |
| title_fullStr | DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases |
| title_full_unstemmed | DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases |
| title_short | DNA Demethylation in the Processes of Repair and Epigenetic Regulation Performed by 2-Ketoglutarate-Dependent DNA Dioxygenases |
| title_sort | dna demethylation in the processes of repair and epigenetic regulation performed by 2 ketoglutarate dependent dna dioxygenases |
| topic | DNA demethylation DNA dioxygenase oxygen activation catalytic mechanism direct repair epigenetics |
| url | https://www.mdpi.com/1422-0067/22/19/10540 |
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