Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family

Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage,...

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Main Authors: Anastasiia T. Davletgildeeva, Nikita A. Kuznetsov
Format: Article
Language:English
Published: MDPI AG 2024-09-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/46/9/622
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author Anastasiia T. Davletgildeeva
Nikita A. Kuznetsov
author_facet Anastasiia T. Davletgildeeva
Nikita A. Kuznetsov
author_sort Anastasiia T. Davletgildeeva
collection DOAJ
description Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of <i>Escherichia coli</i> AlkB, nonheme Fe(II)/α-ketoglutarate-dependent dioxygenases ABH1–8, and FTO. Moreover, some of these enzymes have been found to act on several protein targets. In this review, we present up-to-date data on specific features of protein structure, substrate specificity, known roles in the organism, and consequences of disfunction of each of the nine human homologs of AlkB. Special attention is given to reports about the effects of natural single-nucleotide polymorphisms on the activity of these enzymes and to potential consequences for carriers of such natural variants.
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spelling doaj-art-b813c763e808428f9073acdec4f226fe2025-08-20T01:55:22ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452024-09-01469104621049110.3390/cimb46090622Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like FamilyAnastasiia T. Davletgildeeva0Nikita A. Kuznetsov1Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, RussiaInstitute of Chemical Biology and Fundamental Medicine, Siberian Branch of Russian Academy of Sciences, Novosibirsk 630090, RussiaAlkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of <i>Escherichia coli</i> AlkB, nonheme Fe(II)/α-ketoglutarate-dependent dioxygenases ABH1–8, and FTO. Moreover, some of these enzymes have been found to act on several protein targets. In this review, we present up-to-date data on specific features of protein structure, substrate specificity, known roles in the organism, and consequences of disfunction of each of the nine human homologs of AlkB. Special attention is given to reports about the effects of natural single-nucleotide polymorphisms on the activity of these enzymes and to potential consequences for carriers of such natural variants.https://www.mdpi.com/1467-3045/46/9/622macromolecule alkylationdealkylationdioxygenasecatalytic mechanismsingle-nucleotide polymorphismenzyme disfunction
spellingShingle Anastasiia T. Davletgildeeva
Nikita A. Kuznetsov
Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family
Current Issues in Molecular Biology
macromolecule alkylation
dealkylation
dioxygenase
catalytic mechanism
single-nucleotide polymorphism
enzyme disfunction
title Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family
title_full Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family
title_fullStr Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family
title_full_unstemmed Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family
title_short Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family
title_sort dealkylation of macromolecules by eukaryotic α ketoglutarate dependent dioxygenases from the alkb like family
topic macromolecule alkylation
dealkylation
dioxygenase
catalytic mechanism
single-nucleotide polymorphism
enzyme disfunction
url https://www.mdpi.com/1467-3045/46/9/622
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