The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond

J Biol Chem. 2015 Aug 21;290(34):20734-20742. doi: 10.1074/jbc.R115.656462. Epub 2015 Jul 7.

Abstract

The AlkB family of Fe(II)- and α-ketoglutarate-dependent dioxygenases is a class of ubiquitous direct reversal DNA repair enzymes that remove alkyl adducts from nucleobases by oxidative dealkylation. The prototypical and homonymous family member is an Escherichia coli "adaptive response" protein that protects the bacterial genome against alkylation damage. AlkB has a wide variety of substrates, including monoalkyl and exocyclic bridged adducts. Nine mammalian AlkB homologs exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes. This minireview presents an overview of the AlkB proteins including recent data on homologs, structural features, substrate specificities, and experimental strategies for studying DNA repair by AlkB family proteins.

Keywords: DNA demethylation; DNA repair; RNA demethylation; RNA repair; alkB; alkylation damage; dioxygenase; direct reversal; metalloprotein; substrate specificity.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • AlkB Homolog 4, Lysine Demethylase
  • Alkylation
  • DNA Damage
  • DNA Repair*
  • DNA, Single-Stranded / genetics
  • DNA, Single-Stranded / metabolism
  • Dioxygenases / genetics
  • Dioxygenases / metabolism*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism*
  • Gene Expression
  • Humans
  • Iron / metabolism*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism
  • Ketoglutaric Acids / metabolism*
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / metabolism*
  • Models, Molecular
  • Multigene Family
  • Oxidation-Reduction
  • Substrate Specificity

Substances

  • DNA, Single-Stranded
  • Escherichia coli Proteins
  • Isoenzymes
  • Ketoglutaric Acids
  • Iron
  • Mixed Function Oxygenases
  • Dioxygenases
  • AlkB protein, E coli
  • ALKBH4 protein, human
  • AlkB Homolog 4, Lysine Demethylase

Associated data

  • PDB/3O1P