title: The AlkB Family of Fe(II)/α-Ketoglutarate-dependent Dioxygenases: Repairing Nucleic Acid Alkylation Damage and Beyond.
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.
authors.affiliation: Departments of Chemistry and Biological Engineering and the Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Fedeles
authors.affiliation: Departments of Chemistry and Biological Engineering and the Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors.forename: Vipender
authors.initials: V
authors.lastname: Singh
authors.affiliation: Departments of Chemistry and Biological Engineering and the Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139.
authors.forename: James C
authors.initials: JC
authors.lastname: Delaney
authors.affiliation: Departments of Chemistry and Biological Engineering and the Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Electronic address: deyuli@uri.edu.
authors.forename: Deyu
authors.initials: D
authors.lastname: Li
authors.affiliation: Departments of Chemistry and Biological Engineering and the Center for Environmental Health Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139. Electronic address: jessig@mit.edu.
authors.forename: John M
authors.initials: JM
authors.lastname: Essigmann
mesh_terms: D000071501:AlkB Homolog 4, Lysine Demethylase; D000478:Alkylation; D004249:DNA Damage; D004260:DNA Repair; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases / Q000235:genetics / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000235:genetics; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism*; D008958:Models, Molecular; D005810:Multigene Family; D010084:Oxidation-Reduction; D013379:Substrate Specificity
chemical_list: D004277:DNA, Single-Stranded; D029968:Escherichia coli Proteins; D007527:Isoenzymes; D007656:Ketoglutaric Acids; D007501:Iron; D006899:Mixed Function Oxygenases; D049308:Dioxygenases; C466427:AlkB protein, E coli; C557720:ALKBH4 protein, human; D000071501:AlkB Homolog 4, Lysine Demethylase
keywords: DNA demethylation; DNA repair; RNA demethylation; RNA repair; alkB; alkylation damage; dioxygenase; direct reversal; metalloprotein; substrate specificity