Alkbh6 has no known function or substrate. Alkbh7 localizes to the mitochondria and plays roles in programmed necrosis and fatty acid oxidation its absence yields obese mice.

Alkbh4 functions in actin demethylation and plays a role in cell division. Alkbh8 acts on tRNA by modifying 5-methyluridine in the anticodon wobble position, important in regulating translation. In vivo, Alkbh5 affects mouse fertility while FTO helps determine body mass. Alkbh5 and FTO also act on m 6A, but using mRNA with effects on gene expression. Alkbh3 demethylates these lesions in single-stranded (ss) DNA, but additionally acts on 6-methyladenine (m 6A) in tRNA. Alkbh2 repairs methylated DNA bases in vivo. Mammals possess nine AlkB homologs (Alkbh1 – Alkbh8 and FTO), but their biological functions are diverse (for references to individual proteins see ). This enzyme hydroxylates 1-methyladenine (m 1A) and 3-methylcytosine (m 3C), releasing formaldehyde to restore the native bases.

Two strains of CRISPR/Cas9-created ALKBH1-deficient HEK293 cells showed increases in mtDNA copy number and mitochondrial dysfunction as revealed by growth measurements and citrate synthase activity assays.ĪlkB, an Escherichia coli protein that catalyzes DNA repair, is an Fe(II)/2-oxoglutarate (2OG)-dependent dioxygenase. Localization and subcellular fractionation studies with the endogenous protein in two human cell strains confirm that ALKBH1 is primarily in the mitochondria. In addition, we find that ALKBH1 293 forms a covalent adduct with the 5′ product of the lyase product in a manner analogous to ALKBH1 Ec. We demonstrate that ALKBH1 produced in mammalian cells (ALKBH1 293) is similar to the protein produced in bacteria (ALKBH1 Ec) with regard to its m 6A demethylase and AP lyase activities. The reported cellular roles of this protein reflect the diverse enzymatic activities and include direct DNA repair, tRNA modification, and histone modification.

The human homolog ALKBH1 has been associated with six different enzymatic activities including DNA or tRNA hydroxylation, cleavage at abasic (AP) sites in DNA, as well as demethylation of histones. Alkbh1 is a mammalian homolog of the Escherichia coli DNA repair enzyme AlkB, an Fe(II) and 2-oxoglutarate dependent dioxygenase that removes alkyl lesions from DNA bases.

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