Alpha-ketoglutarate-dependent dioxygenase alkB homolog 3

Definition:

Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A). Repairs alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation. Has a strong preference for single-stranded DNA. Able to process alkylated m3C within double-stranded regions via its interaction with ASCC3, which promotes DNA unwinding to generate single-stranded substrate needed for ALKBH3. Can repair exocyclic 3,N4-ethenocytosine adducs in single-stranded DNA. Also acts on RNA. Demethylates N(1)-methyladenosine (m1A) RNA, an epigenetic internal modification of messenger RNAs (mRNAs) highly enriched within 5'-untranslated regions (UTRs) and in the vicinity of start codons. Requires molecular oxygen, alpha-ketoglutarate and iron.

References:

[1]. Dan Dominissini, et al. The dynamic N(1)-methyladenosine methylome in eukaryotic messenger RNA. Nature. 2016 Feb 25;530(7591):441-6. [Content Brief]

[2]. Tod Duncan, et al. Reversal of DNA alkylation damage by two human dioxygenases. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16660-5. [Content Brief]

[3]. Yu Zhao, et al. Noncanonical regulation of alkylation damage resistance by the OTUD4 deubiquitinase. EMBO J. 2015 Jun 12;34(12):1687-703. [Content Brief]

[4]. Dong-Hyun Lee, et al. Repair of methylation damage in DNA and RNA by mammalian AlkB homologues. J Biol Chem. 2005 Nov 25;280(47):39448-59. [Content Brief]

[5]. Daria Zdżalik, et al. Differential repair of etheno-DNA adducts by bacterial and human AlkB proteins. DNA Repair (Amst). 2015 Jun;30:1-10. [Content Brief]

[6]. Xiaoyu Li, et al. Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome. Nat Chem Biol. 2016 May;12(5):311-6. [Content Brief]

[7]. Per Arne Aas, et al. Human and bacterial oxidative demethylases repair alkylation damage in both RNA and DNA. Nature. 2003 Feb 20;421(6925):859-63. [Content Brief]

[8]. Ottar Sundheim, et al. Human ABH3 structure and key residues for oxidative demethylation to reverse DNA/RNA damage. EMBO J. 2006 Jul 26;25(14):3389-97. [Content Brief]

[9]. Baoen Chen, et al. Mechanistic insight into the recognition of single-stranded and double-stranded DNA substrates by ABH2 and ABH3. Mol Biosyst. 2010 Nov;6(11):2143-9. [Content Brief]

[10]. Sebastian Dango, et al. DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. Mol Cell. 2011 Nov 4;44(3):373-84. [Content Brief]

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