ALKBH3

The Escherichia coli AlkB protein protects against the cytotoxicity of methylating agents by repair of the specific DNA lesions generated in single-stranded DNA. ALKBH2 and ALKBH3 are E. coli AlkB homologs that catalyze the removal of 1-methyladenine and 3-methylcytosine.

Full Name

AlkB Homolog 3, Alpha-Ketoglutaratedependent Dioxygenase

Function

Dioxygenase that mediates demethylation of DNA and RNA containing 1-methyladenosine (m1A) (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410). Repairs alkylated DNA containing 1-methyladenosine (m1A) and 3-methylcytosine (m3C) by oxidative demethylation (PubMed:12486230, PubMed:12594517, PubMed:16174769, PubMed:25944111). Has a strong preference for single-stranded DNA (PubMed:12486230, PubMed:12594517, PubMed:16174769). 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 (PubMed:22055184). Also acts on RNA (PubMed:12594517, PubMed:16174769, PubMed:26863196, PubMed:26863410, PubMed:16858410). Demethylates N1-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 (PubMed:26863196, PubMed:26863410). Requires molecular oxygen, alpha-ketoglutarate and iron (PubMed:22055184, PubMed:16858410).

Biological Process

Cell population proliferation Source: UniProtKB
DNA dealkylation involved in DNA repair Source: UniProtKB
DNA repair Source: UniProtKB
Oxidative single-stranded DNA demethylation Source: UniProtKB
Oxidative single-stranded RNA demethylation Source: UniProtKB

Cellular Location

Nucleus; Cytoplasm. Colocalizes with ASCC2 and ASCC3 in nuclear foci when cells have been exposed to alkylating agents that cause DNA damage (PubMed:29144457). Predominantly localizes to the nucleus.

PTM

Ubiquitinated; undergoes 'Lys-48'-linked polyubiquitination. OTUD4 promotes USP7 and USP9X-dependent deubiquitination of 'Lys-48'-polyubiquitinated ALKBH3 promoting the repair of alkylated DNA lesions.