ALKBH3

ALKBH3, also known as ABH3, is a human enzyme that belongs to the AlkB family of non-heme Fe(II)/α-ketoglutarate-dependent dioxygenases. It is encoded by the ALKBH3 gene and is involved in the cellular response to alkylation damage to nucleic acids, contributing to the maintenance of genomic and transcript integrity.

Biochemical activity and substrates of ALKBH3 reflect its role in demethylation of alkylated bases. The enzyme catalyzes oxidative demethylation reactions in DNA and RNA substrates, using Fe2+ and α-ketoglutarate as cofactors and molecular oxygen as a reactant. The catalytic cycle converts methylated bases back to their unmodified forms and produces byproducts such as succinate and CO2. ALKBH3 shows a preference for single-stranded nucleic acids and has been described as acting on lesions such as N1-methyladenine and N3-methylcytosine in DNA, with additional evidence for RNA substrates.

Localization and expression of ALKBH3 in human cells indicate that the protein is distributed in both the nucleus and the cytoplasm, with potential involvement in replication and transcription-related processes. Its activity is integrated with other DNA and RNA repair pathways, helping to mitigate the mutagenic effects of alkylating agents.

Clinical relevance and research perspectives have highlighted ALKBH3 in cancer biology. Elevated ALKBH3 expression has been observed in several cancer types and has been linked to cellular resistance to alkylating chemotherapeutic agents, suggesting a role in tumor cell survival under methylation stress. As a result, ALKBH3 is explored as a potential biomarker and therapeutic target, with preclinical studies examining inhibitors or gene-silencing approaches to sensitize tumors to methylating damage.

In summary, ALKBH3 is a human Fe(II)/α-ketoglutarate-dependent dioxygenase that repairs alkylation damage in DNA and RNA, with implications for genome stability and cancer biology.