Oxidative demethylase ALKBH5 repairs DNA alkylation damage and protects against alkylation-induced toxicity

Akula, Deepa and O’Connor, Timothy R. and Anindya, Roy (2021) Oxidative demethylase ALKBH5 repairs DNA alkylation damage and protects against alkylation-induced toxicity. Biochemical and Biophysical Research Communications, 534. pp. 114-120. ISSN 0006291X

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Abstract

DNA integrity is challenged by both exogenous and endogenous alkylating agents. DNA repair proteins such as Escherichia coli AlkB family of enzymes can repair 1-methyladenine and 3-methylcytosine adducts by oxidative demethylation. Human AlkB homologue 5 (ALKBH5) is RNA N6-methyladenine demethylase and not known to be involved in DNA repair. Herein we show that ALKBH5 also has weak DNA repair activity and it can demethylate DNA 3-methylcytosine. The mutation of the amino acid residues involved in demethylation also abolishes the DNA repair activity of ALKBH5. Overexpression of ALKBH5 decreases the 3-methylcytosine level in genomic DNA and reduces the cytotoxic effects of the DNA damaging alkylating agent methyl methanesulfonate. Thus, demethylation by ALKBH5 might play a supporting role in maintaining genome integrity.

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