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Publication Abstract from PubMed

N(6)-methyladenosine (6mA) is a DNA modification that has recently been found to play regulatory roles during mammalian early embryo development and mitochondrial transcription. We found that a dioxygenase CcTet from the fungus Coprinopsis cinerea is also a dsDNA 6mA demethylase. It oxidizes 6mA to the intermediate N(6)-hydroxymethyladenosine (6hmA) with robust activity of 6mA-containing duplex DNA (dsDNA) as well as isolated genomics DNA. Structural characterization revealed that CcTet utilizes three flexible loop regions and two key residues-D337 and G331-in the active pocket to preferentially recognize substrates on dsDNA. A CcTet D337F mutant protein retained the catalytic activity on 6mA but lost activity on 5-methylcytosine. Our findings uncovered a 6mA demethylase that works on dsDNA, suggesting potential 6mA demethylation in fungi and elucidating 6mA recognition and the catalytic mechanism of CcTet. The CcTet D337F mutant protein also provides a chemical biology tool for future functional manipulation of DNA 6mA in vivo.

A fungal dioxygenase CcTet serves as a eukaryotic 6mA demethylase on duplex DNA.,Mu Y, Zhang L, Hu J, Zhou J, Lin HW, He C, Chen HZ, Zhang L Nat Chem Biol. 2022 Jun 2. pii: 10.1038/s41589-022-01041-3. doi:, 10.1038/s41589-022-01041-3. PMID:35654845^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.