Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA

The AlkB protein is a repair enzyme that uses an α-ketoglutarate/Fe(II)-dependent mechanism to repair alkyl DNA adducts. AlkB has been reported to repair highly susceptible substrates, such as 1-methyladenine and 3-methylcytosine, more efficiently in ss-DNA than in ds-DNA. Here, we tested the repair...

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Bibliographic Details
Main Authors: Chen, Fangyi, Tang, Qi, Bian, Ke, Humulock, Zachary T., Yang, Xuedong, Li, Deyu, Jost, Marco, Drennan, Catherine L., Essigmann, John M.
Other Authors: Massachusetts Institute of Technology. Center for Environmental Health Sciences
Format: Article
Published: American Chemical Society (ACS) 2018
Online Access:http://hdl.handle.net/1721.1/116395
https://orcid.org/0000-0002-2196-5691
Description
Summary:The AlkB protein is a repair enzyme that uses an α-ketoglutarate/Fe(II)-dependent mechanism to repair alkyl DNA adducts. AlkB has been reported to repair highly susceptible substrates, such as 1-methyladenine and 3-methylcytosine, more efficiently in ss-DNA than in ds-DNA. Here, we tested the repair of weaker AlkB substrates 1-methylguanine and 3-methylthymine and found that AlkB prefers to repair them in ds-DNA. We also discovered that AlkB and its human homologues, ABH2 and ABH3, are able to repair the aforementioned adducts when the adduct is present in a mismatched base pair. These observations demonstrate the strong adaptability of AlkB toward repairing various adducts in different environments. (Chemical Equation Presented).