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

• Main Authors: Chen, Fangyi (Author), Tang, Qi (Author), Bian, Ke (Author), Humulock, Zachary T. (Author), Yang, Xuedong (Author), Li, Deyu (Author), Jost, Marco (Contributor), Drennan, Catherine L. (Contributor), Essigmann, John M. (Author)
• Other Authors: Massachusetts Institute of Technology. Center for Environmental Health Sciences (Contributor), Massachusetts Institute of Technology. Department of Biological Engineering (Contributor), Massachusetts Institute of Technology. Department of Biology (Contributor), Massachusetts Institute of Technology. Department of Chemistry (Contributor), Essigmann, John M (Contributor)
• Format: Article
• Language: English
• Published: American Chemical Society (ACS), 2018-06-19T13:15:21Z.
• Subjects: Article
• Online Access: Get fulltext

 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).