title: Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA.
abstract: 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.
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
authors.forename: Fangyi
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
authors.forename: Qi
authors.initials: Q
authors.lastname: Tang
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
authors.forename: Ke
authors.initials: K
authors.lastname: Bian
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
authors.forename: Zachary T
authors.initials: ZT
authors.lastname: Humulock
authors.affiliation: School of Pharmaceutical Science and Technology, Tianjin University , Tianjin 300072, P. R. China.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Yang
authors.forename: Marco
authors.initials: M
authors.lastname: Jost
authors.forename: Catherine L
authors.initials: CL
authors.lastname: Drennan
authors.forename: John M
authors.initials: JM
authors.lastname: Essigmann
authors.affiliation: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island , Kingston, Rhode Island 02881, United States.
authors.forename: Deyu
authors.initials: D
authors.lastname: Li
mesh_terms: D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase / Q000378:metabolism*; D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism*; D004260:DNA Repair; D004926:Escherichia coli / Q000737:chemistry / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D013379:Substrate Specificity; D013941:Thymine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism
chemical_list: D018736:DNA Adducts; D029968:Escherichia coli Proteins; C017515:1-methylguanine; D006147:Guanine; D004247:DNA; D006899:Mixed Function Oxygenases; C486439:ALKBH3 protein, human; D000071500:AlkB Homolog 3, Alpha-Ketoglutarate-Dependent Dioxygenase; C466427:AlkB protein, E coli; C486440:ALKBH2 protein, human; D000071499:AlkB Homolog 2, Alpha-Ketoglutarate-Dependent Dioxygenase; D013941:Thymine; C002347:3-methylthymine