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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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
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author Chen, Fangyi
Tang, Qi
Bian, Ke
Humulock, Zachary T.
Yang, Xuedong
Li, Deyu
Jost, Marco
Drennan, Catherine L.
Essigmann, John M.
author2 Massachusetts Institute of Technology. Center for Environmental Health Sciences
author_facet Massachusetts Institute of Technology. Center for Environmental Health Sciences
Chen, Fangyi
Tang, Qi
Bian, Ke
Humulock, Zachary T.
Yang, Xuedong
Li, Deyu
Jost, Marco
Drennan, Catherine L.
Essigmann, John M.
author_sort Chen, Fangyi
collection MIT
description 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).
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spelling mit-1721.1/1163952022-09-23T14:52:46Z Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA Chen, Fangyi Tang, Qi Bian, Ke Humulock, Zachary T. Yang, Xuedong Li, Deyu Jost, Marco Drennan, Catherine L. Essigmann, John M. Massachusetts Institute of Technology. Center for Environmental Health Sciences Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Jost, Marco Drennan, Catherine L. Essigmann, John M 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). 2018-06-19T13:15:21Z 2018-06-19T13:15:21Z 2016-02 2015-12 2018-06-15T17:18:07Z Article http://purl.org/eprint/type/JournalArticle 0893-228X 1520-5010 http://hdl.handle.net/1721.1/116395 Chen, Fangyi et al. “Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA.” Chemical Research in Toxicology 29, 4 (March 2016): 687–693 © 2016 American Chemical Society https://orcid.org/0000-0002-2196-5691 http://dx.doi.org/10.1021/ACS.CHEMRESTOX.5B00522 Chemical Research in Toxicology Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC
spellingShingle Chen, Fangyi
Tang, Qi
Bian, Ke
Humulock, Zachary T.
Yang, Xuedong
Li, Deyu
Jost, Marco
Drennan, Catherine L.
Essigmann, John M.
Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA
title Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA
title_full Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA
title_fullStr Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA
title_full_unstemmed Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA
title_short Adaptive Response Enzyme AlkB Preferentially Repairs 1-Methylguanine and 3-Methylthymine Adducts in Double-Stranded DNA
title_sort adaptive response enzyme alkb preferentially repairs 1 methylguanine and 3 methylthymine adducts in double stranded dna
url http://hdl.handle.net/1721.1/116395
https://orcid.org/0000-0002-2196-5691
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