Type of Publication: | Journal article |
Publication status: | Published |
URI (citable link): | http://nbn-resolving.de/urn:nbn:de:bsz:352-0-368262 |
Author: | Wyss, Laura A.; Nilforoushan, Arman; Williams, David M.; Marx, Andreas; Sturla, Shana J. |
Year of publication: | 2016 |
Published in: | Nucleic Acids Research ; 44 (2016), 14. - pp. 6564-6573. - ISSN 0301-5610. - eISSN 1362-4962 |
Pubmed ID: | 27378785 |
DOI (citable link): | https://dx.doi.org/10.1093/nar/gkw589 |
Summary: |
Enzymatic approaches for locating alkylation adducts at single-base resolution in DNA could enable new technologies for understanding carcinogenesis and supporting personalized chemotherapy. Artificial nucleotides that specifically pair with alkylated bases offer a possible strategy for recognition and amplification of adducted DNA, and adduct-templated incorporation of an artificial nucleotide has been demonstrated for a model DNA adduct O6-benzylguanine by a DNA polymerase. In this study, DNA adducts of biological relevance, O6-methylguanine (O6-MeG) and O6-carboxymethylguanine (O6-CMG), were characterized to be effective templates for the incorporation of benzimidazole-derived 2'-deoxynucleoside-5'-O-triphosphates ( BENZI: TP and BIM: TP) by an engineered KlenTaq DNA polymerase. The enzyme catalyzed specific incorporation of the artificial nucleotide BENZI: opposite adducts, with up to 150-fold higher catalytic efficiency for O6-MeG over guanine in the template. Furthermore, addition of artificial nucleotide BENZI: was required for full-length DNA synthesis during bypass of O6-CMG. Selective incorporation of the artificial nucleotide opposite an O6-alkylguanine DNA adduct was verified using a novel 2',3'-dideoxy derivative of BENZI: TP. The strategy was used to recognize adducts in the presence of excess unmodified DNA. The specific processing of BENZI: TP opposite biologically relevant O6-alkylguanine adducts is characterized herein as a basis for potential future DNA adduct sequencing technologies.
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Subject (DDC): | 540 Chemistry |
Link to License: | In Copyright |
Bibliography of Konstanz: | Yes |
WYSS, Laura A., Arman NILFOROUSHAN, David M. WILLIAMS, Andreas MARX, Shana J. STURLA, 2016. The use of an artificial nucleotide for polymerase-based recognition of carcinogenic O6-alkylguanine DNA adducts. In: Nucleic Acids Research. 44(14), pp. 6564-6573. ISSN 0301-5610. eISSN 1362-4962. Available under: doi: 10.1093/nar/gkw589
@article{Wyss2016artif-37294, title={The use of an artificial nucleotide for polymerase-based recognition of carcinogenic O6-alkylguanine DNA adducts}, year={2016}, doi={10.1093/nar/gkw589}, number={14}, volume={44}, issn={0301-5610}, journal={Nucleic Acids Research}, pages={6564--6573}, author={Wyss, Laura A. and Nilforoushan, Arman and Williams, David M. and Marx, Andreas and Sturla, Shana J.} }
Wyss_0-368262.pdf | 172 |