Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase

Hsu, Gerald W., Kiefer, James R., Burnouf, Dominique, Becherel, Olivier J., Fuchs, Robert P. P. and Beese, Lorena S. (2004) Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase. Journal of Biological Chemistry, 279 48: 50280-50285. doi:10.1074/jbc.M409224200

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Author Hsu, Gerald W.
Kiefer, James R.
Burnouf, Dominique
Becherel, Olivier J.
Fuchs, Robert P. P.
Beese, Lorena S.
Title Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
1083-351X
Publication date 2004-11-26
Sub-type Article (original research)
DOI 10.1074/jbc.M409224200
Open Access Status File (Publisher version)
Volume 279
Issue 48
Start page 50280
End page 50285
Total pages 6
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
Aromatic amines have been studied for more than a half-century as model carcinogens representing a class of chemicals that form bulky adducts to the C8 position of guanine in DNA. Among these guanine adducts, the N-(2′-deoxyguanosin-8-yl)-aminofluorene (G-AF) and N-2-(2′- deoxyguanosin-8-yl)-acetylaminofluorene (G-AAF) derivatives are the best studied. Although G-AF and G-AAF differ by only an acetyl group, they exert different effects on DNA replication by replicative and high-fidelity DNA polymerases. Translesion synthesis of G-AF is achieved with high-fidelity polymerases, whereas replication of G-AAF requires specialized bypass polymerases. Here we have presented structures of G-AF as it undergoes one round of accurate replication by a high-fidelity DNA polymerase. Nucleotide incorporation opposite G-AF is achieved in solution and in the crystal, revealing how the polymerase accommodates and replicates past G-AF, but not G-AAF. Like an unmodified guanine, G-AF adopts a conformation that allows it to form Watson-Crick hydrogen bonds with an opposing cytosine that results in protrusion of the bulky fluorene moiety into the major groove. Although incorporation opposite G-AF is observed, the C:G-AF base pair induces distortions to the polymerase active site that slow translesion synthesis.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
 
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Created: Tue, 09 Aug 2016, 16:20:36 EST by Olivier Becherel on behalf of Learning and Research Services (UQ Library)