1ua0

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spinqualitylabelsall models 1ua0, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase

Overview

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.

About this Structure

1UA0 is a Protein complex structure of sequences from Geobacillus stearothermophilus with SUC, SO4 and AF as ligands. Active as DNA-directed DNA polymerase, with EC number 2.7.7.7 Full crystallographic information is available from OCA.

Reference

Observing translesion synthesis of an aromatic amine DNA adduct by a high-fidelity DNA polymerase., Hsu GW, Kiefer JR, Burnouf D, Becherel OJ, Fuchs RP, Beese LS, J Biol Chem. 2004 Nov 26;279(48):50280-5. Epub 2004 Sep 22. PMID:15385534

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