1ua0

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{{STRUCTURE_1ua0| PDB=1ua0 | SCENE= }}
{{STRUCTURE_1ua0| PDB=1ua0 | SCENE= }}
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'''Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase'''
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===Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase===
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==Overview==
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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.
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(as it appears on PubMed at http://www.pubmed.gov), where 15385534 is the PubMed ID number.
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{{ABSTRACT_PUBMED_15385534}}
==About this Structure==
==About this Structure==
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[[Category: Protein-dna complex]]
[[Category: Protein-dna complex]]
[[Category: Translation replication]]
[[Category: Translation replication]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:57:17 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:19:34 2008''

Revision as of 18:19, 27 July 2008

Image:1ua0.png

Template:STRUCTURE 1ua0

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

Template:ABSTRACT PUBMED 15385534

About this Structure

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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