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'''Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase''' | '''Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase''' | ||
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==About this Structure== | ==About this Structure== | ||
Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UA0 OCA]. | |||
==Reference== | ==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:[http://www.ncbi.nlm.nih.gov/pubmed/15385534 15385534] | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15385534 15385534] | ||
[[Category: DNA-directed DNA polymerase]] | [[Category: DNA-directed DNA polymerase]] | ||
[[Category: Becherel, O J.]] | [[Category: Becherel, O J.]] | ||
[[Category: Beese, L S.]] | [[Category: Beese, L S.]] | ||
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[[Category: Hsu, G W.]] | [[Category: Hsu, G W.]] | ||
[[Category: Kiefer, J R.]] | [[Category: Kiefer, J R.]] | ||
[[Category: | [[Category: Aminofluorene]] | ||
[[Category: | [[Category: Aromatic amine]] | ||
[[Category: | [[Category: Dna lesion]] | ||
[[Category: | [[Category: Dna polymerase i]] | ||
[[Category: | [[Category: Dna replication]] | ||
[[Category: | [[Category: Klenow fragment]] | ||
[[Category: | [[Category: Protein-dna complex]] | ||
[[Category: | [[Category: Translation replication]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 10:57:17 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 10:57, 3 May 2008
Aminofluorene DNA adduct at the pre-insertion site of a DNA polymerase
OverviewOverview
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 StructureAbout this Structure
Full crystallographic information is available from OCA.
ReferenceReference
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 Page seeded by OCA on Sat May 3 10:57:17 2008