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PDBsum entry 2ge2
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References listed in PDB file
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Key reference
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Title
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Structure and stability of duplex DNA containing the 3-(Deoxyguanosin-N2-Yl)-2-Acetylaminofluorene (dg(n2)-Aaf) lesion: a bulky adduct that persists in cellular DNA.
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Authors
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T.Zaliznyak,
R.Bonala,
F.Johnson,
C.De los santos.
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Ref.
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Chem Res Toxicol, 2006,
19,
745-752.
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PubMed id
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Abstract
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The carcinogenic environmental pollutant 2-nitrofluorene produces several DNA
adducts including the minor 3-(deoxyguanosin-N(2)-yl)-2-acetylaminofluorene
(dG(N(2))-AAF) lesion, which persists for long times in rat tissue DNA after
discontinuation of carcinogen administration. Here, we present the solution
structure of a dG(N(2))-AAF duplex as determined by NMR spectroscopy and
restrained molecular dynamics. The data establish a regular right-handed
conformation with Watson-Crick base pair alignments throughout the duplex. The
AAF moiety resides in the minor grove of the helix with its long axis directed
toward the 5'-end of the modified strand. Restrained molecular dynamics shows
that the duplex structure adjusts to the AAF lesion, reducing its exposure to
water molecules. Analysis of UV melting profiles shows that the presence of
dG(N(2))-AAF increases the thermal and thermodynamic stability of duplex DNA, an
effect that is driven by a favorable entropy. The structure and stability of the
dG(N(2))-AAF duplex have important implications in understanding the recognition
of bulky lesions by the DNA repair system.
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Headers
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