NDLI: Solution structure of a DNA decamer duplex containing the stable 3′ T⋅G base pair of the pyrimidine(6–4)pyrimidone photoproduct [(6–4) adduct]: Implications for the highly specific 3′ T → C transition of the (6–4) adduct

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Solution structure of a DNA decamer duplex containing the stable 3′ T⋅G base pair of the pyrimidine(6–4)pyrimidone photoproduct [(6–4) adduct]: Implications for the highly specific 3′ T → C transition of the (6–4) adduct

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Solution structure of a DNA decamer duplex containing the stable 3′ T⋅G base pair of the pyrimidine(6–4)pyrimidone photoproduct [(6–4) adduct]: Implications for the highly specific 3′ T → C transition of the (6–4) adduct

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Hwang, G. S. Choi, B. S. Lee, J. H.
Description	Author Affiliation: Lee JH ( Department of Chemistry, Korea Advanced Institute of Science and Technology, 373-1, Kusong-dong, Yusong-gu, Taejon 305-701, Korea.);
Abstract	The pyrimidine(6-4)pyrimidone photoproduct [(6-4) adduct] is one of the major photoproducts induced by UV irradiation of DNA and occurs at TpT sites. The (6-4) adduct is highly mutagenic and leads most often to a 3' T --> C transition with 85% replicating error frequency [LeClerc, J. E., Borden, A. & Lawrence, C. W. (1991) Proc. Natl. Acad. Sci. USA 88, 9685-9689]. To determine the origin of the specific 3' T --> C transition of the (6-4) adduct, we have used experimental NMR restraints and molecular dynamics to determine the solution structure of a (6-4)-lesion DNA decamer duplex that contains a mismatched base pair between the 3' T residue and an opposed G residue. Normal Watson-Crick-type hydrogen bonding is retained at the 5' T of the lesion site. The O2 carbonyl of the 3' T residue forms hydrogen bonds with the imino and amino protons of the opposed G residue. This potential hydrogen bonding stabilizes the overall helix and restores the highly distorted conformation of the (6-4) adduct to the typical B-form-like DNA structure. This structural feature can explain the marked preference for the insertion of an A residue opposite the 5' T and a G residue opposite the 3' T of the (6-4) lesion during trans-lesion synthesis. Thus these insertions yield the predominant 3' T --> C transition.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	12
Volume Number	96
Language	English
Publisher	National Academy of Sciences
Publisher Date	1999-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	DNA Chemistry Nucleic Acid Conformation Pyrimidine Dimers Animals Base Pairing Radiation Effects DNA Adducts Hydrogen Ultraviolet Rays Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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