Solution structure of a DNA decanter duplex containing the stable 3 T center dot 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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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 C 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.
Publisher
NATL ACAD SCIENCES
Issue Date
1999-06
Language
English
Article Type
Article
Keywords

RELAXATION MATRIX REFINEMENT; THYMINE CYCLOBUTANE DIMER; ESCHERICHIA-COLI; CIS-SYN; DAMAGE RECOGNITION; EXCISION-REPAIR; MAMMALIAN-CELLS; DECAMER DUPLEX; SKIN-CANCER; THYMIDYLYL(3' -> 5' )THYMIDINE

Citation

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.96, no.12, pp.6632 - 6636

ISSN
0027-8424
URI
http://hdl.handle.net/10203/75404
Appears in Collection
CH-Journal Papers(저널논문)
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