Calculated distortions of duplex DNA by a cis, syn cyclobutane thymine dimer are unaffected by a 3' TpA step.

Abstract:

:Molecular dynamics simulations were performed on the duplex DNA dodecamers d(CGCGAA TT CGCG): d(CGCGAATTCGCG) and d(GCACGAA TT AAG): d(CTTAATTCGTGC), where TT denotes a cis, syn cyclobutane thymine dimer. The constant temperature and pressure algorithm of the AMBER 4.1 molecular-modeling package was used with explicit water and counterions, periodic boundary conditions and electrostatic interactions evaluated by the particle-mesh Ewald method. Results were analyzed by the CURVES algorithm and its implementation in DIALS and WINDOWS. Calculated distortions of DNA structure by the thymine dimer were qualitatively and quantitatively similar for the two sequences. Despite the enhanced flexibility of the native TpA dinucleotide step, major deviations from the B-DNA values of helicoidal parameters were found only at the Ap and p dinucleotide steps in both sequences. Only the AT base pairs of the two sequences that contain the 5' thymine of the dimers exhibited weakened Watson-Crick hydrogen bonds and anomalous stretching. Hence, we conclude that the pattern of structural perturbations responsible for recognition of cis, syn thymine dimers by repair enzymes is not sensitive to their sequence context.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Cooney MG,Miller JH

doi

10.1093/nar/25.7.1432

subject

Has Abstract

pub_date

1997-04-01 00:00:00

pages

1432-6

issue

7

eissn

0305-1048

issn

1362-4962

pii

gka235

journal_volume

25

pub_type

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