Modeling and molecular mechanical studies of the cis-thymine glycol radiation damage lesion in DNA

Journal Article · Tue Aug 25 04:00:00 EDT 1987 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00391a028· OSTI ID:5871731

Clark, J M; Pattabiraman, N; Jarvis, W; Beardsley, G P

Computer graphics and energy minimization techniques were used to construct a model of DNA containing cis-thymine glycol, an oxidation product of thymine formed in DNA by ionizing radiation. The model simulated an experimental DNA substrate used to study the effects of this lesion on DNA synthesis in vitro. The results derived from the model indicate that cis-thymine glycol lesions introduce localized perturbations of DNA structure. Specifically the model shows that interactions with the neighboring base pair on the 5' side are significantly destabilized by thymine glycol whereas interactions with the 3' base pair are stabilized by the lesion. The magnitude of these effects is modulated by the nucleotide sequence around the lesion, particularly by the nature of the base on the 3' side. The base pair formed between adenine and thymine glycol is energetically stable and shows minimal distortion, suggesting that this lesion retains the ability to direct the insertion of the correct nucleotide during DNA synthesis.

• Research Organization: Yale Univ. School of Medicine, New Haven, CT
• OSTI ID: 5871731
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 26:17; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

560120* -- Radiation Effects on Biochemicals
Cells
& Tissue Culture
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADENINES
ALCOHOLS
AMINES
ANTIMETABOLITES
AROMATICS
AZAARENES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
COMPUTER GRAPHICS
DNA
DRUGS
GLYCOLS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
IONIZING RADIATIONS
MATHEMATICAL MODELS
MOLECULAR MODELS
NUCLEIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PURINES
PYRIMIDINE DIMERS
PYRIMIDINES
RADIATION EFFECTS
RADIATIONS
THYMINE
URACILS