Molecular modeling studies of a deoxyoctanucleotide containing a dihydrouridine lesion

Conference · Sat Dec 31 00:00:00 EST 1994

OSTI ID:134859

Cooney, M G; Doetsch, P W ^[1]

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1. Emory Univ. School of Medicine, Atlanta, GA (United States)

Oxidative and radiation-induced DNA damages lead to diverse structural alterations in the DNA such as base modifications, strand breaks, and abasic (AP) sites. Examples of base damages are pyrimidines with saturated, cleaved, or contracted rings; pyrimidine dimers; and oxidized purines. Since unrepaired DNA damage can result in mutations, neoplastic transformation, or cell death, DNA repair is an essential survival mechanism for all known living organisms. Structural recognition of damaged DNA by repair enzymes is central to the repair process, and thus an important goal in DNA repair research is a greater understanding of structural modifications in the helix arising from base modifications. Computer simulation and 2-D NMR methods have been successfully combined to yield considerable information on structural details such as torsion angles, sugar puckers, and interbase hydrogen bonding for 9-base pair duplexes with intrahelical AP sites, a hexamer with an extrahelical AP site, and an oligo with a bulged dG residue. We have therefore undertaken structural studies of short synthetic deoxyoligonucleotides, each containing a single modified base. Molecular modeling in the absence of NMR data provides an initial wide range of configurations of low potential energy; subsequently, nuclear Overhauser enhancement spectroscopy (NOESY) gives ranges for interproton distances and some backbone and sugar pucker torsion angles, used to refine the computer models.

• Research Organization: New York Academy of Sciences, New York, NY (United States)
• OSTI ID: 134859
• Report Number(s): CONF-9307221-; TRN: 95:007741-0026
• Resource Relation: Conference: DNA damage: effects on DNA structure and protein recognition, Burlington, VT (United States), 31 Jul - 4 Aug 1993; Other Information: PBD: 1994; Related Information: Is Part Of DNA damage: Effects on DNA structure and protein recognition; Wallace, S.S.; Van Houten, B.; Kow, Yoke Wah [eds.]; PB: 395 p.
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 MATHEMATICS
COMPUTERS
INFORMATION SCIENCE
MANAGEMENT
LAW
MISCELLANEOUS
DNA
MUTATIONS
DNA REPAIR
GENETIC RADIATION EFFECTS
STRAND BREAKS
STRUCTURE-ACTIVITY RELATIONSHIPS
BIOLOGICAL MODELS
COMPUTERIZED SIMULATION
ENZYMES
ENZYME ACTIVITY
PURINES
OXIDATION
ESCHERICHIA COLI
NMR IMAGING
SPECTROSCOPY
URIDINE
DNA HELICASES
PROTEINS
PYRIMIDINE DIMERS
OLIGONUCLEOTIDES