title: Theoretical and experimental measures of DNA helix stability and their relation to sequence specific repair of O6-ethylguanine lesions.
abstract: Recent work (Breslauer et al. (1986) Proc. Natl. Acad. Sci. (U.S.A.), 83, 3746) has provided a method for calculating empirical thermodynamic quantities for helix to coil transitions from the base sequence of any oligomer. It is shown in this work that the DNA helix binding energy, calculated with the AMBER force field, for 9-mers of the type 5'-GGGXGeYGGG-3', where X and Y are any base and the central Ge is O6-ethylguanine, correlates well with the empirical delta G for helix to strand transitions. The mutation spectrum of ethane methylsulfonate (EMS) in the lacI gene of Escherichia coli can be modeled using the calculated local binding energy but the empirical free energies, enthalpies and melting temperatures predict these levels of repair less well. The relation of the binding energy to the mutation spectrum can be somewhat improved by including entropic effects in a theoretical free energy of binding as given by delta G theoretical identical to delta E binding - T delta S.
authors.affiliation: Laboratory of Molecular Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
authors.forename: C K
authors.initials: CK
authors.lastname: Foley
authors.forename: L G
authors.initials: LG
authors.lastname: Pedersen
authors.forename: T A
authors.initials: TA
authors.lastname: Darden
authors.forename: B W
authors.initials: BW
authors.lastname: Glickman
authors.forename: M W
authors.initials: MW
authors.lastname: Anderson
mesh_terms: D001483:Base Sequence; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology*; D004269:DNA, Bacterial / Q000737:chemistry* / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D013816:Thermodynamics
chemical_list: D004269:DNA, Bacterial; C007673:6-ethylguanine; D006147:Guanine; D005020:Ethyl Methanesulfonate