A series of specifically modified, complementary deoxyribodecanucleotides (decamer) will be synthesized by the phosphotriester method. The modifications will include: (1) alkylated bases such as O6-ethylguanine, O4 ethylthymine and N3-methylcytosine, (2) alkylated phosphate groups (phosphotriesters), and (3) apurinic and apyrimidinic sites. These types of modifications are found in cellular nucleic acids after treatment with mutagenic and carcinogenic alkylating agents. The decamers will be capable of forming short DNA helices and duplexes in solution, with modificatons occurring in the central dimer region of the helix. Thus the helices will serve as models for DNA which has been altered by reaction with alkylating agents. The stability and thermodynamic properties of the modified helices will be studied by ultraviolet spectroscopic techniques. The overall mode of the base stacking in the modified helices will be observed by circular dichroism (CD) spectroscopic techniques. Proton and phosphorus nuclear magnetic resonance (NMR) spectroscopy will be used to study the conformation of the modified helices. Of particular interest will be the study of the perturbational effects of base and phosphate alkylation on the local conformation at the site of modification and to determine if these effects are propogated throughout the helix. The modified helices and duplexes will be tested for their ability to serve as model substrates for enzymes involved in DNA replication and repair including DNA polymerase, DNA ligase, DNA N-glycosylase and DNA apurinic endonuclease. The results of the physical studies will be correlated with the results of the biochemical studies.