NMR Solution Structure of Nucleic Acids
and Proteins

Carlos de los Santos, Ph.D.
Research Assistant Professor, Pharmacological Sciences
Ph.D., University of Buenos Aires, Argentina
Postdoctoral, College of Physicians and Surgeons,
Columbia University and Sloan-Kettering Institute
Columbia University and Sloan-Kettering Institute

Selected Publications

Research in our laboratory focuses on the determination of the solution structure DNA molecules damaged by endogenous and exogenous agents, and to establish structure-function relationships relating to mutagenesis and DNA repair. We use solution state nuclear magnetic resonance spectroscopy, NMR, in combination with restrained molecular dynamics simulations, to establish the conformation of DNA duplexes and proteins at atomic resolution. Currently, we are studying the structure of duplexes containing exocyclic lesions, such as etheno-dC, etheno-dG and acrolein-dG adducts, which result from the reaction of DNA with lipid peroxidation products. The systematic approach implemented in our studies allowed us to assess the impact of DNA sequence context in the duplex stability and conformation. In addition, our findings identifed the protein recognition elements present in εdC-containing duplex substrates, a fact that explains their recognition by the MUG and hTDG the repair enzymes.

Another area of research is the structural characterization of DNA duplex containing clustered lesions produced by ionizing radiation, which have been implicated in long-term cytotoxic effects of gamma radiation.

Selected Publications

Korobka, A., Cullinan, D., Cosman, M., Grollman, A. P., Patel, D. J., Eisenberg, M., & de los Santos C. (1996) Solution Structure of an Oligonucleotide Duplex Containing the Exocyxlic Lesion 3,N⁴-Etheno-2’-deoxycytidine Opposite 2’-deoxyadenosine Determined by NMR Spectroscopy and Restrained Molecular Dynamics. Biochemistry 35, 13310-13318.

Cullinan, D., Korobka, A., Grollman, A. P., Patel, D. J., Eisenberg, M., & de los Santos C. (1996) NMR Solution Structure of an Oligodeoxynucleotide Duplex Containing the Exocyxlic Lesion 3,N⁴-Etheno-2’-deoxycytidine Opposite Thymidine: Comparison with the Duplex Containing Deoxyadenosine Opposite the Adduct. Biochemistry 35, 13319-13327.

Cullinan, D., Grollman, A. P., Eisenberg, M., & de los Santos, C. (1997) Solution Structure of a DNA Duplex Containing the Exocyclic Lesion: 3,N⁴-Etheno-2’-deoxycytidine Opposite 2’-deoxyguanosine. Biochemistry 36, 11933-11943.

Lin, Z., Hung, K-N., Grollman, A. P., & de los Santos, C. (1998) Solution Structure of Duplex DNA Containing an Extrahelical Abasic Site Analog Determined by NMR Spectroscopy and Molecular Dynamics. Nucleic Acids Res. 10, 2385-2391.

de los Santos, C. Probing DNA Structure by NMR, in “Comprehensive Natural Products Chemistry”, D. Barton and K. Nakanishi, eds. Elsevier Science, 1999, vol. 7, 55-80.

Cullinan, D., Eisenberg, M. & de los Santos, C. (1999) Solution Structure of DNA Duplexes Containing the Exocyclic Lesion: 3,N⁴-Etheno-2’-deoxycytidine. in "Exocyclic DNA Adducts in Mutagenesis and Carcinogenesis", B. Singer and H. Bartsch, eds. IARC Scientific Publications, 150, 179-189.

Cullinan, D., Johnson, F & de los Santos, C. (2000) Solution Structure of an 11-mer Duplex Containing the 3,N⁴-ethenocytosine Adduct Opposite 2’-Deoxycytidine. Implications for the Recognition of Exocyclic Lesions by DNA Glycosylases. J. Mol. Biol. 296, 851-861.

Smirnov, S., Johnson, F., Marumoto, R. & de los Santos, C. (2000) Solution Structure of an 11-mer DNA Duplex Containing the Carbocyclic Nucleotide Analog: 2’-deoxyaristeromycin. J. Biomol. Struct. & Dyn. (in press).