De los Santos


Ph.D.: University of Buenos Aires, Argentina

Postdoctoral: Columbia University and Memorial Sloan-Kettering Cancer Institute

NMR Solution Structure of Nucleic Acids and Proteins

Research in my laboratory focuses on chemical toxicology understanding how endogenous and exogenous compounds react with DNA bases and change the structure and function of the genes. We determine the solution structures of damaged DNA molecules relating them to DNA mutagenesis and repair. Our main tools are solution state nuclear magnetic resonance (NMR) spectroscopy and restrained molecular dynamics simulations, which in combination can establish the conformation of duplex DNA duplexes and protein at atomic resolution. We are interested in exocyclic DNA adducts, such as ‘etheno’ and ‘acrolein’ lesions, that result from the reaction of endogenous lipid peroxidation products and DNA. In addition, we are looking at abasic sites, 8-oxo-guanine, fapy and 5’-8-cyclopurines, lesions that are steadily present in genomic DNA due to the reaction of oxygen radicals, produced during mitochondrial respiration, and purine bases. Another area of research is the characterization of DNA containing clustered lesions. This type of damage, produced exclusively by ionizing radiation, plays a key role in the cytotoxic properties of gamma radiation. We are also looking at exogenous gene toxicants, such as Aristolochic acids, acetylamino-fluorene, and nitro-benzanthrones, all of which are strong mutagens and mammalian carcinogens. Our hypothesis is that the systematic structural characterization of damaged DNA will permit the mechanistic understanding of chemical genotoxicity, uncover novel protein-DNA interactions and identify useful biomarkers of exposure and disease rick.


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Recent Publications


Lukin, M. & de los Santos, C. (2010) Stereoselective Nucleoside Deuteration for NMR Studies of DNA. Nucleosides, Nucleotides Nucleic Acids (in press).

Bergonzo, C., Song, K., de los Santos, C., Grollman, A. & Simmerling, C (2010) Dynamic Behavior of DNA Duplexes Suggests a Mechanism for Selective Destabilization of Lesions by a DNA Glycosylase. Nucleic Acids Res (in press)

Zaliznyak, T., Lukin, El-khateeb, M., Johnson, F. & de los Santos, C. (2010) Structure of Duplex DNA containing an a-OH-PdG•dA mismatch: the intermediate of acrolein-induced mutagenesis. Biopolymers, 93, 391-401.

Zaliznyak, T., Bonala, R., Attaluri S., Johnson, F. & de los Santos, C. (2009) Structure of Duplex DNA containing a-OH-PdG: the mutagenic adduct produced by acrolein. Nucleic Acids Res. 37, 2153-2163.

Lukin, M., Zaliznyak, T., & de los Santos, C (2009) Stereoselectivelly deuterated nucleosides for NMR studies of DNA. J. Biomol. Struct. & Dyn. 26, 897-898.

Song, K., Campbell, A.J., Bergonzo, C., de los Santos, C., Grollman, A.P. & Simmerling, C. (2009) An Improved Reaction Coordinate for Nucleic Acid Base Flipping Studies. J. Chem. Theo. Comput. 5, 3105–3113.

Song, K., Hornak, V., de los Santos, C., Grollman, A. and Simmerling, C. (2008) “Molecular Mechanics Parameters for the FapydG DNA lesion” J. Comput. Chem 29, 17-23.

Song, K., de los Santos, C., Grollman, A.P. & Simmerling, C. (2008) Molecular simulations reveal a common binding mode for glycosylase binding of oxidatively damaged DNA lesions.  J. Am. Chem. Soc. 129, 14536-14537.

Zaliznyak, T., Lukjin, M., Johnson, F., & de los Santos, C. (2008) NMR Characterization of a DNA Duplex Containing the Exocyclic 1,N2-etheno-dG Adduct. Biochemistry 47, 4606-4613.

Hazel, R., Tian, K., & de los Santos, C. (2008) NMR Solution Structures of Bi-stranded Abasic Site Lesions in DNA Biochemistry 47,11909-11919.


Selected Earlier Publications


Perillo, I., Caterina, M. C., de los Santos, C. & Salerno, A. (2007) 1H and 13C NMR Analysis of a 1,2-Diaryl-3-methyl-4,5-dihydro-1h-imidazolium Salts Series. Heterocycles 71, 49-60.

Lukin, M & de los Santos, C. (2006) NMR Structural Studies of Damaged DNA. Chem. Rev. 106, 607-686.

Zaliznyak, T., Bonala, R., Johnson, F., & de los Santos, C (2006) Structure and Stability of DNA Containing the 3-(Deoxyguanosin-N(2)-yl)-2-acetylaminofluorene (dG(N(2))-AAF) Lesion: A Bulky Adduct that Persists in Cellular DNA. Chem. Res. Toxicol. 19, 745-752. 

Song, K., Hornak, V., de los Santos, C., Grollman, A. P. & Simmerling, C. (2006) Computational Analysis of the Binding Mode of 8-oxo-guanine to the Formamidopyrimidine-DNA Glycosylase. Biochemistry 45 10886-10894.

Bohon, J. & de los Santos, C. (2005) Effect of 6-thioguanine on the stability of duplex DNA (in Nucleic Acids Res. 33, 2879-2886.

Cheng, X., Hornak, V., de los Santos, C., Grollman, A. P. & Simmerling, C. (2005) Dynamic behavior of DNA base pairs containing 8-oxoguanine. J. Am. Chem. Soc. 127, 13906-13918.

McTigue, M. M., Rieger, R. A., Rosenquist, T. A., Iden, C. R., & de los Santos, C. R. (2004) Stereoselective Excision of Thymine Glycol Lesions by Mammalian Cell Extracts. DNA Repair 3, 313-322.

de los Santos, C, El-khateeb, M., Rege, P., Tian, K. & Johnson, F. (2004) Structural Impact of C1’(OH) Conformation on Duplex DNA Containing Abasic Sites. Biochemistry 43, 15349-15357.

Perillo, I. A., de los Santos, C., & Salerno, A. (2003) Spectroscopic Analysis of Imidazolidines: Part III: 1H NMR Spectroscopy and Conformational Analysis of N-Benzylimidazolidines. Heterocycles  60, 89-98.

Bohon, J. & de los Santos, C. (2003) Structural Impact of the Anticancer Agent 6-Thioguanine in Duplex DNA. Nucleic Acids Res. 31, 1331-1338.

Tian, K., McTigue, M., & de los Santos, C. (2002) Sorting the Consequences of Ionizing Radiation: Processing of 8-Oxoguanine/Abasic Site Lesions. DNA Repair 1, 1039-1049.

Smirnov, S., Matray, T. J., Kool, E. T., & de los Santos, C. (2002) Integrity of Duplex Structures without Hydrogen Bonding: DNA with Pyrene Paired at Abasic Sites. Nucleic Acids Res. 30, 5561-5569.

de los Santos, C., Zaliznyak, T., & Johnson , F. (2001) NMR Characterization of a DNA Duplex Containing the Major Acrolein-derived Deoxyguanosine Adduct g-OH-1,N2-propano-2’-deoxyguanosine J. Biol. Chem. 276, 9077-9082.

Lin, Z. & de los Santos, C. (2001) NMR Characterization of Clustered Bistrand Abasic Site Lesions: Effect of Orientation on their Solution Structure J. Mol. Biol. 308, 341-352.

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. 17, 981-991.

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.

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.

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.