个人简介

Ph.D., University of Pennsylvania, 1990

研究领域

Organic Chemistry Chemical Biology Bioorganic Chemistry

Covalent modification of DNA by electrophiles is generally accepted as the initial event in chemical carcinogenesis. If these modifications are not repaired, they can compromise the fidelity of DNA replication leading to mutations and possibly cancer. To properly study the biological processing of pre-mutagenic DNA lesions, oligonucleotides containing structurally defined carcinogen adducts are required. Our laboratory develops synthetic strategies for the site-specific incorporation of nucleotides that are chemically modified by carcinogens into DNA. Once synthesized, the structure, replication and repair of the carcinogen-modified oligonucleotides are examined. Many of these studies are preformed in collaboration with other laboratories on Vanderbilt's campus and elsewhere.

近期论文

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Stavros KM, Hawkins EK, Rizzo CJ, Stone MP. Base-displaced intercalation of the 2-amino-3-methylimidazo[4,5-f]quinolone N2-dG adduct in the NarI DNA recognition sequence. Nucleic Acids Research. 2014, 42 (5): 3450-63. Maddukuri L, Shuck SC, Eoff RL, Zhao LL, Rizzo CJ, Guengerich FP, Marnett LJ. Replication, Repair, and Translesion Polymerase Bypass of N-6-Oxopropenyl-2 '-deoxyadenosine. Biochemistry. 2013, 52 (48): 8766-8776. Zhao LL, Pence MG, Christov PP, Wawrzak Z, Choi JY, Rizzo CJ, Egli M, Guengerich FP. Basis of Miscoding of the DNA Adduct N-2,3-Ethenoguanine by Human Y-family DNA Polymerases. Journal of Biological Chemistry. 2013, 287 (42): 35516-35526. Christov PP, Yamanaka K, Choi JY, Takata KI, Wood RD, Guengerich FP, Lloyd RS, Rizzo CJ. Replication of the 2,6-Diamino-4-hydroxy-N-5-(methyl)-formamidopyrimidine (MeFapy-dGuo) Adduct by Eukaryotic DNA Polymerases. Chemical Research in Toxicology. 2012, 25 (8): 1652-1661. Zhao LL, Christov PP, Kozekov ID, Pence MG, Pallan PS, Rizzo CJ, Egli M, Guengerich FP. Replication of N2,3-Ethenoguanine by DNA Polymerases. Angewandte Chemie-International Edition. 2012, 51 (22): 5466-5469. Banerjee S, Christov PP, Kozekova A, Rizzo CJ, Egli M, Stone MP. Replication Bypass of the trans-4-Hydroxynonenal-Derived (6S,8R,11S)-1,N-2-Deoxyguanosine DNA Adduct by the Sulfolobus solfataricus DNA Polymerase IV. Chemical Research in Toxicology. 2012, 25 (2): 422-435. Huang H, Wang H, Kozekova A, Rizzo CJ, Stone MP. Formation of a N(2)-dG:N(2)-dG Carbinolamine DNA Cross-link by the trans-4-Hydroxynonenal-Derived (6S,8R,11S) 1,N(2)-dG Adduct. Journal of The American Chemical Society. 2011, 133 (40): 16101-16110. Huang H, Wang H, Voehler MW, Kozekova A, Rizzo CJ, McCullough AK, Lloyd RS, Stone MP. gamma-Hydroxy-1,N(2)-propano-2 '-deoxyguanosine DNA Adduct Conjugates the N-Terminal Amine of the KWKK Peptide via a Carbinolamine Linkage. Chemical Research in Toxicology. 2011, 24 (7): 1123-1133. Shanmugam G, Kozekov ID, Guengerich FP, Rizzo CJ, Stone MP. 1,N(2)-Etheno-2 '-deoxyguanosine Adopts the syn Conformation about the Glycosyl Bond When Mismatched with Deoxyadenosine. Chemical Research in Toxicology. 2011, 24 (7): 1071-1079. Petrova KV, Stec DF, Voehler M, Rizzo CJ, Jeong BS. Synthesis of the four stereoisomers of 2,3-epoxy-4-hydroxynonanal and their reactivity with deoxyguanosine. Organic Biomolecular Chemistry. 2011, 9 (6): 1960-71. Maddukuri L, Eoff RL, Choi J-Y, Rizzo CJ, Guengerich FP, Marnett LJ. In Vitro Bypass of the Major Malondialdehyde- and Base Propenal-Derived DNA Adduct by Human Y-family DNA Polymerases kappa, iota, and Rev1. Biochemistry. 2010, 49 (38): 8415-8424. Christov PP, Petrova KV, Shanmugam G, Kozekov ID, Kozekova A, Guengerich FP, Stone MP, Rizzo CJ. Comparison of the in Vitro Replication of the 7-(2-Oxoheptyl)4,N-2-etheno-2 '-deoxyguanosine and 1,N-2-Etheno-2 '-deoxyguanosine Lesions by Sulfolobus solfataricus P2 DNA Polymerase IV (Dpo4). Chemical Research in Toxicology. 2010, 23 (8): 1330-1341. Huang H, Kozekov ID, Kozekova A, Rizzo CJ, McCullough AK, Lloyd RS, Stone MP. Minor Groove Orientation of the KWKK Peptide Tethered via the N-Terminal Amine to the Acrolein-Derived 1,N-2-gamma-Hydroxypropanodeoxyguanosine Lesion with a Trimethylene Linkage. Biochemistry. 2010, 49 (29): 6155-6164. Yamanaka K, Minko IG, Takata K, Kolbanovskiy A, Kozekov ID, Wood RD, Rizzo CJ, Lloyd RS. Novel Enzymatic Function of DNA Polymerase v in Translesion DNA Synthesis Past Major Groove DNA-Peptide and DNA-DNA Cross-Links. Chemical Research in Toxicology. 2010, 23 (3): 689-695. Maddukuri L, Eoff RL, Rizzo CJ, Guengerich FP, Marnett LJ. Translesion DNA Synthesis across the M1dG Lesion Catalyzed by Y-Family Human DNA Polymerase Kappa (kappa). Chemical Research in Toxicology. 2010, 23 (1): 271-271. Shanmugam G, Kozekov ID, Rizzo CJ, Egli M, Stone MP. Crystal Structures of Ternary Complexes of the Y-Class Sulfolobus solfataricus DNA Polymerase Dpo4 with a Template Containing a Reduced Analog of the Acrolein-Derived Deoxyguanosine Adduct N-2-(3-Hydroxyl-propyl)-deoxyguanosine. Chemical Research in Toxicology. 2010, 23 (1): 270-270. Liu MM, Bandaru V, Bond JP, Jaruga P, Zhao XB, Christov PP, Burrows CJ, Rizzo CJ, Dizdaroglu M, Wallace SS. The mouse ortholog of NEIL3 is a functional DNA glycosylase in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America. 2010, 107 (11): 4925-4930. Shanmugam G, Kozekov ID, Guengerich F, Rizzo CJ, Stone MP. Structure of the 1,N-2-Etheno-2 '-deoxyguanosine Lesion in the 3 '-G(epsilon dG)T-5 ' Sequence Opposite a One-Base Deletion. Biochemistry. 2010, 49 (12): 2615-2626. Christov PP, Chowdhury G, Garmendia CA, Wang F, Stover JS, Elmquist CE, Kozekova A , Angel KC, Turesky RJ, Stone MP, Guengerich FP, Rizzo CJ. The C8-2 '-Deoxyguanosine Adduct of 2-Amino-3-methylimidazo[1,2-d]naphthalene, a Carbocyclic Analogue of the Potent Mutagen 2-Amino-3-methylimidazo[4,5-f]quinoline, Is a Block to Replication in Vitro. Chemical Research in Toxicology. 2010, 23 (6): 1076-1088.