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Michael P. Stone

Title and Contact Information

Professor & Department Chairman
Office: 5524 SC
Phone: (615) 322-2589
EmailWebsite

Education

Ph.D., University of California, Irvine, 1981

Specialties

VICB
Physical Chemistry
Chemical Biology
Center for Structural Biology
Biochemistry

In the News

VICC-Device to Give Peek into Protein Structures
AAAS-Professor Stone elected as 2010 Fellow Award

Stone

Research

Biophysical Chemistry

DNA damage is believed to represent the initiating step in chemical carcinogenesis. Our laboratory seeks to understand how specific DNA adducts perturb DNA structure and how these structural interfere with the biological processing of DNA. One goal is to understand the basis whereby chemical modification of DNA triggers specific mutations. Some mutations, especially those occurring in proto-oncogene sequences or tumor suppressor gene sequences, play crucial roles in the process of chemical carcinogenesis. Some fundamental questions under study are:
  • How do specific DNA adducts alter the three dimensional structure of DNA?
  • How does adduction affect the biological processing of DNA during replication and repair?
  • How do specific DNA adducts alter the three dimensional structure of primer-template complexes with damage bypass polymerases?
  • What is the role of DNA sequence in modulating adduct conformation and biological processing?

Both NMR spectroscopy and X-ray crystallography play major roles in our research program. Our laboratory is affiliated with the Vanderbilt Center in Structural Biology. NMR spectroscopy is used to determine the three dimensional structures and dynamics of site-specifically adducted oligodeoxynucleotides in aqueous solution. Crystallographic approaches allow the structural determination of larger biomolecular complexes involving DNA processing enzymes.



Space-filling model of an oligodeoxynucleo-tide containing a mutagenic lesion, 1,N2 -propanodeoxyguanosine. The model was refined using experimental NOE constraints derived from 1H NMR spectroscopy.

Selected Publications

Kowal, E. A., Lad, R. R., Pallan, P. S., Dhummakupt, E., Wawrzak, Z., Egli, M., Sturla, S. J., Stone, M. P. Recognition of O-6-benzyl-2'-deoxyguanosine by a perimidinone-derived synthetic nucleoside: a DNA interstrand stacking interaction. Nucleic Acids Research. 2013, 41 (15): 7566-7576.  

Shanmugam, G., Minko, I. G., Banerjee, S., Christov, P. P., Kozekov, I. D., Rizzo, C. J., Lloyd, R. S., Egli, M., Stone, M. P. Ring-Opening of the gamma-OH-PdG Adduct Promotes Error-Free Bypass by the Sulfolobus solfataricus DNA Polymerase Dpo4. Chemical Research in Toxicology. 2013, 26 (9): 1348-1360.  

Szulik, M. W., Voehler, M. W., Ganguly, M., Gold, B., Stone, M. P. Site-Specific Stabilization of DNA by a Tethered Major Groove Amine, 7-Aminomethyl-7-deaza-2 '-deoxyguanosine. Biochemistry. 2013, 52 (43): 7659-7668.  

Ganguly, M., Szulik, M. W., Donahue, P. S., Clancy, K., Stone, M. P. Thermodynamic Signature of DNA Damage: Characterization of DNA with a 5-Hydroxy-2 '-deoxycytidine center dot 2 '-Deoxyguanosine Base Pair. Biochemistry. 2012, 51 (9): 2018-2027.  

Huang, H., Das, R. S., Basu, A. K., Stone, M. P. Structures of (5 ' S)-8,5 '-Cyclo-2 '-deoxyguanosine Mismatched with dA or dT. Chemical Research in Toxicology. 2012, 25 (2): 478-490.  

Banerjee, S., Christov, P. P., Kozekova, A., Rizzo, C. J., Egli, M., Stone, M. P. 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.  

Ganguly, M., Szulik, M. W., Donahue, P. S., Clancy, K., Stone, M. P., Gold, B. Thermodynamic Signature of DNA Damage: Characterization of DNA with a 5-Hydroxy-2 '-deoxycytidine center dot 2 '-Deoxyguanosine Base Pair. Pharmazeutische Industrie. 2012, 74 (2): 2018-2027.  

Stone, M. P., Huang, H., Brown, K. L., Shanmugam, G. Chemistry and Structural Biology of DNA Damage and Biological Consequences. Chemistry & BioDiversity. 2011, 8 (9): 1571-1615.  

Kowal, E. A., Ganguly, M., Pallan, P. S., Marky, L. A., Gold, B., Egli, M., Stone, M. P. Altering the Electrostatic Potential in the Major Groove: Thermodynamic and Structural Characterization of 7-Deaza-2 '-deoxyadenosine:dT Base Pairing in DNA. Journal of Physical Chemistry B. 2011, 115 (47): 13925-13934.  

Singh, S. K., Szulik, M. W., Ganguly, M., Khutsishvili, I., Stone, M. P., Marky, L. A., Gold, B. Characterization of DNA with an 8-oxoguanine modification. Nucleic Acids Research. 2011, 39 (15): 6789-6801.  

Banerjee, S., Brown, K., L., Egli, M., Stone, M. P. Bypass of aflatoxin B1 adducts by the Sulfolobus solfataricus DNA polymerase IV. Journal of the American Chemical Society. 2011, 133 (3): 12556-12568.  

Shanmugam, G., Kozekov, I. D., Guengerich, F. P., Rizzo, C. J., Stone, M. P. 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.  
 
Huang, H., Wang, H., Voehler, M. W., Kozekova, A., Rizzo, C. J., McCullough, A. K., Lloyd, R. S., Stone, M. P. 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.   

Brown, K. L., Roginskaya, M., Zou, Y., Altamirano, A., Basu, A. K., Stone, M. P. Binding of the human nucleotide excision repair proteins XPA and XPC/HR23B to the 5R-thymine glycol lesion and structure of the cis-(5R,6S) thymine glycol epimer in the 5'-GTgG-3' sequence: destabilization of two base pairs at the lesion site. Nucleic Acids Research. 2010, 38 (2): 428-440.  
  
 

Shanmugam, G., Kozekov, I. D., Guengerich, F. P., Rizzo, C. J., Stone, M. P. 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.    

Huang, H., Kozekov, I. D., Kozekova, A., Rizzo, C. J., McCullough, A. K., Lloyd, R. S., Stone, M. P. 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.

Huang, H., Kozekov, I. D., Kozekova, A., Wang, H., Lloyd, R. S., Rizzo, C. J., Stone, M. P. DNA Cross-Link Induced by trans-4-Hydroxynonenal. Environmental and Molecular Mutagenesis. 2010, 51 (6): 625-634.

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