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School of Medicine
Department Affiliation: Primary: Chemistry
Degree: Ph.D., Yale University
Telephone Number: 410-616-8095
Fax Number: 410-516-7044
E-mail address: email@example.com
Johns Hopkins Homewood Address: Department of Chemistry, NCB 313, 3400 N. Charles Street, Baltimore, MD 21218
Chemical and biochemical approaches to the study of DNA damage and repair, and their applications including the design of repair enzyme inhibitors, radiosensitizing agents, sensors for DNA lesions.
As the carrier of genetic information, DNA damage and repair is important in aging and a variety of genetically based diseases, such as cancer. Certain types of modified nucleic acids are becoming increasingly important as diagnostic tools and therapeutic agents. The pivotal roles of nucleic acids (DNA, RNA) in chemistry and biology are interwoven. For instance, the reactivity of DNA with reactive oxygen species determines the types of structural modifications (lesions) formed. The interaction of DNA lesions with repair and polymerase enzymes in turn determines their biological effects. Identifying the location and level of DNA lesions in the genome may assist the diagnosis and treatment approach of disease.
Our research group uses organic chemistry, biochemistry, and molecular biology to address questions concerning the reactivity, function, structure, and uses of nucleic acids.
Examples of recentsly completed projects in our group include:
- demonstrated that histone proteins in nucleosome core particles catalyze cleavage of damaged DNA (e.g. C4-AP) and in at least one instance this results in post-translational modification of the protein (Scheme 1).
- established the chemical foundation of how potent antitumor agents that damage DNA function by demonstrating that the DNA lesions (e.g. DOB, Scheme 2) produced irreversibly inhibit vital repair enzymes (e.g. DNA polymerase ß, Pol ß). This has provided the inspiration for the synthesis of small molecule inhibitors that exploit this chemistry.
- developing reagents and methods for the selective detection of nucleic acid lesions.
To bring these projects to fruition we synthesize novel molecules and study their behavior using a variety of physicochemical, biochemical, and biological techniques.
- Zhou, C., Sczepanski, J.T., Greenberg, M.M. Histone modification via rapid cleavage of C4'-oxidized abasic sites in nucleosome core particles. J. Am. Chem. Soc. 135:5274-5277, 2013. "Spotlighted" in the J. Am. Chem. Soc. 135:5933, 2013. Pub Med Reference
- Sczepanski, J.T., Zhou, C., Greenberg, M.M. Nucleosome core particle catalyzed strand scission at abasic sites. Biochemistry 52:2157-2164, 2013. Pub Med Reference
- Stevens, A.J., Guan, L., Bebenek, K., Kunkel, T.A., Greenberg, M.M. DNA Polymerase λ inactivation by oxidized abasic sites. Biochemistry 52:975-983, 2013. Pub Med Reference
- Resendiz, M.J.E., Schön, A., Freire, E., Greenberg, M.M. Photochemical control of RNA structure by disrupting π-stacking. J. Am. Chem. Soc. 134:12478-12481, 2012. Pub Med Reference Highlighted by Faculty 1000: http://f1000.com/prime/718008044?subscriptioncode=698beb4c-fb8a-4a37-bb37-0f3e5fc23efb#related-articles
- Zhang, B., Guo, L.-H., Greenberg, M. M. Quantification of 8-oxodGuo lesions in double-stranded DNA using a photoelectrochemical DNA sensor. Anal. Chem. 84:6048-6053, 2012. Pub Med Reference
- Zhou, C., Sczepanski, J.T., Greenberg, M. M. Mechanistic studies on histone catalyzed cleavage of apyrimidinic/apurinic sites in nucleosome core particles. J. Am. Chem. Soc. 134:16734-16741, 2012. Pub Med Reference
- Zhou, C., Greenberg, M. M. Histone catalyzed cleavage of nucleosomal DNA containing 2-deoxyribonolactone. J. Am. Chem. Soc. 134:8090-8093, 2012. "Spotlighted" in the J. Am. Chem. Soc. 134:9031. Pub Med Reference
- Jacobs, A.C., Resendiz, M.J.E., Greenberg, M. M. Product and mechanistic analysis of the reactivity of a C6-pyrimidine radical in RNA. J. Am. Chem. Soc. 133:5152-5159, 2011. Pub Med Reference
- Jacobs, A. C., Kreller, C.R., Greenberg, M. M. Long patch base excision repair compensates for DNA polymerase ß inactivation by the C4'-oxidized abasic site. Biochemistry 50:136-143, 2011. Pub Med Reference
- Sczepanski, J.T., Wong, R.S., McKnight, J.N., Bowman, G.D., Greenberg, M. M. Rapid DNA-protein cross-linking and strand scission by an abasic site in a nucleosome core particle. Proc. Natl. Acad. Sci. USA 107:22475-22480, 2010. Pub Med Reference
- Guan, L., Greenberg, M. M. Irreversible inhibition of DNA polymerase�ß by an oxidized abasic lesion. J. Am. Chem. Soc. 2010, 132, 5004-5005. Pub Med Reference
Other graduate programs in which Dr. Greenberg participates:
Chemistry Graduate Program
Chemistry-Biology Interface Program (CBI)
Graduate Program in Molecular & Computational Biophysics