Marc M. Greenberg

Department Affiliation: Primary: Chemistry
Degree: Ph.D., Yale University
Rank: Professor
Telephone Number: 410-616-8095
Fax Number: 410-516-7044
E-mail address: mgreenberg@jhu.edu
Homepage URL: http://www.chemistry.jhu.edu/Greenberg/biography.html
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:

determining the effects of specific DNA lesions (e.g. 1) on the function of nucleic acids by independently producing them at specific sights within nucleosomes and naked DNA.
determining how nucleic acids are oxidatively damaged by synthesizing molecules (e.g. 2) that enable us to independently generate reactive intermediates at defined sites in DNA and RNA.
developing reagents and methods for the selective detection of nucleic acid lesions.

Greenberg Figure

To bring these projects to fruition we synthesize novel molecules and study their behavior using a variety of physicochemical, biochemical, and biological techniques. Recent accomplishments by our research group in these areas include:

the discovery of the first example of a DNA radical (e.g. 3) that produces interstrand cross-links.
the discovery that oxidized abasic lesions (e.g. 4) uniquely interact with DNA polymerases and repair enzymes.
the development of a selective methods for detecting DNA lesions.

Representative Publications:

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
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
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
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
Peng, X., Ghosh, A. K., Van Houten, B., Greenberg, M. M. Nucleotide excision repair of a DNA interstrand cross-link produces single- and double-strand breaks. Biochemistry 49:11-19, 2010. Pub Med Reference
Sczepanski, J.T., Jacobs, A.C., Van Houten, B., Greenberg, M. M. Double-strand break formation during nucleotide excision repair of a DNA interstrand cross-link. Biochemistry 48:7565-7567, 2009. Pub Med Reference
Huang, H., Imoto, S., Greenberg, M. M. The mutagenicity of thymidine glycol in Escherichia coli is increased when it is part of a tandem lesion. Biochemistry 48:7833-7841, 2009. Pub Med Reference
Huang, H., Stivers, J.T., Greenberg, M. M. Competitive inhibition of uracil DNA glycosylase by a modified nucleotide whose triphosphate is a substrate for DNA polymerase. J. Am. Chem. Soc. 131:1344-1345, 2009. Pub Med Reference
Sczepanski, J.T., Jacobs, A.C., Majumdar, A., Greenberg, M. M. Scope and mechanism of interstrand cross-link formation by the C4'-oxidized abasic site. J. Am. Chem. Soc. 131:11132-11139, 2009. Pub Med Reference
Peng, X., Pigli, Y., Rice, P.A., Greenberg, M. M. Protein binding has a large effect on radical mediated DNA damage. J. Am. Chem. Soc. 130:12890-12891, 2008. Pub Med Reference
Huang, H., Greenberg, M. M. Hydrogen bonding contributes to the selectivity of nucleotide incorporation opposite an oxidized abasic lesion. J. Am. Chem. Soc. 130:6080-6081, 2008. Pub Med Reference