Department Affiliation: Primary: Chemistry
Degree: Ph.D., Yale University
Rank: Professor
Telephone Number: 410-516-8095
Fax Number: 410-516-7044
E-mail address: mgreenberg@jhu.edu
Homepage URL: http://www.jhu.edu/chem/greenberg/index.htm
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.
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 current projects in our group are:
- determining how nucleic acids are oxidatively damaged by synthesizing molecules (e.g. 1) that enable us to independently generate reactive intermediates at defined sites in DNA.
- elucidating the effects of specific DNA lesions (e.g. 2) on the function of nucleic acids, and their structural basis.
- developing reagents (e.g. 3) 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. Recent accomplishments by our research group in these areas include:
- the discovery of the first example of a DNA radical that produces interstrand cross-links.
- the discovery of novel pathways for DNA damage that produce tandem lesions.
- the discovery that oxidized abasic lesions (e.g. 2) uniquely interact with DNA polymerases and repair enzymes.
- the development of a selective methods for detecting DNA lesions.
Representative Publications:
- Xue, L., and Greenberg, M. M. Use of Fluorescent Sensors to Determine that 2-Deoxyribonolactone is the Major Alkali-Labile Deoxyribose Lesion Produced in Oxidatively Damaged DNA. Angew. Chem. Int. Ed. 46:561-564, 2007. Pub Med Reference
Ding, H. and Greenberg, M. M. Hole Migration is the Major Pathway Involved in Alkali-Labile Lesion Formation in DNA by the Direct Effect of Ionizing Radiation. J. Am. Chem. Soc. 129:772-773, 2007. Pub Med Reference
Hong, I.S., Carter, K.N., Sato, K. and Greenberg, M.M. Characterization and Mechanism of Formation of Tandem Lesions in DNA by a Nucleobase Peroxyl Radical. J. Am. Chem. Soc. 129:4089-4098, 2007. Pub Med Reference
- Xue, L.; Greenberg, M. M. Facile Quantification of Lesions Derived from 2'-Deoxyguanosine in DNA. J. Am. Chem. Soc. 2007, 129, 7010-7011. Pub Med Reference
- Ding, H. and Greenberg, M. M. Gamma-Radiolysis Produces Interstrand Cross-links in DNA Involving Thymidine. Chem. Res. Toxicol. 20:1623-1628, 2007. Pub Med Reference
- Dhar, S.; Kodama, T.; Greenberg, M. M. Selective Detection and Quantification of Oxidized Abasic Lesions in DNA. J. Am. Chem. Soc. 2007, 129, 8702-8703. Pub Med Reference
- Peng, X. and Greenberg, M. M. Facile SNP Detection Using Bifunctional, Cross-Linking Oligonucleotide Probes. Nucleic Acids Res. 36: e31, 2008. Pub Med Reference
- Huang, H. and Greenberg, M. M. Hydrogen Bonding Contributes to the Selectivity of Nucleotide Incorporation Opposite an Oxidized Abasic Lesion by DNA Polymerase. J. Am. Chem. Soc. 130:6080-6081, 2008. Pub Med Reference
- Sczepanski, J. T., Jacobs, A. C., Greenberg, M. M. Self-Promoted DNA Interstrand Cross-link Formation by an Abasic Site. J. Am. Chem. Soc. 130:9646-9647, 2008. Pub Med Reference
- Peng, X., Hong, I. S., Li, H., Seidman, M.M., and Greenberg, M. M. Interstrand Cross-link Formation in Duplex and Triplex DNA by Modified Pyrimidines. J. Am. Chem. Soc. 130:10299-10306, 2008. Pub Med Reference
- Peng, X., Pigli, Y., Rice, P.A., and 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
- Ding, H., Majumdar, A., Tolman, J.R. and Greenberg, M. M. Multinuclear NMR and Kinetic Analysis of DNA Interstrand Cross-link Formation. J. Am. Chem. Soc. 130:17981-17987, 2008. Pub Med Reference
- Huang, H., Stivers, J.T. and 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. and 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
- Sczepanski, J.T., Jacobs, A.C., Van Houten, B. and 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. and Greenberg, M. M. The Deleterious Effects of Thymidine Glycol on Replication in E. coli are Exacerbated When Part of a Tandem Lesion. Biochemistry 48:7833-7841, 2009. 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
