Professor
Department of Chemistry
Krieger School of Arts & Sciences

mgreenberg@jhu.edu

313 New Chemistry Building
3400 N. Charles Street
Baltimore, MD 21218

Office: 410-516-8095
Lab: 410-516-8143

As the carrier of genetic information, the damage and repair of DNA is crucial to survival. Studying these processes at the molecular level is complicated by the fact that DNA is a heterogeneous polymer, and that it has been difficult to control where damage occurs. Our research group uses chemistry and biology to study how DNA is oxidatively damaged, how damage affects DNA structure and function, and how this damage is repaired. These ongoing investigations have inspired new projects in which we apply the fundamental knowledge acquired from examining DNA damage and repair at the molecular level.

We use chemistry to produce the reactive intermediates, metastable products, and lesions that are generated by gamma radiolysis, antitumor agents, and exogenous oxidants, at defined sites in DNA. These processes are characterized using a diverse set of methods that include physical, biochemical, and molecular biology techniques. This one molecule one "lesion" strategy has both simplified investigations and revealed chemical complexities that were not detectable previously. For example, using this general approach we:

• Discovered the first example of DNA-DNA interstrand cross-link formation by a nucleic acid radical that is produced as a result of oxidative stress.
• Uncovered novel pathways for the formation of tandem lesions that are produced during exposure of DNA to gamma radiolysis. These tandem lesions may have significant biological effects.
• Developed sensors that selectively detect DNA lesions.
• Discovered that the in vitro and in vivo effects of oxidized abasic lesions are unique and biologically significant.
• Determined that polymerases use hydrogen bonding to decide which nucleotide(s) to incorporate opposite an abasic lesion, despite the absence of a Watson-Crick base.
  

Selected Publications
Huang, H., and M.M. Greenberg. (2008) Hydrogen bonding contributes to the selectivity of nucleotide incorporation opposite an oxidized abasic lesion by DNA polymerase. J. Am. Chem. Soc. 130:6080-6081.

Sczepanski, J.T., A.C. Jacobs, and M.M. Greenberg. (2008) Self-promoted DNA interstrand cross-link formation by an abasic site. J. Am. Chem. Soc. 130:9646-9647.

Peng, X., I.S. Hong, H. Li, M.M. Seidman, and M.M. Greenberg. (2008) Interstrand cross-link formation in duplex and triplex DNA by modified pyrimidines. J. Am. Chem. Soc. 130:10299-10306.

Dhar, S., T. Kodama, and M.M. Greenberg. (2007) Selective detection and quantification of oxidized abasic lesions in DNA. J. Am. Chem. Soc. 129:8702-8703.

Ding, H., and M.M. Greenberg. (2007) 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.

Xue, L., and M.M. Greenberg. (2007) Use of fluorescence 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.

Xue, L., and M.M. Greenberg. (2007) Facile quantification of lesions derived from 2'-deoxyguanosine in DNA. J. Am. Chem. Soc. 129:7010-7011.

Hong, I.S., K.N. Carter, K. Sato, and M.M. Greenberg. (2007) Characterization and mechanism of formation of tandem lesions in DNA by a nucleobase peroxyl radical. J. Am. Chem. Soc. 129:4089-4098.

Hong, I.S., H. Ding, and M.M. Greenberg. (2006) Radiosensitization by a modified nucleotide that produces DNA interstrand cross-links under hypoxic conditions. J. Am. Chem. Soc. 128:2230-2231.

Hong, I.S., H. Ding, and M.M. Greenberg. (2006) Oxygen independent DNA interstrand cross-link formation by a nucleotide radical. J. Am. Chem. Soc. 128:485-491.