Biochemistry 2011
Area of Doctoral Study: Biochemistry
Research Advisor : Alex Drohat, Ph.D. (UMB)
Undergraduate Institute: Case Western Reserve University
Current Position: Research Associate, Johns Hopkins School of Medicine
Description of Research
Dr. Alex Drohat’s primary research interests focus on the structural and functional characterization of proteins known to participate in DNA repair mechanisms. As a natural condition of metabolism, cells constantly incur damage to the genome, which over time can result in mutations within genes of importance. To combat this, the cells may rely on several different pathways to repair this damage. One of these is known as the Base Excision Repair (BER) pathway. One characteristic of this pathway is that it requires a glycosylase protein, which is base-specific, and removes the damaged base, leaving an apurinic/apyramidinic site (AP-site). One project of mine pertains to a certain DNA glycosylase, TDG (Thymidine DNA Glycosylase). This protein, although named as if Thymine is its target base, actually has its highest activity within certain sequence contexts. This project deals with determining the relevance of different contexts to the kinetics of this reaction. This information will be informative in determining the exact mechanism by which the reaction occurs.
After the damaged base is removed, an AP-site still remains, which is cytotoxic if not further repaired. APE1 (Apurinic/apyramidinic Endonuclease I) catalyzes the removal of TDG from the AP-site, and hydrolyzes the sugar-phosphate backbone. This step leads to the recruitment of the proteins responsible for replacing the damaged base. Another focus of my work is centered on determining the structural composition of the APE1binding site while interacting with TDG by NMR spectroscopy.