Wesleyan portrait of Brandon  Case

Brandon Case

Graduate Student, MB&B-PHD


bcase@wesleyan.edu

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Brandon Case

Brandon is a graduate student in the Hingorani Lab utilizing transient kinetic methods coupled with spectrophotometric detection to understand the mechanisms of DNA mismatch repair (MMR) and nucleotide excision repair (NER).

MMR: During replication, polymerases can incorporate mismatched nucleotides in the DNA. To maintain genomic integrity, the evolutionarily conserved MutS and MutL proteins work together in the initial steps of the DNA mismatch repair pathway. After locating a mismatch, MutS recruits MutL to the error-containing strand and activates MutL endonuclease activity to nick the DNA. Downstream proteins then remove the error-containing strand and resynthesize the DNA. How MutS and MutL interact to achieve this goal, however, is not known. Research is currently focused on understanding the interaction between MutS and MutL as well as the specificity of MutS-dependent MutL endonuclease activity.

NER: Exposure to UV and oxidative damages leads to an accumulation of DNA lesions. Repairing these damages is the responsibility of the NER pathway, which is initiated by UvrA in bacteria. In its functional form, the UvrA dimer couples its ATPase and DNA binding activities to lesion detection and signals for repair by recruiting UvrB. Interestingly, each UvrA monomer contains two nucleotide binding domains, giving the dimer a total of four ATPase sites. Previous studies aimed at understanding how UvrA couples its two activities lacked stoichiometric and temporal information needed to define the ATPase mechanism at each site. Using a pre-steady state approach, we hope to address the ATPase mechanism of UvrA alone, in the presence of matched DNA and in the presence of a lesion to improve our understanding of lesion recognition and NER initiation.

Before coming to Wesleyan, Brandon attended Western New England University and received a BS in Chemistry. As an undergraduate, Brandon worked under the supervision of Dr. Anne F. Poirot investigating potential synergistic effects of DTT and chlorpyrifos on acetylchonlinesterase activity. Once he was determined to gain a better understanding of enzyme kinetics, Brandon came to Connecticut to attend graduate school in the Molecular Biology and Biochemistry department at Wesleyan University. At Wesleyan, Brandon works in Dr. Manju Hingorani's laboratory studying the mechanisms of DNA repair enzymes using a transient kinetic approach.