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Title page for ETD etd-02222013-142422

Type of Document Dissertation
Author Adhikary, Suraj
Author's Email Address suraj.adhikary@vanderbilt.edu
URN etd-02222013-142422
Title Structural and biochemical characterization of yeast alkylpurine DNA glycosylases
Degree PhD
Department Biological Sciences
Advisory Committee
Advisor Name Title
Katherine L. Friedman Committee Chair
Brandt Eichman Committee Member
Charles K. Singleton Committee Member
Neil Osheroff Committee Member
  • DNA glycosylase
  • DNA repair
  • structural biology
  • X-ray crystallography
Date of Defense 2013-01-14
Availability unrestricted
Work presented in this dissertation details structural and biochemical characterization of three yeast alkylpurine DNA glycosylases – Mag1 and Mag2 from S. pombe and Mag from S. cerevisiae. I determined high resolution crystal structures all three enzymes and used the structures to initiate a deeper understanding of the sources of substrate specificity and catalytic competence in DNA glycosylases. My study of Mag1 and Mag provided novel evidence that protein-DNA interactions away from the active site can modulate the specificity of DNA glycosylases and a single substitution in the minor-groove interrogating loop is sufficient to alter the preference of one alkylpurine glycosylase for εA to that of a homologous enzyme. The crystal structure of Mag2 along with biochemical and phylogenetic analysis of the Mag genes in related fungal species studies showed that spMag2 cannot form a catalytically competent complex with DNA due to differences in the minor-groove interrogating loop and overall electrostatic surface potential compared to other alkylpurine glycosylases and may have evolved to perform a separate function.
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