dc.creator | Adhikary, Suraj | |
dc.date.accessioned | 2020-08-21T21:03:09Z | |
dc.date.available | 2014-03-04 | |
dc.date.issued | 2013-03-04 | |
dc.identifier.uri | https://etd.library.vanderbilt.edu/etd-02222013-142422 | |
dc.identifier.uri | http://hdl.handle.net/1803/10609 | |
dc.description.abstract | 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. | |
dc.format.mimetype | application/pdf | |
dc.subject | DNA glycosylase | |
dc.subject | DNA repair | |
dc.subject | structural biology | |
dc.subject | X-ray crystallography | |
dc.title | Structural and biochemical characterization of yeast alkylpurine DNA glycosylases | |
dc.type | dissertation | |
dc.contributor.committeeMember | Brandt Eichman | |
dc.contributor.committeeMember | Charles K. Singleton | |
dc.contributor.committeeMember | Neil Osheroff | |
dc.type.material | text | |
thesis.degree.name | PHD | |
thesis.degree.level | dissertation | |
thesis.degree.discipline | Biological Sciences | |
thesis.degree.grantor | Vanderbilt University | |
local.embargo.terms | 2014-03-04 | |
local.embargo.lift | 2014-03-04 | |
dc.contributor.committeeChair | Katherine L. Friedman | |