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dc.contributor.advisorWinston, Fred Marshall
dc.contributor.authorLoeliger, Erin Michelle
dc.date.accessioned2014-06-06T15:55:35Z
dc.date.issued2014-06-06
dc.date.submitted2014
dc.identifier.citationLoeliger, Erin Michelle. 2014. Structure-Function Analysis of the Conserved Histone Chaperone Spt6. Doctoral dissertation, Harvard University.en_US
dc.identifier.otherhttp://dissertations.umi.com/gsas.harvard:11369en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12274103
dc.description.abstractChromatin structure is crucial to regulate access to the genome for processes such as a transcription, recombination, DNA repair, and DNA replication. Spt6, a key factor involved in regulating chromatin structure, is conserved throughout eukaryotes. Spt6 has been shown to function in many aspects of gene expression, including nucleosome assembly, transcription initiation and elongation, and mRNA processing and export. In addition, Spt6 has several conserved domains; however, little is known about their functions. I have performed a structure-function analysis of Spt6 using three separate approaches. First, I employed a random insertion mutagenesis that has identified sixty-seven mutants. While these mutants did not provide information regarding known domains, some have phenotypes that may prove useful for future study. Second, in a collaborative project with Romier lab, I studied the functional roles of the Spt6 SH2 domains. I have shown that deletion of the region of Spt6 encoding the SH2 domains causes severe mutant phenotypes without affecting Spt6 protein levels, demonstrating the importance of the SH2 domains of Spt6. Third, in an additional collaboration with the Romier lab, I showed that mutations that alter the region of Spt6 that interacts with the conserved transcription factor Spn1 impair Spt6 functions in vivo. Overall, this multi-pronged structure-function analysis of Spt6 has provided new insights into the tandem SH2 domains of Spt6, the Spt6-Spn1 interaction, and the uses and limitations of insertion mutagenesis. In addition, I have attempted to explore a possible role for Spt6 in transcription-associated mutagenesis. After employing several types of in vivo assays, I conclude that a possible role for Spt6 in transcription-associated mutagenesis is uncertain, as the results (with respect to a role for Spt6) reproducibly vary depending on the assay used. Thus, understanding this aspect of Spt6 biology awaits better assays and understanding of transcription-associated mutagenesis. Overall, the work in this dissertation will serve to further elucidate the mechanisms of Spt6 in chromatin regulation, transcription, and DNA damage repair.en_US
dc.language.isoen_USen_US
dash.licenseLAA
dc.subjectGeneticsen_US
dc.subjectChromatinen_US
dc.subjectGeneticsen_US
dc.subjectHistone Chaperoneen_US
dc.subjectSpt6en_US
dc.subjectTranscriptionen_US
dc.subjectYeasten_US
dc.titleStructure-Function Analysis of the Conserved Histone Chaperone Spt6en_US
dc.typeThesis or Dissertationen_US
dash.depositing.authorLoeliger, Erin Michelle
dc.date.available2014-06-06T15:55:35Z
thesis.degree.date2014en_US
thesis.degree.disciplineGenetics and Genomicsen_US
thesis.degree.grantorHarvard Universityen_US
thesis.degree.leveldoctoralen_US
thesis.degree.namePh.D.en_US
dc.contributor.committeeMemberMoazed, Daneshen_US
dc.contributor.committeeMemberDymecki, Susanen_US
dc.contributor.committeeMemberLarschan, Ericaen_US
dash.contributor.affiliatedLoeliger, Erin


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