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Author Nosala, Christopher, author.
Title Epigenetic regulation of developmentally regulated B cell gene silencing and specificity of dCK TM for L-FMAU : a new reporter gene for positron emission tomography / by Christopher Nosala.
Published [Northridge, California] : California State University, Northridge, 2012.

 Electronic Book  QH51 .Z95 2012 N67eb    ONLINE
Description 1 online resource (iv, 120 pages)
Content Type text
Format online resource
File Characteristics text file PDF
Thesis M.S. California State University, Northridge 2012.
Bibliography Includes bibliographical references (pages 114-120).
Note Description based on online resource; title from PDF title page (viewed on August 27, 2012).
Summary Two studies were undertaken that investigate the implications of small biochemical alterations in living systems. First, epigenetic mechanisms have been shown to control gene expression and can permanently silence a gene. We investigate the role of the epigenetic mechanisms DNA methylation and histone deacetylation in the stage specific silencing of the gene VpreB. This gene must be expressed and extinguished at specific stages for the healthy development of the B cell. Reactivation of VpreB gene expression was observed after inhibiting epigenetic mechanisms in Ramos cells in which VpreB is permanently silenced. Furthermore, no DNA methylation was found within the promoter region of VpreB in Nalm6 cells in which VpreB is expressed. Therefore, DNA methylation and histone deacetylation was observed to be correlated with the onset of VpreB silencing in cell lines. Next, the author explores the effects on substrate specificity of single point mutations within the active site of the enzyme deoxycytidine kinase (dCK). dCK is the rate limiting step for the salvage of several nucleosides as an alternate to de novo nucleotide synthesis. Furthermore, dCK is responsible for the activation of several chemotherapeutic nucleoside analog prodrugs such as gemcitibine. By making three mutations (A100V, R104M, D133A) within the active site of dCK, we were able to successfully increase dCK's specificity for the thymidine analog 2'-deoxy-2'-5-methyl-1-[beta]-L-arabinofuranosyluracil (L-FMAU) that can be used for positron emission tomography (PET), a medical imaging modality. The author also confirmed previous results that the three mutations can broaden dCK's specificity for thymidine. These results indicate that dCK's activity can be easily manipulated to increase specificity and turnover for thymidine analogs including L-FMAU.
Subject Epigenetics.
Local Subject Dissertations, Academic -- CSUN -- Biology.
OCLC number 849972475