Show simple item record

dc.contributor.author Kuschak, Theodore I. en_US
dc.date.accessioned 2007-05-18T19:57:08Z
dc.date.available 2007-05-18T19:57:08Z
dc.date.issued 2000-07-01T00:00:00Z en_US
dc.identifier.uri http://hdl.handle.net/1993/1748
dc.description.abstract c-Myc deregulation has been shown to generate locus-specific chromosomal and extrachromosomal gene amplification, as well as karyotypic instability. My studies focused on c-Myc-dependent amplification of a new c-Myc amplification target, the 'ribonucleotide reductase R2' gene. Using a mouse Pre-B cell line we showed chromosomal and extrachromosomal amplification and rearrangement of the 'R2' gene locus within 72 hours of transient and inducible c-Myc deregulation. We further showed that the initiation of c-Myc-dependent R2 instability occurs as early as 24 hours of transient c-Myc deregulation. Previous studies have demonstrated gene amplification using cell cycle inhibiting drugs, resulting in locus-specific gene amplification within 5-22 replication cycles. My study is novel in that it uses an inducible system to study initiation of c-Myc-dep ndent 'R2' amplification. The results of this work suggest that the c-Myc-dependent initiation of amplification of 'R2' is replication-driven. This does not exclude subsequent gene amplification through other mechanisms. To study c-Myc-dependent extrachromosomal gene amplification, we developed two methods for the analysis of extrachromosomal DNA amplicons. These methods include fluorescent 'in situ' hybridization to characterize the genes found in the total population of purified extrachromosomal DNA and the specific isolation of histone-bound extrachromosomal DNA, which is associated with active genes. en_US
dc.format.extent 18676680 bytes
dc.format.extent 184 bytes
dc.format.mimetype application/pdf
dc.format.mimetype text/plain
dc.language en en_US
dc.language.iso en_US
dc.title c-Myc dependent genomic instability of the ribonucleotide reductase R2 gene en_US
dc.degree.discipline Microbiology en_US
dc.degree.level Doctor of Philosophy (Ph.D.) en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

View Statistics