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A Critical Review Of Telomerase Biology And Model Systems For The Study Of Telomerase, Jeremy Charles Aisenberg Jan 2006

A Critical Review Of Telomerase Biology And Model Systems For The Study Of Telomerase, Jeremy Charles Aisenberg

Theses and Dissertations

The study of telomere and telomerase biology holds substantial promise in uncovering the molecular process of aging and the treatment of cancers. Studies have shown that telomere shortening is directly linked to cellular aging and that telomerase expression is found in over 85% of human cancers, including 95% of all advanced malignancies. Development of effective model systems to elucidate the molecular mechanisms underlying the role of telomeres and telomerase in the processes aging and cancer is of particular importance. While inbred strains of mice have provided a wealth of information for a variety of pathways and diseases, the mouse model …


Degenerate Oligonucleotide Primed-Pcr: Thermalcycling Modifications And Comparison Studies, Denise N. Rodier Jan 2006

Degenerate Oligonucleotide Primed-Pcr: Thermalcycling Modifications And Comparison Studies, Denise N. Rodier

Theses and Dissertations

Degenerate Oligonucleotide Primed-PCR (DOP-PCR) can potentially enhance analysis of low copy number DNA samples. Theoretically, this procedure replicates fragments of the genome that can then be used for downstream multiplex STR analysis. The objective of this study is to optimize DOP-PCR by examining ramplelongation times and cycle numbers in the non-specific amplification portion of DOP-PCR, and by modifying the degenerate primer. Additionally, other methods such as Multiple Displacement Amplification (MDA) and Low Copy Number PCR (LCN PCR) were examined for their ability to create accurate DNA profiles from low DNA input amounts. Increasing the ramplelongation times showed no effect on …


The Role Of Dna Methylation And Methyl Binding Domain Protein 2 In The Regulation Of Human Embryonic And Fetal Beta Type Globin Genes, Jeremy William Rupon Jan 2006

The Role Of Dna Methylation And Methyl Binding Domain Protein 2 In The Regulation Of Human Embryonic And Fetal Beta Type Globin Genes, Jeremy William Rupon

Theses and Dissertations

The genes of the human β-globin locus are located on chromosome 11 in the order of their expression during development: 5' ε, γ, β 3'. During development, silencing of the 5' gene occurs with activation of the immediate 3' gene. This process occurs twice and is termed hemoglobin switching. The exact mechanism(s) of this process have not been fully described. Herein, we describe a role for DNA methylation and methyl binding domain protein 2 in the transcriptional regulation of the human embryonic and fetal beta type globin genes. Adult mice containing the entire human β-globin locus as a yeast artificial …


Atm-Dependent Erk Signaling In Response To Dna Double Strand Breaks, Ashraf Khalil Jan 2006

Atm-Dependent Erk Signaling In Response To Dna Double Strand Breaks, Ashraf Khalil

Theses and Dissertations

Ionizing radiation (IR) triggers many signaling pathways stemming from DNA damage, and, independently, from extra-nuclear events. To generate radio-mimetic DNA double-strand breaks (DSBs) without and minimizing the effects on extra-nuclear radiation targets, human (p53+) glioma and carcinoma cells containing bromodeoxyuridine (BrdU)- substituted DNA were treated with Hoechst 33258 followed by long wave-length UV (UV-A) (BrdU photolysis). BrdU photolysis resulted in well-controlled, dose-dependent generation of DSBs equivalent to 0.2 - 20 Gy of IR, as detected by pulse-field gel electrophoresis, accompanied by dose-dependent H2AX phosphorylation at ser-139 and ATM phosphorylation at ser-1981, indicating ATM activation. Furthermore, BrdU photolysis increased phosphorylation of …