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Structural Insights Into Dna Replication And Lesion Bypass By Y Family Dna Polymerases, Kevin N. Kirouac

Electronic Thesis and Dissertation Repository

Y family DNA polymerases are specialized enzymes for replication through sites of DNA damage in the genome. Although the DNA damage bypass activity of these enzymes is important for genome maintenance and integrity, it is also responsible for DNA mutagenesis due to the error-prone nature of the Y family. Understanding how these enzymes select incoming nucleotides during DNA replication will give insight into their role in cancer formation, aging, and evolution. This work attempts to mechanistically explain, primarily through X-ray crystallography and enzymatic activity assays, how Y family polymerases select incoming nucleotides in various DNA replication contexts. Initially, we sought …

Antimicrobial And Anticancer Activity Of Essential Oils From Guatemalan Medicinal Plants, Andrew B. Miller

Theses and Dissertations

Guatemalan medicinal plants were collected and screened for the presence of essential oils using steam distillation. Oil was found in 63 species from 24 families and was tested in tube dilution assays for activity against Escherichia coli, Staphylococcus aureus, Streptococcus mutans, Lactobacillus acidophilus and Candida albicans. Several essential oils were highly active with 20 instances of oils inhibiting the microbes at an MIC of 0.31 µl/ml. Oils were also tested against cancerous and established cell lines using a 15% (v/v) agar-media which was developed to improve essential oil solubility. Assays were performed against three cancer lines: …

Characterizing The Role Of Dna Repair Proteins In Telomere Length Regulation And Maintenance: Fanconi Anemia Complementation Group C Protein And 8-Oxoguanine Dna Glycosylase, David Beomjin Rhee

Doctoral Dissertations

Telomeres are the chromosome end structures consisting of telomere-associated proteins and short tandem repeat sequences, TTAGGG, in humans and mice. Telomeres prevent chromosome termini from being recognized as broken DNA ends. The structural integrity of DNA including telomeres is constantly threatened by a variety of DNA damaging agents on a daily basis. To counteract the constant threats from DNA damage, organisms have developed a number of DNA repair pathways to ensure that the integrity of genome remains intact. A number of DNA repair proteins localize to telomeres and contribute to telomere maintenance; however, it is still unclear as to what …

A Case Study On The Use Of Athletic Performance Strategies In An Elite Athlete’S Management Of Pancreatic Cancer, Brooke Elisabeth Harris

Boise State University Theses and Dissertations

In 2007, 11.7 million people in the United States were living with a cancer diagnosis. Specifically, 12 in every 100,000 Americans are diagnosed with pancreatic cancer each year. The five year survival rate of pancreatic cancer in the United States is only 5.6% (National Cancer Institute, 2007). In addition to traditional pharmacological treatments, physical activity has been increasingly used to help individuals successfully cope with cancer. One area that has not been studied extensively is the use of sport psychology techniques to help athletes cope with cancer. It is possible that these techniques, learned by elite athletes during their careers, …

Understanding Acquired Resistance To Lapatinib In Breast Cancer Cells, Jen-Te Tseng

Dissertations & Theses (Open Access)

Signaling through epidermal growth factor receptor (EGFR/ErbB) family members plays a very important role in regulating proliferation, development, and malignant transformation of mammary epithelial cells. ErbB family members are often over-expressed in human breast carcinomas. Lapatinib is an ErbB1 and ErbB2 tyrosine kinase inhibitor that has been shown to have anti-proliferative effects in breast and lung cancer cells. Cells treated with Lapatinib undergo G1 phase arrest, followed by apoptosis. Lapatinib has been approved for clinical use, though patients have developed resistance to the drug, as seen previously with other EGFR inhibitors. Moreover, the therapeutic efficacy varies significantly within the patient …

Functional Analysis Of Chromodomain Helicase Dna Binding Protein 2(Chd2) Mediated Genomic Stability, Sangeetha Rajagopalan

Doctoral Dissertations

Histone modifying enzymes and chromatin remodeling complexes play an important regulatory role in chromatin dynamics that dictate the interaction of regulatory factors involved in processes such as DNA replication, recombination, repair and transcription, with DNA template. The CHD (Chromodomain Helicase DNA Binding Protein) family of proteins is known to be involved in the regulation of gene expression, recombination and chromatin remodeling via their chromatin specific interactions and activities. Phenotypic analysis of the Chd2 mutant mouse model developed by our laboratory indicates that the Chd2 protein plays a critical role in tumor suppression as the heterozygous mutant mice develop spontaneous lymphomas. …

The Role Of Igf-1 And Notch Signaling In Thoracic Malignancies., Sandra Eliasz

Dissertations

Thoracic malignancies are one of the deadliest of all cancers, being the leading cause of cancer death in the Western world. Thoracic malignancies arise from different tissues; however the most common are of epithelial (commonly referred to as non-small cell lung cancer, or NSCLC), neuroendocrine (small cell lung cancer, or SCLC) and mesothelial origin (malignant mesothelioma, or MM). The DNA oncogenic virus Simian Virus 40 (SV40) has been shown to cooperate with environmental oncogenic fibers in the onset of MM. Insulin like growth factor-1 (IGF-1) signaling plays a central role in all thoracic malignancies and in the process of SV40-mediated …

Molecular Mechanisms Of Pressure-Stimulated Cancer Cell Signaling, Christina Downey

Wayne State University Dissertations

ABSTRACT

MOLECULAR MECHANISMS OF PRESSURE-STIMULATED CANCER CELL SIGNALING

by

CHRISTINA DOWNEY

June 2010

Advisor: Dr. Marc Basson, MD, PhD

Major: Cancer Biology

Degree: Doctor of Philosophy

Increased extracellular pressure stimulates cancer cell adhesion by a mechanism that is dependent upon beta-1-integrin activation, an intact cytoskeleton, and FAK and Src activation. By a different mechanism, increased extracellular pressure modulates cancer cell proliferation in a manner that is regulated by protein kinase C, but not Src or an intact cytoskeleton. Previous studies from our laboratory have shown that paxillin is a necessary mediator in the pathway by which pressure stimulates adhesion; however, …

Structural Investigation Of Atp-Utilizing Enzymes: Structures Involved In H+ Homeostasis And The Proliferation Of Hormone-Dependent Cancers, Zacariah Louis Hildenbrand

Open Access Theses & Dissertations

ATP is a multifunctional nucleotide considered to be the "molecular unit of currency" of intracellular energy transfer. ATP is utilized ubiquitously for the transport of chemical energy within the cell in addition to acting as a substrate in the regulation of many metabolic and signaling transduction pathways such as kinase-mediated signaling cascades. Interestingly, the functional mechanisms of many enzymes require the binding of ATP to trigger key structural and conformational changes that ultimately result in enzyme-directed catalysis. Two of the most omnipresent ATPases within the cell include the V-ATPase rotary proton pump and the Hsp90 protein-folding chaperone. Structural and biochemical …

Regulatory And Functional Aspects Of Foxo3a Transcription Factor And Their Implications In Prostate Cancer, Melissa Elise Dobson

Wayne State University Dissertations

The P13K/Akt pathway is a critical mediator of growth factor signaling involving many cellular functions. The deregulation of this pathway has been shown to be involved in the development of various cancers. One of the main targets of this pathway is FoxO3a, a transcription factor whose target genes are involved in important cellular processes such as apoptosis, cell cycle control, and glucose metabolism. FoxO3a is regulated by various post translational modifications including acetylation, ubiquitination and phosphorylation. The transcription factor is directly phosphorylated by Akt on 3 residues: Threonine 32, Serine 253 and Serine 315. Phosphorylation by Akt generates binding sites …