Recent advances in understanding the molecular mechanisms of mutagenesis indicate that most mutations are dependent on the activity of translesion synthesis DNA polymerases. The impact of reducing the level of these polymerases on mutagenesis and...
The Y family of DNA polymerases in higher eukaryotes contains at least four members which are implicated in potentially error-prone replication through unrepaired damage in the genome. These proteins are encoded by the REV1, POLH, POLI, and POLK...
Unrepaired DNA damage poses a serious threat to the genetic stability of a replicating cell. One mechanism of tolerating this damage is translesion DNA synthesis (TLS), in which an accessory polymerase synthesizes DNA directly across from a damaged...
Drug resistance in microorganisms; Salmonella typhimurium
Salmonella enterica serovar Typhimurium is an enteric pathogen capable of infecting
a wide range of hosts. The manner in which this pathogen is able to interact with its
host is difficult to define, as is the case with most microbes. Through the...
Few previous studies have compared microbial communities in subterranean and surface environments. Chemical analyses used to characterize the surface and cave microbial environments indicated limited exchange between surface and subsurface waters....
This thesis begins by reviewing human N-acetyltransferases (Chapter I), then outlines experiments involving human hepatocytes and rat N-acetyltransferases (Chapters II-V). These experiments facilitated the development of a dissertation project...
Guanine-rich oligonucleotides (GROs) are being developed as a novel anticancer agents. GROs exhibit potent antiproliferative properties against several malignant cell lines and in established in vivo tumor models. In a recent Phase I clinical trial...
High-throughput sequencing has provided a myriad of genetic data for thousands of organisms. Computational analysis of one data type, expressed sequence tags (ESTs) yields insight into gene expression, alternative splicing, tissue specificity gene...
Hepatitis C virus--Research; Interferon--Therapeutic use; Adenosylmethionine
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the United States and is a huge burden on the US healthcare system. The FDA-approved traditional standard of care for HCV is pegylated interferon-alpha (lFNα) combined...
Ribosomal biogenesis failure may contribute to neurodegenerative diseases, while its excessive activation has been shown to drive tumor growth. As ribosomal production is initiated and regulated by the Pol1-mediated transcription of rRNA genes in...
Current high-throughput gene expression experiments have a straightforward design of examining
the gene expression of one group or condition relative to that of another. The data is typically
analyzed as if they represent strictly intracellular...
The inherited bone marrow failure syndromes (IBMFS) encompass a heterogeneous collection of rare disorders characterized by hematological abnormalities, generalized growth delays, and an increased incidence of malignant transformation. These...
N-acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4-aminobiphenyl (ASP). NAT1 catalyzes N-acetylation of arylamines as well as the 0-acetylation...
In the age of high-throughput molecular biology techniques, scientists have incorporated the methodology of in-situ hybridization to map spatial patterns of gene expression. In order to compare expression patterns within a common tissue structure,...
Pancreatic beta cells are extremely vulnerable to destruction by Reactive Oxygen Species (ROS). In type 1 diabetes and islet transplantation ROS are thought to be involved in the loss of beta cells. To test the role of antioxidant in islet...
Inflammatory bowel disease (IBD) is a chronic autoimmune disorder that is subdivided into Crohn's disease (CD), ulcerative colitis (UC), and indeterminate colitis (IC). Epidemiological studies have proven that genetic variation increases...
c-Myc dysregulation is one of the most common abnormalities found in human cancer. MicroRNAs (miRNAs) are functionally intertwined with the c-Myc network as multiple miRNAs are regulated by c-Myc, while others directly suppress c-Myc expression. In...
For more than a hundred million years, male plethodontid salamanders have
utilized non-volatile, proteinaceous courtship pheromones to regulate female mating
receptivity and promote mating success. These pheromones - which are delivered...
MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level by repressing translation or stimulating mRNA degradation. In this study, I tested the hypothesis that miRNAs are differentially expressed in antiestrogen-sensitive MCF-7...
Bcl-2 proteins are major regulators of cellular responses to various apoptotic stimuli. Among them, overexpression of the anti-apoptotic BcI-2 protein BcI-xL modulates organelle-specific apoptotic pathways. To understand the mechanisms by which...
