DNA damage, if not repaired, can become a mutation. Mutation
accumulation is associated with initiation and progression of tumorigenesis. DNA
mismatch repair (MMR) is required for maintaining genetic stability by repairing
replication errors. Biochemical studies have shown that MMR also recognizes
mismatch-causing DNA lesions, suggesting the role of MMR in...
Intracellular dNTP pool sizes are highly asymmetric, with dGTP usually comprising 5 to 10% of the sum of the dNTP pools. The work presented in this dissertation addresses the question of whether the underrepresentation of dGTP is related to its potential to be oxidized by reactive oxygen species. 8-oxo-guanine is...
PCR-based codon-specific random mutagenesis and site-specific mutagenesis were performed to construct a library of 18 amino acid changes at Arg276 in the conserved leucine-loop of the core catalytic domain of human uracil-DNA glycosylase (UNG). Each Arg276 mutant was then overproduced in E. coli cells and purified to apparent homogeneity by...
In recent years, the methyl erythritol phosphate (MEP) pathway to isoprenoids has been the subject of intensive research. The interest is because isoprenoids have important roles in many cellular processes essential for the survival of several pathogenic organisms, making the inhibition of this pathway an attractive target for the drug...
Mitotic recombination is a common autosomal mutation in mammalian cells involving crossover events between homologous chromosomes. This process can convert a cell with a heterozygous deficiency to one with a homozygous deficiency, and thus often represents the second step in tumor suppressor gene inactivation. In this study I examined the...
The multistage model of carcinogenesis states that an accumulation of mutations in genes that are important for maintaining cellular homeostasis may lead to cancer. A specific type of mutation observed in particular types of cancer is the CC-->TT mutation found in the TP53 gene of patients with basal or squamous...