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Samuel Bennett
Assistant Professor, Senior Research, Environmental and Molecular Toxicology
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RESEARCH:
We are interested in the molecular and biochemical mechanisms that maintain the genetic integrity of DNA during replication and in response to DNA damage. Many environmental chemicals are recognized as genotoxic agents because they cause DNA damage or interfere with DNA replication and/or transcription. Current research is aimed at understanding the enzymes involved in DNA repair pathways and in high fidelity DNA repair synthesis. We are specifically interested in repair mechanisms that eliminate uracil residues from DNA. Introduction of uracil residues into DNA has cytotoxic, mutagenic, and even lethal consequences. Moreover, deprivation, mutation, or altered regulation of specific uracil-DNA repair enzymes has been linked to increased mutation frequencies, chromosomal aberrations, and altered cell cycle regulation in human cell lines. Related research projects in the laboratory include quantitative determination of uracil residues in nuclear and mitochondrial DNA, and identification of factors that influence uracil accumulation, such as cell cycle, folate deficiency, environmental toxins, and deficient uracil-initiated base excision DNA repair. We also wish to learn more about the process of DNA repair in mitochondria. Little is known about mitochondrial uracil-DNA repair pathways. For example, what enzymes are involved, what is the DNA repair patch size, and what is the fidelity of mitochondrial DNA repair synthesis? The overall objective of our research is to understand the basic cellular mechanisms involved in mutation avoidance.
A second interest of the laboratory is the proteomics of secreted proteins in brain cells. In collaboration with the Mass Spectrometry Facility of the Environmental Health Sciences Center, we are investigating the secretory response of microglia cells to various activating stimuli, such as the organic pesticide rotenone, and tumor necrosis factor alpha. In addition, we are studying the secretory response of neurons to ischemic conditions.