Environmental & Molecular Toxicology

Samuel Bennett

Asst. Professor/Sr. Res
Dept: EMT (1109 Ag Life Sciences Bldg)
Phone: 541-737-1798
Fax: 541-737-0497
bennetsa@onid.oregonstate.edu

Scientific Interests

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.

Selected Publications

Gafken, P.R., Doneanu, C.E., Bennett, S.E., and Barofsky, D.F.(2007) Comparison of ESI-MS interfaces for the analysis of UV-crosslinked peptide-nucleic acid complexes. J. Chromatogr. B 860, 145-152.

Bennett, S.E., and Kitner, J.  Characterization of the aldehyde reactive probe reaction with AP-sites in DNA: influence of AP-lyase on adduct stability. Nucleosides Nucleotides Nucleic Acids 25, 823-842.

Lari, S.U., Chen, C.Y., Vertéssy, B.G., Morré, J., and Bennett S.E.(2006)  Quantitative determination of uracil residues in Escherichia coli DNA: Contribution of ung, dug, and dut genes to uracil avoidance. DNA Repair 5, 1407-20. 

CHEN, C.-Y., MOSBAUGH, D.W., and BENNETT, S.E. (2005) Mutations at Arginine 276 Transform Human Uracil-DNA Glycosylase into a Single-stranded DNA-specific Uracil-DNA Glycosylase. DNA Repair (in press).

Ko, R., and BENNETT, S.E. (2005) Physical and Functional Interaction of Human Nuclear Uracil-DNA Glycosylase with Proliferating Cell Nuclear Antigen. DNA Repair 4(7):793-805.

DONEAU, C.E., GAFKEN, P.R., BENNETT, S.E., and BAROFSKY, D.F. (2004) Mass Spectrometry of UV-Cross-Linked Protein-Nucleic Acid Complexes: Identification of Amino Acid Residues in the Single-Stranded DNA-Binding Domain of Human Replication Protein A. Anal. Chem. 76, 5667-5676.

CHEN, C.-Y., MOSBAUGH, D.W., and BENNETT, S.E. (2004) Mutational Analysis of Arginine 276 in the Leucine-loop of human Uracil-DNA Glycosylase. J. Biol. Chem. 279, 48177-48188.

BENNETT, S.E., CHEN, C.-Y., and MOSBAUGH, D.W. (2004) Escherichia coli Nucleoside Diphosphate Kinase Does Not Act As A Uracil-Processing DNA Repair Nuclease. Proc. Natl. Acad. Sci. USA.101, 6391-6396.

BENNETT, S.E., SHROYER, M.J., SUNG, J.-S., and MOSBAUGH, D.W. (2002) Purification of Mitochondrial Uracil-DNA Glycosylase Using Ugi-Sepharose Affinity Chromatography. Methods Mol. Biol. 197, 211-225.

BENNETT, S.E., SUNG, J.-S., and MOSBAUGH, D.W. (2001) Fidelity of Uracil-initiated Base Excision DNA Repair in Mouse Embryonic Fibroblast Cell Extracts. J. Biol. Chem. 276, 42588-42600.

SHCHERBAKOVA, P.V., HALL, M.C., BENNETT, S.E., MARTIN, K.J., BUSHEL, P.R., AFSHARI, C.A., and KUNKEL, T.A. (2000) Increased Expression of Yeast MLH1 Inactivates Mismatch Repair. Mol. Cell. Biol. 21, 940-951.

SUNG, J.-S., BENNETT, S.E., and MOSBAUGH, D.W. (2000) Fidelity of Uracil-Initiated Base Excision DNA Repair in Escherichia coli Cell Extracts. J. Biol. Chem. 276, 2276-2285.

SANDERSON, R. J., BENNETT, S.E., SUNG, J.-S., and MOSBAUGH, D.W. (2000) Uracil-Initiated Base Excision DNA Repair Synthesis Fidelity in Human Colon Adenocarcinoma LoVo and Escherichia coli Cell Extracts. Prog. Nucleic Acids Res. Mol. Biol. 68, 165-188

MOSER, M.J., KAMATH-LOEB, A.S., JACOB, J.E., BENNETT, S.E., OSHIMA, J., and MONNAT, R.J. JR. (1999) WRN Helicase Expression in Werner Syndrome Cell Lines. Nucleic Acids Res. 28, 648-54

SHROYER, M.J.N., BENNETT, S.E., PUTNAM, C.D., TAINER, J.A., and MOSBAUGH, D.W. (1999) Mutation of an Active Site Residue in Escherichia coli Uracil-DNA Glycosylase: Effect on DNA-Binding, Uracil Inhibition and Catalysis. Biochemistry 38, 4834-45