Researcher Profile

Researcher Profile

Thomas Spratt, PhD

Thomas Spratt, PhD

Professor, Department of Biochemistry and Molecular Biology
Scientific Program:Mechanisms of Carcinogenesis
tes13@psu.edu
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Research Interests

Dr. Thomas Spratt's research has focused on the elucidation of mechanisms of DNA damage, repair and mutagenesis. The Spratt lab uses a multidisciplinary approach including organic synthesis, steady-state and transient state kinetics, protein engineering, cell biology, mass spectrometry and next-generation sequencing.

The Spratt lab has made contributions in elucidating mechanisms of tobacco carcinogenesis. They have identified repair pathways and mutagenesis mechanisms of specific DNA adducts produced from tobacco smoke.

The Spratt Lab uses a chemical biology approach, in which modified nucleotides are designed and synthesized to elucidate specific aspects of the active site chemistry of DNA repair proteins and polymerases. In early work, the mechanism of action of O6-alkylguanine –DNA alkyltransferase, a critical DNA repair protein, was examined. More recently, critical protein-DNA and DNA-DNA interactions during the replication of undamaged and carcinogen-damage DNA have been identified.

Current research involves designing polymerase-specific substrates to probe the multi-faceted roles of translesion DNA polymerases in vivo.

  • DNA
  • DNA-Directed DNA Polymerase
  • Tobacco
  • Nitrosamines
  • Guanine
  • Base Pairing
  • Proteins
  • Carcinogens
  • Escherichia coli
  • DNA Polymerase I
  • DNA Adducts
  • Neoplasms

Recent Publications

2017

Prakasha Gowda, AS & Spratt, T 2017, 'Active Site Interactions Impact Phosphoryl Transfer during Replication of Damaged and Undamaged DNA by Escherichia coli DNA Polymerase i' Chemical Research in Toxicology, vol. 30, no. 11, pp. 2033-2043. https://doi.org/10.1021/acs.chemrestox.7b00257
Gowda, ASP, Suo, Z & Spratt, T 2017, 'Honokiol Inhibits DNA Polymerases β and λ and Increases Bleomycin Sensitivity of Human Cancer Cells', Chemical Research in Toxicology, vol. 30, no. 2, pp. 715-725. https://doi.org/10.1021/acs.chemrestox.6b00451
Gowda, ASP, Krzeminski, J, Amin, S, Suo, Z & Spratt, T 2017, 'Mutagenic Replication of N2-Deoxyguanosine Benzo[a]pyrene Adducts by Escherichia coli DNA Polymerase i and Sulfolobus solfataricus DNA Polymerase IV', Chemical Research in Toxicology, vol. 30, no. 5, pp. 1168-1176. https://doi.org/10.1021/acs.chemrestox.6b00466
Gowda, ASP, Lee, M & Spratt, T 2017, 'N2-Substituted 2′-Deoxyguanosine Triphosphate Derivatives as Selective Substrates for Human DNA Polymerase κ', Angewandte Chemie - International Edition, vol. 56, no. 10, pp. 2628-2631. https://doi.org/10.1002/anie.201611607

2016

Gowda, ASP & Spratt, T 2016, 'DNA Polymerase ν Rapidly Bypasses O6-Methyl-dG but Not O6-[4-(3-Pyridyl)-4-oxobutyl-dG and O2-Alkyl-dTs', Chemical Research in Toxicology, vol. 29, no. 11, pp. 1894-1900. https://doi.org/10.1021/acs.chemrestox.6b00318
Prakasha Gowda, AS & Spratt, T 2016, 'DNA Polymerases η and ζ Combine to Bypass O2-[4-(3-Pyridyl)-4-oxobutyl]thymine, a DNA Adduct Formed from Tobacco Carcinogens', Chemical Research in Toxicology, vol. 29, no. 3, pp. 303-316. https://doi.org/10.1021/acs.chemrestox.5b00468

2015

Gowda, ASP, Moldovan, G-L & Spratt, T 2015, 'Human DNA polymerase ν catalyzes correct and incorrect DNA synthesis with high catalytic efficiency', Journal of Biological Chemistry, vol. 290, no. 26, pp. 16292-16303. https://doi.org/10.1074/jbc.M115.653287
Weerasooriya, S, Jasti, VP, Bose, A, Spratt, T & Basu, AK 2015, 'Roles of translesion synthesis DNA polymerases in the potent mutagenicity of tobacco-specific nitrosamine-derived O2-alkylthymidines in human cells', DNA Repair, vol. 35, pp. 63-70. https://doi.org/10.1016/j.dnarep.2015.09.023

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