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Personal profile

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.

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Projects 1991 2023

Nitrosamines
DNA Adducts
Tobacco
Oligodeoxyribonucleotides
Smoke
DNA Repair
Carcinogens
DNA Adducts
Tobacco
Lung Neoplasms

Chemistry of mutagenesis

Spratt, T.

National Institutes of Health

8/1/057/31/06

Project: Research project

Mutagenesis
DNA
DNA-Directed DNA Polymerase
Carcinogens
Nucleotides
Mutagenesis
DNA
Carcinogens
DNA-Directed DNA Polymerase
DNA Polymerase I
Cysteine
Guanine
Protonation
DNA
Substrates

Research Output 1983 2017

  • 1588 Citations
  • 25 h-Index
  • 61 Article
  • 2 Comment/debate
  • 1 Letter
  • 1 Review article

Active Site Interactions Impact Phosphoryl Transfer during Replication of Damaged and Undamaged DNA by Escherichia coli DNA Polymerase i

Prakasha Gowda, A. S. & Spratt, T., Nov 20 2017, In : Chemical Research in Toxicology. 30, 11, p. 2033-2043 11 p.

Research output: Contribution to journalArticle

Guanine
DNA-Directed DNA Polymerase
Escherichia coli
Catalytic Domain
DNA
3 Citations (Scopus)

Honokiol Inhibits DNA Polymerases β and λ and Increases Bleomycin Sensitivity of Human Cancer Cells

Gowda, A. S. P., Suo, Z. & Spratt, T., Feb 20 2017, In : Chemical Research in Toxicology. 30, 2, p. 715-725 11 p.

Research output: Contribution to journalArticle

Bleomycin
DNA-Directed DNA Polymerase
temozolomide
Cells
Repair
1 Citations (Scopus)
Sulfolobus solfataricus
DNA Polymerase beta
Deoxyguanosine
Benzo(a)pyrene
DNA-Directed DNA Polymerase
2 Citations (Scopus)

N2-Substituted 2′-Deoxyguanosine Triphosphate Derivatives as Selective Substrates for Human DNA Polymerase κ

Gowda, A. S. P., Lee, M. & Spratt, T., Jan 1 2017, In : Angewandte Chemie - International Edition. 56, 10, p. 2628-2631 4 p.

Research output: Contribution to journalArticle

DNA-Directed DNA Polymerase
DNA
Derivatives
Substrates
Azides
6 Citations (Scopus)

DNA Polymerases η and ζ Combine to Bypass O2-[4-(3-Pyridyl)-4-oxobutyl]thymine, a DNA Adduct Formed from Tobacco Carcinogens

Prakasha Gowda, A. S. & Spratt, T., Mar 21 2016, In : Chemical Research in Toxicology. 29, 3, p. 303-316 14 p.

Research output: Contribution to journalArticle

N'-nitrosonornicotine
Thymine
Tobacco
DNA Adducts
DNA-Directed DNA Polymerase