Thomas E. Wilson, M.D. Ph.D.
Assistant Professor
Campus Address:
Medical Science I M4214/0602
1301 Catherine Rd.
Ann Arbor, MI 48109-0602
Phone: 734/936-1887
wilsonte@umich.edu
Annual Report | Biography | Clinical Interests | Research Interests | Selected Publications
Departmental Annual Report
Dr. Wilson's
laboratory web-site:
http://tewlab.path.med.umich.edu/
Biography
Dr. Wilson received a B.S. in Biochemistry from the University of Wisconsin in 1987. He went on to study the health sciences, with an emphasis on molecular biology and neuroscience, at Washington University in St. Louis. He received his M.D. and Ph. D. in 1994. He continued at Washington University pursuing postgraduate clinical training in Laboratory Medicine, with an emphasis on molecular diagnostics, and research training in DNA repair as a Howard Hughes postdoctoral fellow in the laboratory of Dr. Michael Lieber. He joined the faculty at the University of Michigan as an Assistant Professor and Biological Sciences Scholar in 1999.
Clinical Interests
Research Interests
Mutagenesis, DNA repair, chromosomal dynamics
The goal of our laboratory is to gain insight into the molecular basis
of chromosomal rearrangement in cancer by systematically identifying both
enzymatic and structural components of the DNA double-strand break (DSB)
repair mechanisms and characterizing how these (and deficiencies therein)
interact to achieve the sequence of biochemical events resulting in repair
(or rearrangement). This is done primarily using novel assays developed
in the genetically tractable model organism Saccharomyces cerevisiae,
since it is now clear that the fundamental mechanisms of DSB repair are
preserved in all eukaryotes. First, a genetic approach termed suicide
deletion is being used to explore how a cell chooses between the two major
pathways of DSB repair, namely homologous recombination and nonhomologous
end-joining. Paradigms are in place to determine the mechanisms that signal
repair preference as a function of cell state, as well as the enzymes
involved in 5' resection, the committed step in recombination. Second,
we are continuing to identify and characterize the enzymes that process
damaged terminal bases and ligate DSB ends. Mammalian DNA polymerases
b and l are being used in chimeric and other structure-function analyses
to extend our previous findings regarding yeast Pol4, and hopefully to
predict the enzymes involved in mammalian DSB repair. Other enzymes being
studied are polynucleotide kinase, 5' and 3' nucleases, Rad50/Mre11, and
DNA ligase IV. Third, we are beginning to characterize in vivo the chromatin
complexes assembled during repair. Using carefully designed gene substrates
and DNA mapping technology, we hope to establish a methodological approach
to open this next frontier of DSB repair.
Selected Publications
Wilson TE, Grawunder U, Lieber MR. Yeast DNA ligase IV
mediates non-homologous DNA end joining. Nature 388: 495-498 (1997).
Wu XT, Wilson TE, Lieber MR. A role for FEN-1 in nonhomologous DNA end joining: the order of strand annealing and nucleolytic processing events. Proc Natl Acad Sci USA 96: 1303-1308 (1999).
Wilson TE, Lieber MR. Efficient processing of DNA ends during yeast nonhomologous end-joining: evidence for a DNA polymerase beta (POL4)-dependent pathway. J. Biol Chem; 274: 23599-609 (1999). This manuscript was communicated by Wilson TE, who acts as corresponding author.
Vance JR, Wilson TE. Uncoupling of 3' phosphatase and 5' kinase functions in budding yeast: Characterization of S. cerevisiae DNA 3' phosphatase (TPP1). J. Biol. Chem. 276: 15073-81 (2001).
Vance JR, Wilson TE. Repair of DNA strand breaks by the
overlapping functions of lesion-specific and non-specific DNA 3' phosphatases.
Mol Cell Biol. in press (2001).