Timothy M. Lohman, Ph.D.

Marvin A. Brennecke Professor of Biophysics
Biochemistry and Molecular Biophysics

Computational and Molecular Biophysics Program
Biochemistry Program

  • 314-362-4393

  • 314-362-4394

  • 314-362-7183

  • 8231

  • 2801 North Building

  • lohman@biochem.wustl.edu

  • http://biochem.wustl.edu/faculty/faculty/timothy-lohman

  • DNA recombination, DNA replication, fluorescence, molecular motors, single molecules, thermodynamics

  • Mechanisms of DNA helicases/translocases and SSB proteins

Research Abstract:

Our research focuses on obtaining a molecular understanding of the factors that affect the stability and specificity of protein-nucleic acid complexes, as well as their mechanisms of interaction. We are investigating the mechanisms by which duplex DNA is unwound catalytically by a class of motor proteins, called helicases. The unwinding of duplex DNA to form single stranded (ss) DNA is a prerequisite for replication, recombination and repair and this process is catalyzed by DNA helicases, which are ss DNA-stimulated ATPases. These enzymes are ubiquitous and central to all aspects of DNA metabolism. We are investigating several helicases, including E. coli Rep, E. coli UvrD (also known as Helicase II) and E. coli RecBCD, which are involved in DNA replication, repair, and recombination, respectively. Our goal is to understand the mechanism of helicase-catalyzed DNA unwinding and protein translocation along DNA and the role of ATP in these processes. We use thermodynamic, pre-steady state transient kinetic (fluorescence stopped-flow and chemical quenched-flow), single molecule fluorescence (TIRF), structural and molecular biological approaches to investigate these problems.

We are also investigating two single stranded DNA binding proteins, the E. coli SSB protein and the eukaryotic heterotrimeric RPA protein, which bind selectively to ss-DNA and facilitate DNA unwinding by the helicases. The binding of SSB to ss DNA is quite complex, since it binds to ss DNA in a number of different modes which may function selectively in replication, recombination and repair. Using fluorescence and isothermal titration calorimetry, we are investigating the molecular interactions that stabilize the SSB-ss-DNA complexes, the factors that influence the distribution of binding modes as well as the different cooperative behavior in each mode.

Selected Publications:

Lohman TM, Tomko EJ and Wu CG. Non-hexameric DNA helicases and translocases: mechanisms and regulation. Nature Reviews Molecular Cell Biology 2008 9: 391-401. Wu CG and Lohman TM. Influence of DNA End Structure on the Mechanism of Initiation of DNA Unwinding by the E. coli RecBCD and RecBC Helicases. J. Mol. Biol. 2008 382: 312-326. Antony E, Tomko EJ, Xiao Q. Krejci L, LoLohman TM, Tomko EJ and Wu CG. Non-hexameric DNA helicases and translocases: mechanisms and regulation. Nature Reviews Molecular Cell Biology 2008 9: 391-401.

Wu CG and Lohman TM. Influence of DNA End Structure on the Mechanism of Initiation of DNA Unwinding by the E. coli RecBCD and RecBC Helicases. J. Mol. Biol. 2008 382: 312-326.

Antony E, Tomko EJ, Xiao Q. Krejci L, Lohman TM and Ellenberger T. Srs2 Disassembles Rad51 Filaments by a Protein-Protein Interaction Triggering ATP Turnover and Dissociation of Rad51 from DNA. Molecular Cell 2009 35: 105-115.

Roy R, Kozlov AG, Lohman TM and Ha T. SSB diffusion on single stranded DNA stimulates RecA filament formation. Nature 2009 461: 1092-1097.

Kozlov AG, Cox MM and Lohman TM. Regulation of single stranded DNA binding by the C-termini of E. coli SSB Protein. J. Biological Chemistry 2010 285: 17246-17252.man TM and Ellenberger T. Srs2 Disassembles Rad51 Filaments by a Protein-Protein Interaction Triggering ATP Turnover and Dissociation of Rad51 from DNA. Molecular Cell 2009 35: 105-115. Roy R, Kozlov AG, Lohman TM and Ha T. SSB diffusion on single stranded DNA stimulates RecA filament formation. Nature 2009 461: 1092-1097. Kozlov AG, Cox MM and Lohman TM. Regulation of single stranded DNA binding by the C-termini of E. coli SSB Protein. J. Biological Chemistry 2010 285: 17246-17252.

Last Updated: 4/3/2017 3:17:52 PM

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