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Thomas Jefferson University - John M Pascal, Ph.D.
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Expertise and Research Interests
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We study protein structure to understand how cells replicate and repair DNA, and how the integrity of the genome is preserved in these processes. Our major objective is to determine the three-dimensional structure of proteins to visualize how their architecture and design are related to their functions in the cell. We are particularly interested in the proteins that detect and respond to breaks in the structure of DNA, a common and potentially lethal form of DNA damage. X-ray crystallography is our primary tool for determining the structures of proteins and protein-DNA complexes. We also use other biophysical techniques and biochemical tools to assay protein structure and function.
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Keywords
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Structural cell biology; protein structure and function; macromolecular x-ray crystallography; DNA damage detection and repair; DNA replication; chromosomal metabolism and genome maintenance; biochemistry; biophysics; poly(ADP-ribose) polymerases (PARPs); DNA ligases
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Publications
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- Song W, Pascal JM, Ellenberger T, Tomkinson AE (2009) The DNA binding domain of human DNA ligase I interacts with both nicked DNA and the DNA sliding clamps, PCNA and hRad9-hRad1-hHus1. DNA Repair 8, 912-9.
- Langelier M-F, Servent KM, Rogers EE & Pascal JM (2008) A third zinc binding domain in Poly(ADP-ribose) polymerase 1 coordinates DNA-dependent enzyme activation. Journal of Biological Chemistry 283, 4105-14.
- Pascal JM. (2008) DNA and RNA ligases: structural variations and shared mechanisms. Current Opinion in Structural Biology 18, 96-105.
- Pascal JM, Tsodikov OT, Hura G, Song W, Cotner EA, Classen S, Tomkinson AE, Tainer JA & Ellenberger T. (2006) A flexible interface between DNA ligase and a heterotrimeric sliding clamp supports conformational switching and efficient ligation of DNA. Molecular Cell 24, 279-291.
- Pascal JM & Ellenberger T. (2006) RNA ligase does the AMP shuffle. Nature Structure and Molecular Biology 13, 950-951.
- Tomkinson AE, Vijayakumar S, Pascal JM & Ellenberger T. (2006) DNA Ligases: structure, reaction mechanism and function. Chemical Reviews 106, 687-99.
- Xie C, Pascal J, Vijayakumar S, Wilson GM, Ellenberger T & Tomkinson AE. (2006) Human DNA ligases I, III, and IV: purification and new specific assays for these enzymes. Methods in Enzymology 409, 39-52.
- Pascal JM, O'Brien PJ, Tomkinson AE & Ellenberger T. (2004) Human DNA ligase I completely encircles and partially unwinds nicked DNA. Nature 432, 473-8.
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Individual Expertise profile of
John M Pascal, Ph.D., Copyright © John M Pascal, Ph.D..
Last Updated
by John Pascal, Ph.D. : Thursday, September 10, 2009 9:19:42 AM
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