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Thomas Jefferson University - John M Pascal, PhD
John M Pascal, PhD

Biochemistry & Molecular Biology
Thomas Jefferson University
Jefferson Medical College
Assistant Professor
Mailing Address
233 South 10th Street, BLSB 804
Philadelphia, Pennsylvania 19107
United States
Contact Information
Phone: 215-503-4596
Fax: 215-923-2117
John.Pascal@mail.jci.tju.edu
Qualifications
Ph.D., University of Texas at Austin, 2000
Expertise and Research Interests
We study protein structure and function to understand how cells replicate and repair DNA, and how the integrity of the genome is preserved during these processes. A 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, biochemical tools, and cell biological approaches to assay protein structure and function.
Keywords
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; NAD metabolism; ADP ribosylation reactions
Publications
  • Steffen JD, Pascal JM. (2013) New players to the field of ADP-ribosylation make the final cut. EMBO J. 32, 205-7.
  • Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello MA, Dean JL, Liu F, Planck JL, Ravindranathan P, Chinnaiyan AM, McCue P, Gomella LG, Raj GV, Dicker AP, Brody JR, Pascal JM, Centenera MM, Butler LM, Tilley WD, Feng FY, Knudsen KE. (2012) Dual roles of PARP-1 promote cancer growth and progression. Cancer Discovery 2, 1134-49.
  • Zhang M, Pascal JM, Schumann M, Armen RS, Zhang JF. (2012) Identification of the functional binding pocket for compounds targeting small-conductance Ca²z-activated potassium channels. Nat Commun 3, 1021.
  • Langelier MF, Planck JL, Roy S & Pascal JM (2012) Structural basis for DNA-dependent poly(ADP-ribosyl)ation by human PARP-1. Science 336, 728-32.
  • Liu C, Sanders JM, Pascal JM & Hou YM. (2012) Adaptation to tRNA acceptor stem structure by flexible adjustment in the catalytic domain of class I tRNA synthetases. RNA 18:213-21.
  • Zhang M, Abrams C, Wang L, Gizzi A, He L, Lin R, Chen Y, Loll PJ, Pascal JM & Zhang J-f. (2012) Structural basis for calmodulin as a dynamic calcium sensor. Structure 20, 911-23.
  • Chan TO, Pascal JM, Armen RS, Rodeck U. (2012) Autoregulation of kinase dephosphorylation by ATP binding in AGC protein kinases. Cell Cycle 11:475-8.
  • Pascal JM (2012) DNA Ligases: structures. Encyclopedia of Biological Chemistry 2nd Edition (W.J. Lennartz and M.D. Lane, eds.), Elsevier, Oxford.
  • Chan TO, Zhang J, Rodeck U, Pascal JM, Armen RS, Spring M, Dumitru CD, Myers V, Li X, Cheung JY & Feldman AM. (2011) Resistance of Akt kinases to dephosphorylation through ATP-dependent conformational plasticity. PNAS 108, E1120-7.
  • Langelier M-F, Planck JL, Servent KM & Pascal JM. (2011) Purification of human PARP-1 and PARP-1 domains from E. coli for structural and biochemical analysis. Methods in Molecular Biology 780: 209-26.
  • Langelier M-F, Planck JL, Roy S & Pascal JM (2011) Crystal structures of poly(ADP-ribose) polymerase-1 (PARP-1) zinc fingers bound to DNA: structural and functional insights into DNA-dependent PARP-1 activity. Journal of Biological Chemistry 286, 10690-701.
  • Langelier M-F, Ruhl DD, Planck JL, Kraus WL & Pascal JM (2010) The Zn3 domain of human poly(ADP-ribose) polymerase-1 (PARP-1) functions in both DNA-dependent poly(ADP-ribose) synthesis activity and chromatin compaction. Journal of Biological Chemistry 285, 18877-87.
  • 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.

Individual Expertise profile of John M Pascal, PhD, Copyright © John M Pascal, PhD.
Last Updated by John Pascal, PhD : Monday, July 2, 2012 11:15:46 AM



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