Nucleic Acids Research, Vol 26, Issue 12 2879-2885, Copyright © 1998 by Oxford University Press
JC Shen, MD Gray, J Oshima and LA Loeb
Werner syndrome is an inherited disease characterized by premature aging,
genetic instability and a high incidence of cancer. The wild type Werner
syndrome protein (WRN) has been demonstrated to exhibit DNA helicase
activity in vitro. Here we report further biochemical characterization of
the WRN helicase. The enzyme unwinds double- stranded DNA, translocating
3'-->5' on the enzyme-bound strand. Hydrolysis of dATP or ATP, and to a
lesser extent hydrolysis of dCTP or CTP, supports WRN-catalyzed
strand-displacement. K m values for ATP and dATP are 51 and 119 microM,
respectively, and 2.1 and 3.9 mM for CTP and dCTP, respectively.
Strand-displacement activity of WRN is stimulated by single-stranded
DNA-binding proteins (SSBs). Among the SSBs from Escherichia coli,
bacteriophage T4 and human, stimulation by human SSB (human replication
protein A, hRPA) is the most extensive and occurs with a stoichiometry
which suggests direct interaction with WRN. A deficit in the interaction of
WRN with hRPA may be associated with deletion mutations that occur at
elevated frequency in Werner syndrome cells.
ARTICLES
Characterization of Werner syndrome protein DNA helicase activity: directionality, substrate dependence and stimulation by replication protein A
Department of Pathology, University of Washington, Box 357705, Seattle, WA 98195-7705, USA.
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A. S. Kamath-Loeb, J.-C. Shen, L. A. Loeb, and M. Fry Werner Syndrome Protein. II. CHARACTERIZATION OF THE INTEGRAL 3' right-arrow 5' DNA EXONUCLEASE J. Biol. Chem., December 18, 1998; 273(51): 34145 - 34150. [Abstract] [Full Text] [PDF]
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R. M. Brosh Jr., A. Majumdar, S. Desai, I. D. Hickson, V. A. Bohr, and M. M. Seidman Unwinding of a DNA Triple Helix by the Werner and Bloom Syndrome Helicases J. Biol. Chem., January 26, 2001; 276(5): 3024 - 3030. [Abstract] [Full Text] [PDF]
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B. Li and L. Comai Requirements for the Nucleolytic Processing of DNA Ends by the Werner Syndrome Protein-Ku70/80 Complex J. Biol. Chem., March 23, 2001; 276(13): 9896 - 9902. [Abstract] [Full Text] [PDF]
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A. S. Kamath-Loeb, L. A. Loeb, E. Johansson, P. M. J. Burgers, and M. Fry Interactions between the Werner Syndrome Helicase and DNA Polymerase delta Specifically Facilitate Copying of Tetraplex and Hairpin Structures of the d(CGG)n Trinucleotide Repeat Sequence J. Biol. Chem., May 4, 2001; 276(19): 16439 - 16446. [Abstract] [Full Text] [PDF]
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R. M. Brosh Jr., P. Karmakar, J. A. Sommers, Q. Yang, X. W. Wang, E. A. Spillare, C. C. Harris, and V. A. Bohr p53 Modulates the Exonuclease Activity of Werner Syndrome Protein J. Biol. Chem., September 7, 2001; 276(37): 35093 - 35102. [Abstract] [Full Text] [PDF]
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P. L. Opresko, J.-P. Laine, R. M. Brosh Jr., M. M. Seidman, and V. A. Bohr Coordinate Action of the Helicase and 3' to 5' Exonuclease of Werner Syndrome Protein J. Biol. Chem., November 21, 2001; 276(48): 44677 - 44687. [Abstract] [Full Text] [PDF]
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G. Villani and N. Tanguy Le Gac Interactions of DNA Helicases with Damaged DNA: Possible Biological Consequences J. Biol. Chem., October 20, 2000; 275(43): 33185 - 33188. [Full Text] [PDF]
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H. Cohen and D. A. Sinclair Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase PNAS, March 13, 2001; 98(6): 3174 - 3179. [Abstract] [Full Text] [PDF]
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