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J. Biol. Chem., Vol. 277, Issue 43, 41110-41119, October 25, 2002
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,,§,,
From the Werner syndrome is a human premature aging
disorder displaying cellular defects associated with telomere
maintenance including genomic instability, premature senescence, and
accelerated telomere erosion. The yeast homologue of the Werner protein
(WRN), Sgs1, is required for recombination-mediated lengthening of
telomeres in telomerase-deficient cells. In human cells, we report that WRN co-localizes and physically interacts with the critical telomere maintenance protein TRF2. This interaction is mediated by the RecQ
conserved C-terminal region of WRN. In vitro, TRF2
demonstrates high affinity for WRN and for another RecQ family member,
the Bloom syndrome protein (BLM). TRF2 interaction with either WRN or
BLM results in a notable stimulation of their helicase activities. Furthermore, the WRN and BLM helicases, partnered with replication protein A, actively unwind long telomeric duplex regions that are
pre-bound by TRF2. These results suggest that TRF2 functions with WRN, and possibly BLM, in a common pathway at telomeric ends.
Laboratory of Molecular Gerontology, NIA,
National Institutes of Health, Baltimore, Maryland 21224, the § Institut de Genetique et de Biologie Moleculaire et
Cellulaire, CNRS/INSERM/Universite Louis Pasteur, B.P. 163, 67404 Illkirch Cedex, France, and ¶ The Imperial Cancer Research Fund
Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital,
Oxford University, Oxford OX3 9DS, United Kingdom
To whom correspondence should be addressed: Laboratory of
Molecular Gerontology, NIA, National Institutes of Health, 5600 Nathan
Shock Dr., Baltimore, MD 21224. Tel.: 410-558-8162; Fax: 410-558-8157;
E-mail: vbohr@nih.gov.
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C. von Kobbe, J. A. Harrigan, A. May, P. L. Opresko, L. Dawut, W.-H. Cheng, and V. A. Bohr Central Role for the Werner Syndrome Protein/Poly(ADP-Ribose) Polymerase 1 Complex in the Poly(ADP-Ribosyl)ation Pathway after DNA Damage Mol. Cell. Biol., December 1, 2003; 23(23): 8601 - 8613. [Abstract] [Full Text] [PDF]
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H. Plchova, F. Hartung, and H. Puchta Biochemical Characterization of an Exonuclease from Arabidopsis thaliana Reveals Similarities to the DNA Exonuclease of the Human Werner Syndrome Protein J. Biol. Chem., November 7, 2003; 278(45): 44128 - 44138. [Abstract] [Full Text] [PDF]
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 J. J. Partridge, J. O. Lopreiato Jr., M. Latterich, and F. E. Indig DNA Damage Modulates Nucleolar Interaction of the Werner Protein with the AAA ATPase p97/VCP Mol. Biol. Cell, October 1, 2003; 14(10): 4221 - 4229. [Abstract] [Full Text] [PDF]
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K. Baynton, M. Otterlei, M. Bjoras, C. von Kobbe, V. A. Bohr, and E. Seeberg WRN Interacts Physically and Functionally with the Recombination Mediator Protein RAD52 J. Biol. Chem., September 19, 2003; 278(38): 36476 - 36486. [Abstract] [Full Text] [PDF]
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O. Imamura and J. L. Campbell The human Bloom syndrome gene suppresses the DNA replication and repair defects of yeast dna2 mutants PNAS, July 8, 2003; 100(14): 8193 - 8198. [Abstract] [Full Text] [PDF]
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 P. L. Opresko, W.-H. Cheng, C. von Kobbe, J. A. Harrigan, and V. A. Bohr Werner syndrome and the function of the Werner protein; what they can teach us about the molecular aging process. Carcinogenesis, May 1, 2003; 24(5): 791 - 802. [Abstract] [Full Text] [PDF]
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H. Oh, S. C. Wang, A. Prahash, M. Sano, C. S. Moravec, G. E. Taffet, L. H. Michael, K. A. Youker, M. L. Entman, and M. D. Schneider Telomere attrition and Chk2 activation in human heart failure PNAS, April 29, 2003; 100(9): 5378 - 5383. [Abstract] [Full Text] [PDF]
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