| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 18, 15661-15665, May 3, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the DNA topoisomerase I is a nucleolar protein, which
relocates to the nucleoplasm in response to drugs stabilizing
topoisomerase I·DNA intermediates (e.g. camptothecin).
Here we demonstrate that this phenomenon is solely caused by the
drug's impact on the interplay between mobility and localization of
topoisomerase I in a living cell nucleus. We show by photobleaching of
cells expressing biofluorescent topoisomerase I-chimera that the enzyme
moves continuously between nucleoli and nucleoplasm. Complex kinetics
of fluorescence recovery after photobleaching indicates that two enzyme
fractions with different mobility coexist in nucleoli and nucleoplasm.
However, the whole complement of topoisomerase I is in continuous
flux between these compartments and nucleolar accumulation can
plausibly explained by the enzyme's 2-fold lesser overall mobility in
nucleoli versus nucleoplasm. Upon addition of camptothecin,
topoisomerase I relocates within 30 s from the nucleoli to radial
nucleoplasmic structures. At these sites, the enzyme becomes retarded
in a dose-dependent manner. Inside nucleoli the mobility of
topoisomerase I is much less affected by camptothecin. Thus, the
enzyme's distribution equilibrium is shifted toward the nucleoplasm,
which causes nucleolar delocalization. In general, topoisomerase I is
an entirely mobile nuclear component, unlikely to require specific
signaling for movements between nuclear compartments.
Changes in Mobility Account for Camptothecin-induced Subnuclear
Relocation of Topoisomerase I*,
,,,, and¶
Department of Clinical Chemistry,
Medizinische Poliklinik, University of Würzburg, Klinikstrasse
6-8, D-97070 Würzburg, Germany and the § Department of
Molecular and Structural Biology, University of Aarhus, DK-8200
Aarhus-C, Denmark
*
This work was supported by the Deutsche
Forschungsgemeinschaft (Bo 910/3-1, Bo 910/4-1, GRK 639, and HA
1434/13-1) and the Danish Cancer Society (97-100-32).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
The on-line version of this article (available at
http://www.jbc.org) contains a QuickTime movie.
¶
To whom correspondence should be addressed. Tel.:
(49-931)201-70080; Fax: 49(931)201-70980; E-mail:
christian.mielke@mail. uni-wuerzburg.de.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  H. U. Barthelmes, M. Habermeyer, M. O. Christensen, C. Mielke, H. Interthal, J. J. Pouliot, F. Boege, and D. Marko TDP1 Overexpression in Human Cells Counteracts DNA Damage Mediated by Topoisomerases I and II J. Biol. Chem., December 31, 2004; 279(53): 55618 - 55625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. C. Yung, S. Sato, and M. S. Satoh Poly(ADP-ribosyl)ation as a DNA Damage-induced Post-translational Modification Regulating Poly(ADP-ribose) Polymerase-1-Topoisomerase I Interaction J. Biol. Chem., September 17, 2004; 279(38): 39686 - 39696. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Schmiedeberg, K. Weisshart, S. Diekmann, G. Meyer zu Hoerste, and P. Hemmerich High- and Low-mobility Populations of HP1 in Heterochromatin of Mammalian Cells Mol. Biol. Cell, June 1, 2004; 15(6): 2819 - 2833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Christensen, R. M. Krokowski, H. U. Barthelmes, R. Hock, F. Boege, and C. Mielke Distinct Effects of Topoisomerase I and RNA Polymerase I Inhibitors Suggest a Dual Mechanism of Nucleolar/Nucleoplasmic Partitioning of Topoisomerase I J. Biol. Chem., May 21, 2004; 279(21): 21873 - 21882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mielke, M. O. Christensen, H. U. Barthelmes, and F. Boege Enhanced Processing of UVA-irradiated DNA by Human Topoisomerase II in Living Cells J. Biol. Chem., May 14, 2004; 279(20): 20559 - 20562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. O. Christensen, H. U. Barthelmes, F. Boege, and C. Mielke Residues 190-210 of human topoisomerase I are required for enzyme activity in vivo but not in vitro Nucleic Acids Res., December 15, 2003; 31(24): 7255 - 7263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Sunesen, M. Huchet-Dymanus, M. O. Christensen, and J.-P. Changeux Phosphorylation-Elicited Quaternary Changes of GA Binding Protein in Transcriptional Activation Mol. Cell. Biol., November 15, 2003; 23(22): 8008 - 8018. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Dougherty, J. Wu, and R. A. Nichols {beta}-Amyloid Regulation of Presynaptic Nicotinic Receptors in Rat Hippocampus and Neocortex J. Neurosci., July 30, 2003; 23(17): 6740 - 6747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Rallabhandi, K. Hashimoto, Y.-Y. Mo, W. T. Beck, P. K. Moitra, and P. D'Arpa Sumoylation of Topoisomerase I Is Involved in Its Partitioning between Nucleoli and Nucleoplasm and Its Clearing from Nucleoli in Response to Camptothecin J. Biol. Chem., October 11, 2002; 277(42): 40020 - 40026. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Christensen, H. U. Barthelmes, F. Boege, and C. Mielke The N-terminal Domain Anchors Human Topoisomerase I at Fibrillar Centers of Nucleoli and Nucleolar Organizer Regions of Mitotic Chromosomes J. Biol. Chem., September 20, 2002; 277(39): 35932 - 35938. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
