Changes in mobility account for camptothecin-induced subnuclear relocation of topoisomerase I.

The Journal of Biological Chemistry
Morten O ChristensenChristian Mielke

Abstract

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, wh...Continue Reading

References

Jan 1, 1989·Annual Review of Biochemistry·L F Liu
Feb 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·H ZhangL F Liu
Mar 24, 1999·Trends in Cell Biology·J White, E Stelzer
Jun 8, 1999·Molecular Biology of the Cell·M J HendzelD P Bazett-Jones
Apr 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y MaoL F Liu
Apr 15, 2000·Nature·R D Phair, T Misteli
Jul 13, 2000·The Journal of Cell Biology·L S Shopland, J B Lawrence
Dec 29, 2000·Nature·T MisteliD T Brown
Jun 8, 2001·Annual Review of Biochemistry·J J Champoux

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Citations

Apr 15, 2005·Chromosoma·John B Leppard, James J Champoux
Jan 25, 2003·Methods : a Companion to Methods in Enzymology·Gustavo CarreroMichael J Hendzel
Apr 6, 2004·Molecular Biology of the Cell·Lars SchmiedebergPeter Hemmerich
Dec 5, 2003·Nucleic Acids Research·Morten O ChristensenChristian Mielke
Oct 31, 2003·Molecular and Cellular Biology·Morten SunesenJean-Pierre Changeux
Feb 8, 2006·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Christiane St-AmantGuylain Boissonneault
Dec 15, 2010·Molecular Microbiology·Betty M BookerN Patrick Higgins
Sep 2, 2009·Nucleic Acids Research·Ilaria Dalla RosaMorten O Christensen
Oct 7, 2004·International Review of Cytology·Patrick J Dimario
Jul 25, 2013·ChemMedChem·Amanda J Pickard, Ulrich Bierbach
Jul 19, 2016·Journal of Cellular Biochemistry·Agnieszka GirstunKrzysztof Staron
Mar 27, 2004·The Journal of Biological Chemistry·Christian MielkeFritz Boege
Oct 21, 2004·The Journal of Biological Chemistry·Hans U BarthelmesDoris Marko
Feb 19, 2019·Journal of Cellular Biochemistry·Agnieszka GirstunKrzysztof Staron
May 14, 2009·Cancer Research·Nicolas HumbertDavid Bernard
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