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Science 6 June 1986:
Vol. 232. no. 4755, pp. 1264 - 1266
DOI: 10.1126/science.2422760
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Articles

Science, Vol 232, Issue 4755, 1264-1266
Copyright © 1986 by American Association for the Advancement of Science

articles

Caffeine-induced uncoupling of mitosis from the completion of DNA replication in mammalian cells

R Schlegel and AB Pardee

Caffeine was shown to induce mitotic events in mammalian cells before DNA replication (S phase) was completed. Synchronized BHK cells that were arrested in early S phase underwent premature chromosome condensation, nuclear envelope breakdown, morphological "rounding up," and mitosis-specific phosphoprotein synthesis when they were exposed to caffeine. These mitotic responses occurred only after the cells had entered S phase and only while DNA synthesis was inhibited by more than 70 percent. Inhibitors of protein synthesis blocked these caffeine-induced events, while inhibitors of RNA synthesis had little effect. These results suggest that caffeine induces the translation or stabilizes the protein product (or products) of mitosis-related RNA that accumulates in S-phase cells when DNA replication is suppressed. The ability to chemically manipulate the onset of mitosis should be useful for studying the regulation of this event in mammalian cells.


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Centromeric DNA cloned from functional kinetochore fragments in mitotic cells with unreplicated genomes.
I. Ouspenski and B. Brinkley (1993)
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Coordinating Cell Cycle Events.
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Differences in Mitotic Control among Mammalian Cells.
R.T. Schimke, A.L. Kung, D.F. Rush, and S.W. Sherwood (1991)
Cold Spring Harb Symp Quant Biol 56, 417-425
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Checkpoints: controls that ensure the order of cell cycle events.
L. Hartwell and T. Weinert (1989)
Science 246, 629-634
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Isolation and characterization of the active cDNA of the human cell cycle gene (RCC1) involved in the regulation of onset of chromosome condensation..
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The Radioresistance to Killing of A1-5 Cells Derives from Activation of the Chk1 Pathway.
B. Hu, X.-Y. Zhou, X. Wang, Z.-C. Zeng, G. Iliakis, and Y. Wang (2001)
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Aphidicolin Triggers a Block to Replication Origin Firing in Xenopus Egg Extracts.
K. Marheineke and O. Hyrien (2001)
J. Biol. Chem. 276, 17092-17100
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Inhibition of the G2 DNA Damage Checkpoint and of Protein Kinases Chk1 and Chk2 by the Marine Sponge Alkaloid Debromohymenialdisine.
D. Curman, B. Cinel, D. E. Williams, N. Rundle, W. D. Block, A. A. Goodarzi, J. R. Hutchins, P. R. Clarke, B.-B. Zhou, S. P. Lees-Miller, et al. (2001)
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