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Originally published In Press as doi:10.1074/jbc.M103414200 on August 1, 2001

J. Biol. Chem., Vol. 276, Issue 40, 37166-37177, October 5, 2001
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The G2 DNA Damage Checkpoint Delays Expression of Genes Encoding Mitotic Regulators*

David F. CrawfordDagger § and Helen Piwnica-WormsDagger ||**

From the Dagger  Department of Cell Biology and Physiology, § Department of Pediatrics,  Department of Internal Medicine, and || Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Missouri 63110

Transcriptional control of gene expression contributes to the regulation of diverse cellular processes including cell cycle progression and the cellular response to DNA damage. Global gene expression profiling was performed using p53-deficient human cells to identify genes with G2/M-specific and DNA damage-responsive expression. Numerous cell cycle-regulated genes were identified, but surprisingly the analysis failed to identify genes activated by ionizing radiation. Instead, significant delays in expression of G2/M-specific genes, including known mitotic regulators, were observed following DNA damage. Thus, in the absence of p53, gene induction does not contribute to the G2 arrest following DNA damage. Rather, the DNA damage checkpoint elicits a G2 cell cycle arrest, in part, by delaying accumulation of proteins required in mitosis.

* This work was supported in part by a National Institutes of Health K08 award (to D. F. C).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.

** An Investigator of the Howard Hughes Medical Institute. To whom correspondence should be addressed: Dept. of Cell Biology and Physiology, Washington University School of Medicine, Box 8228, 660 S. Euclid Ave., St. Louis, MO 63110. E-mail: hpiwnica@cellbio.wustl.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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