This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chang, D. Articles by Ljungman, M. Search for Related Content PubMed PubMed Citation Articles by Chang, D. Articles by Ljungman, M.

Dose-dependent Effects of DNA-damaging Agents on p53-mediated Cell Cycle Arrest¹

Department of Radiation Oncology, Division of Cancer Biology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan 48109-0582

We examined the dose-dependent effects of DNA-damaging agents on G₁ arrest in isogenic human cell lines differing in their p53 status. As expected, 5 or 20 Gy of ionizing radiation induced a p53-dependent G₁ arrest. In contrast, UV light or actinomycin D induced a modest G₁ arrest that was p53-dependent only at lower doses. At higher doses, cells were arrested in G₁ in a p53-independent manner coinciding with inhibition of RNA synthesis and abolished cyclin E expression. Interestingly, expression of cyclin E was enhanced after exposure to moderate doses of UV light and actinomycin D, and this enhancement was suppressed by wild-type p53. We propose that agents inducing transcription-blocking DNA lesions will at higher doses inhibit the progression of cells into S phase by a p53-independent mechanism involving the attenuation of E2F-mediated transcription of genes, such as cyclin E.

This article has been cited by other articles:

				A. B. Salmon, M. Ljungman, and R. A. Miller Cells From Long-Lived Mutant Mice Exhibit Enhanced Repair of Ultraviolet Lesions J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2008; 63(3): 219 - 231. [Abstract] [Full Text] [PDF]

				S. Ulisse, E. Baldini, M. Toller, J.-G. Delcros, A. Gueho, F. Curcio, E. De Antoni, L. Giacomelli, F. S Ambesi-Impiombato, S. Bocchini, et al. Transforming acidic coiled-coil 3 and Aurora-A interact in human thyrocytes and their expression is deregulated in thyroid cancer tissues Endocr. Relat. Cancer, September 1, 2007; 14(3): 827 - 837. [Abstract] [Full Text] [PDF]

				L. E. Giono and J. J. Manfredi Mdm2 Is Required for Inhibition of Cdk2 Activity by p21, Thereby Contributing to p53-Dependent Cell Cycle Arrest Mol. Cell. Biol., June 1, 2007; 27(11): 4166 - 4178. [Abstract] [Full Text] [PDF]

				D. A. Maiguel, L. Jones, D. Chakravarty, C. Yang, and F. Carrier Nucleophosmin Sets a Threshold for p53 Response to UV Radiation Mol. Cell. Biol., May 1, 2004; 24(9): 3703 - 3711. [Abstract] [Full Text] [PDF]

				L. C. Tu, T. Melendy, and T. A. Beerman DNA damage responses triggered by a highly cytotoxic monofunctional DNA alkylator, hedamycin, a pluramycin antitumor antibiotic Mol. Cancer Ther., May 1, 2004; 3(5): 577 - 586. [Abstract] [Full Text] [PDF]

				P.-r. Cao, M. M. McHugh, T. Melendy, and T. Beerman The DNA Minor Groove-alkylating Cyclopropylpyrroloindole Drugs Adozelesin and Bizelesin Induce Different DNA Damage Response Pathways in Human Colon Carcinoma HCT116 Cells Mol. Cancer Ther., July 1, 2003; 2(7): 651 - 659. [Abstract] [Full Text] [PDF]

				M. L. Smith and Y. R. Seo p53 regulation of DNA excision repair pathways Mutagenesis, March 1, 2002; 17(2): 149 - 156. [Abstract] [Full Text] [PDF]

				M. Loignon and E. A. Drobetsky The initiation of UV-induced G1 arrest in human cells is independent of the p53/p21/pRb pathway but can be attenuated through expression of the HPV E7 oncoprotein Carcinogenesis, January 1, 2002; 23(1): 35 - 45. [Abstract] [Full Text] [PDF]

				B. C. McKay, F. Chen, C. R. Perumalswami, F. Zhang, and M. Ljungman The Tumor Suppressor p53 Can Both Stimulate and Inhibit Ultraviolet Light-induced Apoptosis Mol. Biol. Cell, August 1, 2000; 11(8): 2543 - 2551. [Abstract] [Full Text]

				F. Chen, D. Chang, M. Goh, S. A. Klibanov, and M. Ljungman Role of p53 in Cell Cycle Regulation and Apoptosis following Exposure to Proteasome Inhibitors Cell Growth Differ., May 1, 2000; 11(5): 239 - 246. [Abstract] [Full Text]

				R. K. Geyer, H. Nagasawa, J. B. Little, and C. G. Maki Role and Regulation of p53 during an Ultraviolet Radiation-induced G1 Cell Cycle Arrest Cell Growth Differ., March 1, 2000; 11(3): 149 - 156. [Abstract] [Full Text]

				S. H. Khan, J. Moritsugu, and G. M. Wahl Differential requirement for p19ARF in the p53-dependent arrest induced by DNA damage, microtubule disruption, and ribonucleotide depletion PNAS, March 28, 2000; 97(7): 3266 - 3271. [Abstract] [Full Text] [PDF]

				M. van Oosten, H. Rebel, E. C. Friedberg, H. van Steeg, G. T. J. van der Horst, H. J. van Kranen, A. Westerman, A. A. van Zeeland, L. H. F. Mullenders, and F. R. de Gruijl Differential role of transcription-coupled repair in UVB-induced G2 arrest and apoptosis in mouse epidermis PNAS, October 10, 2000; 97(21): 11268 - 11273. [Abstract] [Full Text] [PDF]