This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend 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 Huang, Y. Articles by Yuan, Z.-M. Search for Related Content PubMed PubMed Citation Articles by Huang, Y. Articles by Yuan, Z.-M.

Role for E2F in DNA Damage-induced Entry of Cells into S Phase¹

Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

Mammalian cells respond to ionizing radiation (IR) with transient cell cycle arrest and induction of apoptosis. Here we show that IR increases the expression of the E2F-1 transcription factor and the entry of cells into S phase. E2F-1 transactivation function is inhibited by cyclin A-kinase to ensure orderly progression through S phase. However, in contrast to proliferating cells, IR treatment results in down-regulation of cyclin A-kinase. Expression of a dominant negative form of the E2F heterodimeric partner DP-1 confirmed the involvement of E2F in IR-induced S-phase entry. These findings also support opposing signals involving the induction of E2F and the down-regulation of cyclin A-kinase in the IR response.

¹ Supported by USPHS Grant CA55241 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed. Phone: (617) 632-3142; Fax: (617) 632-2934.

Received 6/11/97. Accepted 7/14/97.

This article has been cited by other articles:

				E.L. Crawford, T. Blomquist, D.N. Mullins, Y. Yoon, D.R. Hernandez, M. Al-Bagdhadi, J. Ruiz, J. Hammersley, and J.C. Willey CEBPG regulates ERCC5/XPG expression in human bronchial epithelial cells and this regulation is modified by E2F1/YY1 interactions Carcinogenesis, December 1, 2007; 28(12): 2552 - 2559. [Abstract] [Full Text] [PDF]

				H. A. Rogoff, M. T. Pickering, F. M. Frame, M. E. Debatis, Y. Sanchez, S. Jones, and T. F. Kowalik Apoptosis Associated with Deregulated E2F Activity Is Dependent on E2F1 and Atm/Nbs1/Chk2 Mol. Cell. Biol., April 1, 2004; 24(7): 2968 - 2977. [Abstract] [Full Text] [PDF]

				O. Petrenko, G. Fingerle-Rowson, T. Peng, R. A. Mitchell, and C. N. Metz Macrophage Migration Inhibitory Factor Deficiency Is Associated with Altered Cell Growth and Reduced Susceptibility to Ras-mediated Transformation J. Biol. Chem., March 21, 2003; 278(13): 11078 - 11085. [Abstract] [Full Text] [PDF]

				S. Polager and D. Ginsberg E2F Mediates Sustained G2 Arrest and Down-regulation of Stathmin and AIM-1 Expression in Response to Genotoxic Stress J. Biol. Chem., January 10, 2003; 278(3): 1443 - 1449. [Abstract] [Full Text] [PDF]

				Z. Han, W. Wei, S. Dunaway, J. W. Darnowski, P. Calabresi, J. Sedivy, E. A. Hendrickson, K. V. Balan, P. Pantazis, and J. H. Wyche Role of p21 in Apoptosis and Senescence of Human Colon Cancer Cells Treated with Camptothecin J. Biol. Chem., May 3, 2002; 277(19): 17154 - 17160. [Abstract] [Full Text] [PDF]

				W.-C. Lin, F.-T. Lin, and J. R. Nevins Selective induction of E2F1 in response to DNA damage, mediated by ATM-dependent phosphorylation Genes & Dev., July 15, 2001; 15(14): 1833 - 1844. [Abstract] [Full Text] [PDF]

				Y. Zhang, A. K. Rishi, M. I. Dawson, R. Tschang, L. Farhana, M. Boyanapalli, U. Reichert, B. Shroot, E. C. Van Buren, and J. A. Fontana S-phase Arrest and Apoptosis Induced in Normal Mammary Epithelial Cells by a Novel Retinoid Cancer Res., April 1, 2000; 60(7): 2025 - 2032. [Abstract] [Full Text]

				C. Blattner, A. Sparks, and D. Lane Transcription Factor E2F-1 Is Upregulated in Response to DNA Damage in a Manner Analogous to That of p53 Mol. Cell. Biol., May 1, 1999; 19(5): 3704 - 3713. [Abstract] [Full Text] [PDF]

				D. Chang, F. Chen, F. Zhang, B. C. McKay, and M. Ljungman Dose-dependent Effects of DNA-damaging Agents on p53-mediated Cell Cycle Arrest Cell Growth Differ., March 1, 1999; 10(3): 155 - 162. [Abstract] [Full Text]