QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text 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 Borel, F. Articles by Margolis, R. L. Search for Related Content PubMed PubMed Citation Articles by Borel, F. Articles by Margolis, R. L. Social Bookmarking                         What's this?

Prolonged arrest of mammalian cells at the G1/S boundary results in permanent S phase stasis

Institut de Biologie Structurale J-P Ebel (CEA-CNRS), 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France

^* Author for correspondence (e-mail: margolis{at}ibs.fr )

Accepted 29 April 2002

Mammalian cells in culture normally enter a state of quiescence during G1 following suppression of cell cycle progression by senescence, contact inhibition or terminal differentiation signals. We find that mammalian fibroblasts enter cell cycle stasis at the onset of S phase upon release from prolonged arrest with the inhibitors of DNA replication, hydroxyurea or aphidicolin. During arrest typical S phase markers remain present, and G0/G1 inhibitory signals such as p21^WAF1 and p27 are absent. Cell cycle stasis occurs in T-antigen transformed cells, indicating that p53 and pRB inhibitory circuits are not involved. While no DNA replication is evident in arrested cells, nuclei isolated from these cells retain measurable competence for in vitro replication. MCM proteins are required to license replication origins, and are put in place in nuclei in G1 and excluded from chromatin by the end of replication to prevent rereplication of the genome. Strikingly, MCM proteins are strongly depleted from chromatin during prolonged S phase arrest, and their loss may underlie the observed cell cycle arrest. S phase stasis may thus be a `trap' in which cells otherwise competent for S phase have lost a key component required for replication and thus can neither go forward nor retreat to G1 status.

Key words: S phase stasis, S phase, Mammalian, MCM proteins, Hydroxyurea, Aphidicolin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				H. Hu, J. Zhang, H. J. Lee, S.-H. Kim, and J. Lu Penta-O-galloyl-beta-D-glucose induces S- and G1-cell cycle arrests in prostate cancer cells targeting DNA replication and cyclin D1 Carcinogenesis, May 1, 2009; 30(5): 818 - 823. [Abstract] [Full Text] [PDF]

				M. Iizuka, O. F. Sarmento, T. Sekiya, H. Scrable, C. D. Allis, and M. M. Smith Hbo1 Links p53-Dependent Stress Signaling to DNA Replication Licensing Mol. Cell. Biol., January 1, 2008; 28(1): 140 - 153. [Abstract] [Full Text] [PDF]

				A. Marusyk, L. J. Wheeler, C. K. Mathews, and J. DeGregori p53 Mediates Senescence-Like Arrest Induced by Chronic Replicational Stress Mol. Cell. Biol., August 1, 2007; 27(15): 5336 - 5351. [Abstract] [Full Text] [PDF]

				D. Wilsker and F. Bunz Loss of ataxia telangiectasia mutated- and Rad3-related function potentiates the effects of chemotherapeutic drugs on cancer cell survival Mol. Cancer Ther., April 1, 2007; 6(4): 1406 - 1413. [Abstract] [Full Text] [PDF]

				J. H. Yu and D. V. Schaffer High-throughput, library-based selection of a murine leukemia virus variant to infect nondividing cells. J. Virol., September 1, 2006; 80(18): 8981 - 8988. [Abstract] [Full Text] [PDF]

				H. Si and E. S. Robertson Kaposi's Sarcoma-Associated Herpesvirus-Encoded Latency-Associated Nuclear Antigen Induces Chromosomal Instability through Inhibition of p53 Function J. Virol., January 15, 2006; 80(2): 697 - 709. [Abstract] [Full Text] [PDF]

				N. Kothapalli, G. Sarath, and J. Zempleni Biotinylation of K12 in Histone H4 Decreases in Response to DNA Double-Strand Breaks in Human JAr Choriocarcinoma Cells J. Nutr., October 1, 2005; 135(10): 2337 - 2342. [Abstract] [Full Text] [PDF]

				A. Montagnoli, P. Tenca, F. Sola, D. Carpani, D. Brotherton, C. Albanese, and C. Santocanale Cdc7 Inhibition Reveals a p53-Dependent Replication Checkpoint That Is Defective in Cancer Cells Cancer Res., October 1, 2004; 64(19): 7110 - 7116. [Abstract] [Full Text] [PDF]

				S. P. Angus, C. N. Mayhew, D. A. Solomon, W. A. Braden, M. P. Markey, Y. Okuno, M. C. Cardoso, D. M. Gilbert, and E. S. Knudsen RB Reversibly Inhibits DNA Replication via Two Temporally Distinct Mechanisms Mol. Cell. Biol., June 15, 2004; 24(12): 5404 - 5420. [Abstract] [Full Text] [PDF]

				V. Gottifredi, K. McKinney, M. V. Poyurovsky, and C. Prives Decreased p21 Levels Are Required for Efficient Restart of DNA Synthesis after S Phase Block J. Biol. Chem., February 13, 2004; 279(7): 5802 - 5810. [Abstract] [Full Text] [PDF]

				A. Bhattacharya, J. M. Deng, Z. Zhang, R. Behringer, B. de Crombrugghe, and S. N. Maity The B Subunit of the CCAAT Box Binding Transcription Factor Complex (CBF/NF-Y) Is Essential for Early Mouse Development and Cell Proliferation Cancer Res., December 1, 2003; 63(23): 8167 - 8172. [Abstract] [Full Text] [PDF]

				O. D. Lohez, C. Reynaud, F. Borel, P. R. Andreassen, and R. L. Margolis Arrest of mammalian fibroblasts in G1 in response to actin inhibition is dependent on retinoblastoma pocket proteins but not on p53 J. Cell Biol., April 14, 2003; 161(1): 67 - 77. [Abstract] [Full Text] [PDF]