This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Archambault, V.
Right arrow Articles by Cross, F. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Archambault, V.
Right arrow Articles by Cross, F. R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2005, p. 6707-6721, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6707-6721.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Disruption of Mechanisms That Prevent Rereplication Triggers a DNA Damage Response{dagger}

Vincent Archambault,{ddagger} Amy E. Ikui,{ddagger} Benjamin J. Drapkin, and Frederick R. Cross*

The Rockefeller University, New York, New York 10021

Received 21 September 2004/ Returned for modification 29 November 2004/ Accepted 4 May 2005

Eukaryotes replicate DNA once and only once per cell cycle due to multiple, partially overlapping mechanisms efficiently preventing reinitiation. The consequences of reinitiation are unknown. Here we show that the induction of rereplication by mutations in components of the prereplicative complex (origin recognition complex [ORC], Cdc6, and minichromosome maintenance proteins) causes a cell cycle arrest with activated Rad53, a large-budded morphology, and an undivided nucleus. Combining a mutation disrupting the Clb5-Orc6 interaction (ORC6-rxl) and a mutation stabilizing Cdc6 (CDC6{Delta}NT) causes a cell cycle delay with a similar phenotype, although this background is only partially compromised for rereplication control and does not exhibit overreplication detectable by fluorescence-activated cell sorting. We conducted a systematic screen that identified genetic requirements for the viability of these cells. ORC6-rxl CDC6{Delta}NT cells depend heavily on genes required for the DNA damage response and for double-strand-break repair by homologous recombination. Our results implicate an Mre11-Mec1-dependent pathway in limiting the extent of rereplication.

* Corresponding author. Mailing address: The Rockefeller University, 1230 York Ave., Box 237, New York, NY 10021. Phone: (212) 327-7685. Fax: (212) 327-7193. E-mail: fcross{at}rockefeller.edu.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} These authors contributed equally to this work.

Molecular and Cellular Biology, August 2005, p. 6707-6721, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6707-6721.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ikui, A. E., Cross, F. R. (2009). Specific Genetic Interactions Between Spindle Assembly Checkpoint Proteins and B-Type Cyclins in Saccharomyces cerevisiae. Genetics 183: 51-61 [Abstract] [Full Text]  
  • Makise, M., Takehara, M., Kuniyasu, A., Matsui, N., Nakayama, H., Mizushima, T. (2009). Linkage between Phosphorylation of the Origin Recognition Complex and Its ATP Binding Activity in Saccharomyces cerevisiae. J. Biol. Chem. 284: 3396-3407 [Abstract] [Full Text]  
  • Tsuyama, T., Watanabe, S., Aoki, A., Cho, Y., Seki, M., Enomoto, T., Tada, S. (2009). Repression of Nascent Strand Elongation by Deregulated Cdt1 during DNA Replication in Xenopus Egg Extracts. Mol. Biol. Cell 20: 937-947 [Abstract] [Full Text]  
  • Dorn, E. S., Chastain, P. D. II, Hall, J. R., Cook, J. G. (2009). Analysis of re-replication from deregulated origin licensing by DNA fiber spreading. Nucleic Acids Res 37: 60-69 [Abstract] [Full Text]  
  • Mehrotra, S., Maqbool, S. B., Kolpakas, A., Murnen, K., Calvi, B. R. (2008). Endocycling cells do not apoptose in response to DNA rereplication genotoxic stress. Genes Dev. 22: 3158-3171 [Abstract] [Full Text]  
  • Hall, J. R., Lee, H. O., Bunker, B. D., Dorn, E. S., Rogers, G. C., Duronio, R. J., Cook, J. G. (2008). Cdt1 and Cdc6 Are Destabilized by Rereplication-induced DNA Damage. J. Biol. Chem. 283: 25356-25363 [Abstract] [Full Text]  
  • Liu, E., Lee, A. Y.-L., Chiba, T., Olson, E., Sun, P., Wu, X. (2007). The ATR-mediated S phase checkpoint prevents rereplication in mammalian cells when licensing control is disrupted. JCB 179: 643-657 [Abstract] [Full Text]  
  • Lee, A. Y.-L., Liu, E., Wu, X. (2007). The Mre11/Rad50/Nbs1 Complex Plays an Important Role in the Prevention of DNA Rereplication in Mammalian Cells. J. Biol. Chem. 282: 32243-32255 [Abstract] [Full Text]  
  • Hall, J. R., Kow, E., Nevis, K. R., Lu, C. K., Luce, K. S., Zhong, Q., Cook, J. G. (2007). Cdc6 Stability Is Regulated by the Huwe1 Ubiquitin Ligase after DNA Damage. Mol. Biol. Cell 18: 3340-3350 [Abstract] [Full Text]  
  • Maxwell, P. H., Curcio, M. J. (2007). Host Factors That Control Long Terminal Repeat Retrotransposons in Saccharomyces cerevisiae: Implications for Regulation of Mammalian Retroviruses. Eukaryot Cell 6: 1069-1080 [Full Text]  
  • Honey, S., Futcher, B. (2007). Roles of the CDK Phosphorylation Sites of Yeast Cdc6 in Chromatin Binding and Rereplication. Mol. Biol. Cell 18: 1324-1336 [Abstract] [Full Text]  
  • Arias, E. E., Walter, J. C. (2007). Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev. 21: 497-518 [Abstract] [Full Text]  
  • Ikui, A. E., Archambault, V., Drapkin, B. J., Campbell, V., Cross, F. R. (2007). Cyclin and Cyclin-Dependent Kinase Substrate Requirements for Preventing Rereplication Reveal the Need for Concomitant Activation and Inhibition. Genetics 175: 1011-1022 [Abstract] [Full Text]  
  • Green, B. M., Morreale, R. J., Ozaydin, B., DeRisi, J. L., Li, J. J. (2006). Genome-wide Mapping of DNA Synthesis in Saccharomyces cerevisiae Reveals That Mechanisms Preventing Reinitiation of DNA Replication Are Not Redundant. Mol. Biol. Cell 17: 2401-2414 [Abstract] [Full Text]  
  • Tanny, R. E., MacAlpine, D. M., Blitzblau, H. G., Bell, S. P. (2006). Genome-wide Analysis of Re-replication Reveals Inhibitory Controls That Target Multiple Stages of Replication Initiation. Mol. Biol. Cell 17: 2415-2423 [Abstract] [Full Text]  
  • Liku, M. E., Nguyen, V. Q., Rosales, A. W., Irie, K., Li, J. J. (2005). CDK Phosphorylation of a Novel NLS-NES Module Distributed between Two Subunits of the Mcm2-7 Complex Prevents Chromosomal Rereplication. Mol. Biol. Cell 16: 5026-5039 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»