QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 16, Issue 1, 421-432, January 2005

This Article Full Text Full Text (PDF) All Versions of this Article: E04-09-0833v1 16/1/421    most recent 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 Green, B. M. Articles by Li, J. J. Search for Related Content PubMed PubMed Citation Articles by Green, B. M. Articles by Li, J. J.

Loss of Rereplication Control in Saccharomyces cerevisiae Results in Extensive DNA Damage

Brian M. Green ^*, and Joachim J. Li  

^* Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94143-2200; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143-2200

Submitted September 23, 2004; Revised October 26, 2004; Accepted October 28, 2004
Monitoring Editor: Orna Cohen-Fix

To maintain genome stability, the entire genome of a eukaryotic cell must be replicated once and only once per cell cycle. In many organisms, multiple overlapping mechanisms block rereplication, but the consequences of deregulating these mechanisms are poorly understood. Here, we show that disrupting these controls in the budding yeast Saccharomyces cerevisiae rapidly blocks cell proliferation. Rereplicating cells activate the classical DNA damage-induced checkpoint response, which depends on the BRCA1 C-terminus checkpoint protein Rad9. In contrast, Mrc1, a checkpoint protein required for recognition of replication stress, does not play a role in the response to rereplication. Strikingly, rereplicating cells accumulate subchromosomal DNA breakage products. These rapid and severe consequences suggest that even limited and sporadic rereplication could threaten the genome with significant damage. Hence, even subtle disruptions in the cell cycle regulation of DNA replication may predispose cells to the genomic instability associated with tumorigenesis.

Corresponding author. E-mail address: jli{at}itsa.ucsf.edu.

This article has been cited by other articles:

				E. Liu, A. Y.-L. Lee, T. Chiba, E. Olson, P. Sun, and X. Wu The ATR-mediated S phase checkpoint prevents rereplication in mammalian cells when licensing control is disrupted J. Cell Biol., November 19, 2007; 179(4): 643 - 657. [Abstract] [Full Text] [PDF]

				A. Y.-L. Lee, E. Liu, and X. Wu The Mre11/Rad50/Nbs1 Complex Plays an Important Role in the Prevention of DNA Rereplication in Mammalian Cells J. Biol. Chem., November 2, 2007; 282(44): 32243 - 32255. [Abstract] [Full Text] [PDF]

				S. Honey and B. Futcher Roles of the CDK Phosphorylation Sites of Yeast Cdc6 in Chromatin Binding and Rereplication Mol. Biol. Cell, April 1, 2007; 18(4): 1324 - 1336. [Abstract] [Full Text] [PDF]

				E. E. Arias and J. C. Walter Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells Genes & Dev., March 1, 2007; 21(5): 497 - 518. [Abstract] [Full Text] [PDF]

				A. E. Ikui, V. Archambault, B. J. Drapkin, V. Campbell, and F. R. Cross Cyclin and Cyclin-Dependent Kinase Substrate Requirements for Preventing Rereplication Reveal the Need for Concomitant Activation and Inhibition Genetics, March 1, 2007; 175(3): 1011 - 1022. [Abstract] [Full Text] [PDF]

				S. Laha, S. P. Das, S. Hajra, S. Sau, and P. Sinha The budding yeast protein Chl1p is required to preserve genome integrity upon DNA damage in S-phase Nucleic Acids Res., November 6, 2006; 34(20): 5880 - 5891. [Abstract] [Full Text] [PDF]

				C. A. Lovejoy, K. Lock, A. Yenamandra, and D. Cortez DDB1 Maintains Genome Integrity through Regulation of Cdt1 Mol. Cell. Biol., November 1, 2006; 26(21): 7977 - 7990. [Abstract] [Full Text] [PDF]

				Y. Tatsumi, N. Sugimoto, T. Yugawa, M. Narisawa-Saito, T. Kiyono, and M. Fujita Deregulation of Cdt1 induces chromosomal damage without rereplication and leads to chromosomal instability J. Cell Sci., August 1, 2006; 119(15): 3128 - 3140. [Abstract] [Full Text] [PDF]

				B. M. Green, R. J. Morreale, B. Ozaydin, J. L. DeRisi, and J. J. Li Genome-wide Mapping of DNA Synthesis in Saccharomyces cerevisiae Reveals That Mechanisms Preventing Reinitiation of DNA Replication Are Not Redundant Mol. Biol. Cell, May 1, 2006; 17(5): 2401 - 2414. [Abstract] [Full Text] [PDF]

				R. E. Tanny, D. M. MacAlpine, H. G. Blitzblau, and S. P. Bell Genome-wide Analysis of Re-replication Reveals Inhibitory Controls That Target Multiple Stages of Replication Initiation Mol. Biol. Cell, May 1, 2006; 17(5): 2415 - 2423. [Abstract] [Full Text] [PDF]

				D. Remus, M. Blanchette, D. C. Rio, and M. R. Botchan CDK Phosphorylation Inhibits the DNA-binding and ATP-hydrolysis Activities of the Drosophila Origin Recognition Complex J. Biol. Chem., December 2, 2005; 280(48): 39740 - 39751. [Abstract] [Full Text] [PDF]

				M. E. Liku, V. Q. Nguyen, A. W. Rosales, K. Irie, and J. J. Li CDK Phosphorylation of a Novel NLS-NES Module Distributed between Two Subunits of the Mcm2-7 Complex Prevents Chromosomal Rereplication Mol. Biol. Cell, October 1, 2005; 16(10): 5026 - 5039. [Abstract] [Full Text] [PDF]

				V. Archambault, A. E. Ikui, B. J. Drapkin, and F. R. Cross Disruption of Mechanisms That Prevent Rereplication Triggers a DNA Damage Response Mol. Cell. Biol., August 1, 2005; 25(15): 6707 - 6721. [Abstract] [Full Text] [PDF]