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Vol. 17, Issue 5, 2415-2423, May 2006
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Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
Submitted November 14, 2005;
Revised February 22, 2006;
Accepted February 28, 2006
Monitoring Editor: Orna Cohen-Fix
DNA replication must be tightly controlled during each cell cycle to prevent unscheduled replication and ensure proper genome maintenance. The currently known controls that prevent re-replication act redundantly to inhibit pre-replicative complex (pre-RC) assembly outside of the G1-phase of the cell cycle. The yeast Saccharomyces cerevisiae has been a useful model organism to study how eukaryotic cells prevent replication origins from reinitiating during a single cell cycle. Using a re-replication-sensitive strain and DNA microarrays, we map sites across the S. cerevisiae genome that are re-replicated as well as sites of pre-RC formation during re-replication. Only a fraction of the genome is re-replicated by a subset of origins, some of which are capable of multiple reinitiation events. Translocation experiments demonstrate that origin-proximal sequences are sufficient to predispose an origin to re-replication. Origins that reinitiate are largely limited to those that can recruit Mcm2-7 under re-replicating conditions; however, the formation of a pre-RC is not sufficient for reinitiation. Our findings allow us to categorize origins with respect to their propensity to reinitiate and demonstrate that pre-RC formation is not the only target for the mechanisms that prevent genomic re-replication.
Abbreviations used: ORC, origin recognition complex; pre-RC, pre-replicative complex; CDK, cyclin-dependent kinase; ACS, ARS consensus sequence; HU, hydroxyurea.
The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).
Address correspondence to: Stephen P. Bell (spbell{at}mit.edu).
This article has been cited by other articles:
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  C. Speck and B. Stillman Cdc6 ATPase Activity Regulates ORC{middle dot}Cdc6 Stability and the Selection of Specific DNA Sequences as Origins of DNA Replication J. Biol. Chem., April 20, 2007; 282(16): 11705 - 11714. [Abstract] [Full Text] [PDF]
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 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]
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K. A. Braun and L. L. Breeden Nascent Transcription of MCM2-7 Is Important for Nuclear Localization of the Minichromosome Maintenance Complex in G1 Mol. Biol. Cell, April 1, 2007; 18(4): 1447 - 1456. [Abstract] [Full Text] [PDF]
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 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]
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 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]
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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]
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