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A more recent version of this article appeared on May 1, 2006
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Submitted on November 14, 2005
Revised on February 22, 2006
Accepted on February 28, 2006
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139
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 rereplication act redundantly to inhibit pre-Replicative Complex (pre-RC) assembly outside of the G1 phase of the cell cycle. The yeast S. cerevisiae has been a useful model organism to study how eukaryotic cells prevent replication origins from reinitiating during a single cell cycle. Using a rereplication-sensitive strain and DNA microarrays, we map sites across the S. cerevisiae genome that are rereplicated as well as sites of pre-RC formation during rereplication. Only a fraction of the genome is rereplicated by a subset of origins, some of which are capable of multiple reinitiation events. Translocation experiments demonstrate that origin-proximal sequences are sufficient to pre-dispose an origin to rereplication. Origins that reinitiate are largely limited to those that can recruit Mcm2-7 under rereplicating 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 rereplication.
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