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15 Regulating Initiation Events in Yeasts

Etienne Schwob, Karim Labib


With very few exceptions, eukaryotic cells synthesize one complete copy of their chromosomes during each cell cycle, so that no stretch of DNA is replicated twice or left unreplicated by the time of mitosis. A single round of chromosome replication occurs during S phase, and this is achieved principally by ensuring that initiation at each origin of DNA replication can occur just once. An origin at which initiation has already taken place must be distinguishable from an origin that has yet to fire, as some origins are activated early during S phase and others later, and yet initiation at late origins is not associated with reinitiation at early origins. The regulation of initiation thus has two key features: The timing of initiation events at early and late origins must be controlled in order to determine the period of the cell cycle during which DNA synthesis occurs, and, most importantly, a mechanism must exist which ensures that initiation at each origin makes the origin inactive until the next round of cell division. The first of these features is discussed in Chapters 3 and 10; here we discuss how single-celled model organisms (budding yeast and fission yeast) have helped us to understand how eukaryotic cells ensure that initiation occurs just once at each origin of DNA replication.

We now know that Cyclin-Dependent Kinase (CDK) activity plays a key role in limiting chromosome replication to one round per cell cycle. The first evidence to this...

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