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Formation of a Preinitiation Complex by S-phase Cyclin CDK-Dependent Loading of Cdc45p onto Chromatin

Science  24 Apr 1998:
Vol. 280, Issue 5363, pp. 593-596
DOI: 10.1126/science.280.5363.593

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Abstract

Cdc45p, a protein essential for initiation of DNA replication, associates with chromatin after “start” in late G1 and during the S phase of the cell cycle. Binding of Cdc45p to chromatin depends on Clb-Cdc28 kinase activity as well as functional Cdc6p and Mcm2p, which suggests that Cdc45p associates with the prereplication complex after activation of S-phase cyclin-dependent kinases (CDKs). As indicated by the timing and the CDK dependence, binding of Cdc45p to chromatin is crucial for commitment to initiation of DNA replication. During S phase, Cdc45p physically interacts with minichromosome maintenance (MCM) proteins on chromatin; however, dissociation of Cdc45p from chromatin is slower than that of MCMs, which indicates that the proteins are released by different mechanisms.

  • * Is also a student in the Graduate Program in Molecular Genetics and Microbiology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.

  • To whom correspondence should be addressed. E-mail: stillman{at}cshl.org

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