Identification of a Preinitiation Step in DNA Replication That Is Independent of Origin Recognition Complex and cdc6, but Dependent on cdk2

doi:10.1083/jcb.140.2.271

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© The Rockefeller University Press, 0021-9525/1998//271 $5.00
The Journal of Cell Biology, Volume 140, Number 2, , 1998 271-281

Article

Identification of a Preinitiation Step in DNA Replication That Is Independent of Origin Recognition Complex and cdc6, but Dependent on cdk2

Xuequn Helen Hua and John Newport

Biology Department, University of California, San Diego, CA 92093-0347

Before initiation of DNA replication, origin recognition complex(ORC) proteins, cdc6, and minichromosome maintenance (MCM) proteinsbind to chromatin sequentially and form preinitiation complexes.Using Xenopus laevis egg extracts, we find that after the formationof these complexes and before initiation of DNA replication,cdc6 is rapidly removed from chromatin, possibly degraded bya cdk2-activated, ubiquitin-dependent proteolytic pathway.If this displacement is inhibited, DNA replication fails toinitiate. We also find that after assembly of MCM proteinsinto preinitiation complexes, removal of the ORC from DNAdoes not block the subsequent initiation of replication. Importantly,under conditions in which both ORC and cdc6 protein are absentfrom preinitiation complexes, DNA replication is still dependenton cdk2 activity. Therefore, the final steps in the processleading to initiation of DNA replication during S phase ofthe cell cycle are independent of ORC and cdc6 proteins, butdependent on cdk2 activity.

Abbreviations used in this paper: ELB, egg lysis buffer; MCM, minichromosome maintenance; ORC, origin recognition complex.

Address all correspondence to J. Newport, Biology Department,0347, University of California, San Diego, 9500 Gilman Drive,La Jolla, CA 92093-0347. Tel.: (619) 534-3423. Fax: (619) 534-0555.E-mail: jnewport{at}ucsd.edu

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