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Molecular and Cellular Biology, January 2001, p. 624-635, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.624-635.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Viral Cyclin-Cyclin-Dependent Kinase 6 Complexes Initiate Nuclear DNA Replication

Heike Laman,1 Dawn Coverley,2 Torsten Krude,2 Ronald Laskey,2 and Nic Jones1,3,*

Gene Regulation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX,1 Wellcome/CRC Institute, Department of Zoology, University of Cambridge, Cambridge CB2 1QR,2 and Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester M20 4BX,3 United Kingdom

Received 7 June 2000/Returned for modification 17 July 2000/Accepted 10 October 2000

The cyclins encoded by Kaposi sarcoma-associated herpesvirus and herpesvirus saimiri are homologs of human D-type cyclins. However, when complexed to cdk6, they have several activities that distinguish them from D-type cyclin-cdk6 complexes, including resistance to cyclin-dependent kinase inhibitors and an enhanced substrate range. We find that viral cyclins interact with and phosphorylate proteins involved in replication initiation. Using mammalian in vitro replication systems, we show that viral cyclin-cdk6 complexes can directly trigger the initiation of DNA synthesis in isolated late-G1-phase nuclei. Viral cyclin-cdk6 complexes share this capacity with cyclin A-cdk2, demonstrating that in addition to functioning as G1-phase cyclin-cdk complexes, they function as S-phase cyclin-cdk complexes.

* Corresponding author. Mailing address: Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Wilmslow Rd., Manchester M20 4BX, United Kingdom. Phone: 44-161-446-3101. Fax: 44-161-446-3038. E-mail: NJones{at}PICR.man.ac.uk.

Molecular and Cellular Biology, January 2001, p. 624-635, Vol. 21, No. 2
0270-7306/01/$04.00+0   DOI: 10.1128/MCB.21.2.624-635.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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