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Molecular and Cellular Biology, January 2001, p. 624-635, Vol. 21, No. 2
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.
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
*
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.
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