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Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication.

dc.contributor.authorLaman, Heike
dc.contributor.authorCoverley, Dawn
dc.contributor.authorKrude, Torsten
dc.contributor.authorLaskey, Ronald
dc.contributor.authorJones, Nic
dc.date.accessioned2009-11-06T16:52:44Z
dc.date.available2009-11-06T16:52:44Z
dc.date.issued2001-01
dc.identifier.citationViral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. 2001, 21 (2):624-35 Mol. Cell. Biol.en
dc.identifier.issn0270-7306
dc.identifier.pmid11134348
dc.identifier.doi10.1128/MCB.21.2.624-635.2001
dc.identifier.urihttp://hdl.handle.net/10541/85609
dc.description.abstractThe 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-G(1)-phase nuclei. Viral cyclin-cdk6 complexes share this capacity with cyclin A-cdk2, demonstrating that in addition to functioning as G(1)-phase cyclin-cdk complexes, they function as S-phase cyclin-cdk complexes.
dc.language.isoenen
dc.subjectCultured Tumour Cellsen
dc.subject.mesh3T3 Cells
dc.subject.meshAnimals
dc.subject.meshCDC2-CDC28 Kinases
dc.subject.meshCyclin D1
dc.subject.meshCyclin E
dc.subject.meshCyclin-Dependent Kinase 2
dc.subject.meshCyclin-Dependent Kinase 4
dc.subject.meshCyclin-Dependent Kinase 6
dc.subject.meshCyclin-Dependent Kinases
dc.subject.meshCyclins
dc.subject.meshDNA Replication
dc.subject.meshDNA-Binding Proteins
dc.subject.meshG1 Phase
dc.subject.meshHerpesviridae
dc.subject.meshHerpesvirus 8, Human
dc.subject.meshHumans
dc.subject.meshMice
dc.subject.meshMicroscopy, Fluorescence
dc.subject.meshOrigin Recognition Complex
dc.subject.meshPhosphorylation
dc.subject.meshProtein Binding
dc.subject.meshProtein-Serine-Threonine Kinases
dc.subject.meshProto-Oncogene Proteins
dc.subject.meshPurines
dc.subject.meshS Phase
dc.subject.meshTransfection
dc.subject.meshTumor Cells, Cultured
dc.subject.meshViral Proteins
dc.titleViral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication.en
dc.typeArticleen
dc.contributor.departmentGene Regulation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.en
dc.identifier.journalMolecular and Cellular Biologyen
html.description.abstractThe 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-G(1)-phase nuclei. Viral cyclin-cdk6 complexes share this capacity with cyclin A-cdk2, demonstrating that in addition to functioning as G(1)-phase cyclin-cdk complexes, they function as S-phase cyclin-cdk complexes.


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