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

2.50
Hdl Handle:
http://hdl.handle.net/10541/85609
Title:
Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication.
Authors:
Laman, Heike; Coverley, Dawn; Krude, Torsten; Laskey, Ronald; Jones, Nic
Abstract:
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-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.
Affiliation:
Gene Regulation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
Citation:
Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. 2001, 21 (2):624-35 Mol. Cell. Biol.
Journal:
Molecular and Cellular Biology
Issue Date:
Jan-2001
URI:
http://hdl.handle.net/10541/85609
DOI:
10.1128/MCB.21.2.624-635.2001
PubMed ID:
11134348
Type:
Article
Language:
en
ISSN:
0270-7306
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorLaman, Heikeen
dc.contributor.authorCoverley, Dawnen
dc.contributor.authorKrude, Torstenen
dc.contributor.authorLaskey, Ronalden
dc.contributor.authorJones, Nicen
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.en
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

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