Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication.
AffiliationGene Regulation Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, United Kingdom.
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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.
CitationViral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. 2001, 21 (2):624-35 Mol. Cell. Biol.
JournalMolecular and Cellular Biology