Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication.
Laman, Heike Coverley, Dawn Krude, Torsten Laskey, Ronald Jones, Nic
Laman, Heike
Coverley, Dawn
Krude, Torsten
Laskey, Ronald
Jones, Nic
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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.
Description
Date
2001-01
Publisher
Collections
Keywords
Cultured Tumour Cells
Type
Article
Citation
Viral cyclin-cyclin-dependent kinase 6 complexes initiate nuclear DNA replication. 2001, 21 (2):624-35 Mol. Cell. Biol.