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

被引:61
作者
Laman, H
Coverley, D
Krude, T
Laskey, R
Jones, N
机构
[1] Christie Hosp NHS Trust, Paterson Inst Canc Res, Manchester M20 4BX, Lancs, England
[2] Univ Cambridge, Dept Zool, Wellcome CRC Inst, Cambridge CB2 1QR, England
[3] Imperial Canc Res Fund, Gene Regulat Lab, London WC2A 3PX, England
关键词
D O I
10.1128/MCB.21.2.624-635.2001
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:624 / 635
页数:12
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