Role for cyclin A-dependent kinase in DNA replication in human S phase cell extracts.

The Journal of Biological Chemistry
A FotedarR Fotedar

Abstract

Cell cycle progression is regulated by cyclin-dependent kinases. Using in vitro replication of SV40 origin containing DNA as a model system, we have performed a detailed analysis of the dependence on cyclin-associated kinases of mammalian DNA replication. Complete immunodepletion of cyclin A from human S phase cell extracts decreases replication, and replication activity of cyclin A-depleted S phase extracts can subsequently be restored by the addition of purified CDK2-cyclin A kinase. Addition of cyclin A alone reconstitutes both kinase activity and DNA replication, whereas addition of cyclin E or cyclin B reconstitutes neither. We therefore conclude that reconstitution of DNA replication specifically correlates with an increase in kinase activity. By comparison, depletion of cyclin E from S phase cell extracts does not have any significant inhibitory effect on DNA replication. Moreover, specific p21(Waf1) mutants that bind to CDK2-cyclin and inhibit both cyclin A and cyclin E kinase activities, but do not bind to proliferating cell nuclear antigen, inhibit DNA replication to the same extent as cyclin A depletion. Together, these results show that the kinase activity associated with cyclin A, but not with cyclin E, is primaril...Continue Reading

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Citations

Feb 13, 2008·Molecular Biotechnology·Anna Philpott, P Renee Yew
Feb 13, 2009·Molecular Biology of the Cell·Jinho LeeRati Fotedar
Jun 20, 2001·Journal of Virology·S SchüchnerE Wintersberger
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Aug 16, 2021·The Journal of Biological Chemistry·Nathan A Snyder, Gustavo M Silva

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