Distinct roles for cyclins E and A during DNA replication complex assembly and activation View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2002-07

AUTHORS

Dawn Coverley, Heike Laman, Ronald A Laskey

ABSTRACT

Initiation of DNA replication is regulated by cyclin-dependent protein kinase 2 (Cdk2) in association with two different regulatory subunits, cyclin A and cyclin E (reviewed in ref. 1). But why two different cyclins are required and why their order of activation is tightly regulated are unknown. Using a cell-free system for initiation of DNA replication that is based on G1 nuclei, G1 cytosol and recombinant proteins, we find that cyclins E and A have specialized roles during the transition from G0 to S phase. Cyclin E stimulates replication complex assembly by cooperating with Cdc6, to make G1 nuclei competent to replicate in vitro. Cyclin A has two separable functions: it activates DNA synthesis by replication complexes that are already assembled, and it inhibits the assembly of new complexes. Thus, cyclin E opens a 'window of opportunity' for replication complex assembly that is closed by cyclin A. The dual functions of cyclin A ensure that the assembly phase (G1) ends before DNA synthesis (S) begins, thereby preventing re-initiation until the next cell cycle. More... »

PAGES

523-528

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ncb813

DOI

http://dx.doi.org/10.1038/ncb813

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1022202001

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12080347


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