Distinct roles for cyclins E and A during DNA replication complex assembly and activation.
Nat Cell Biol
; 4(7): 523-8, 2002 Jul.
Article
em En
| MEDLINE
| ID: mdl-12080347
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ciclina A
/
Ciclina E
/
Replicação do DNA
Limite:
Humans
Idioma:
En
Ano de publicação:
2002
Tipo de documento:
Article