Cyclin A-kinase regulation of E2F-1 DNA binding function underlies suppression of an S phase checkpoint
W Krek, G Xu, DM Livingston - Cell, 1995 - cell.com
W Krek, G Xu, DM Livingston
Cell, 1995•cell.comCommitment of mammalian cells to enter S phase enables the transcription factor E2F-1 to
activate certain genes whose products mediate cell cycle advance. In S phase, E2F-1 forms
stable complexes with cyclin A-kinase, which in turn eliminates E2F-1 DNA binding function.
Here, we show that suppression of E2F-1 DNA-binding activity by cyclin A-kinase is linked to
orderly S phase progression. Disruption of this linkage resulted in S phase delay/arrest
followed by regrowth orapoptosis, depending upon whetherthe DNA-bound E2F-1 could …
activate certain genes whose products mediate cell cycle advance. In S phase, E2F-1 forms
stable complexes with cyclin A-kinase, which in turn eliminates E2F-1 DNA binding function.
Here, we show that suppression of E2F-1 DNA-binding activity by cyclin A-kinase is linked to
orderly S phase progression. Disruption of this linkage resulted in S phase delay/arrest
followed by regrowth orapoptosis, depending upon whetherthe DNA-bound E2F-1 could …
Summary
Commitment of mammalian cells to enter S phase enables the transcription factor E2F-1 to activate certain genes whose products mediate cell cycle advance. In S phase, E2F-1 forms stable complexes with cyclin A-kinase, which in turn eliminates E2F-1 DNA binding function. Here, we show that suppression of E2F-1 DNA-binding activity by cyclin A-kinase is linked to orderly S phase progression. Disruption of this linkage resulted in S phase delay/arrest followed by regrowth orapoptosis, depending upon whetherthe DNA-bound E2F-1 could transactivate. Hence, the unscheduled presence of E2F-1 on specific DNA sequences during S phase can activate a specific S phase checkpoint, thereby linking transcription, DNA replication, and cell cycle control.
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