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, 83 (7), 1149-58

Cyclin A-kinase Regulation of E2F-1 DNA Binding Function Underlies Suppression of an S Phase Checkpoint

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Cyclin A-kinase Regulation of E2F-1 DNA Binding Function Underlies Suppression of an S Phase Checkpoint

W Krek et al. Cell.

Abstract

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-1DNA 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 or apoptosis, depending upon whether the 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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