An Early S Phase Checkpoint Is Regulated by the E2F1 Transcription Factor

The E2F1 transcription factor regulates transit of cells through the S phase checkpoint, dependent on its association with cyclin A/cdk2. Expression in cells of a mutant E2F1 lacking the cyclin A/cdk2 binding domain leads to partial arrest of cells at the S phase checkpoint. When subconfluent growin...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1999-04, Vol.258 (1), p.77-80
Main Authors: Stubbs, Matthew C., Strachan, Gordon D., Hall, David J.
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Carrier Proteins
Cell Cycle Proteins
DNA - metabolism
DNA-Binding Proteins
E2F Transcription Factors
E2F1 Transcription Factor
Mice
Retinoblastoma-Binding Protein 1
S Phase - physiology
Thymidine - metabolism
Transcription Factor DP1
Transcription Factors - physiology
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Summary:The E2F1 transcription factor regulates transit of cells through the S phase checkpoint, dependent on its association with cyclin A/cdk2. Expression in cells of a mutant E2F1 lacking the cyclin A/cdk2 binding domain leads to partial arrest of cells at the S phase checkpoint. When subconfluent growing cells expressing this mutant E2F1 are analyzed in detail, it is shown here that they display a significantly reduced incorporation of3H-thymidine into the DNA of each S phase cell, compared to control cells or to cells overexpressing full-length E2F1. Further, when cells are blocked at the G1/S phase border and released, there is a clear reduction in the amount of3H-thymidine incorporated into the DNA of S phase cells by 1.5 hours post release. Considering a normal 6 hour S phase duration, the results show that the S phase checkpoint mediated by E2F1 is not a late S phase event but an early one.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1999.0603