p300/CREB-binding protein interacts with ATR and is required for the DNA replication checkpoint.
The highly related acetyltransferases, p300 and CREB-binding protein (CBP) are coactivators of signal-responsive transcriptional activation. In addition, recent evidence suggests that p300/CBP also interacts directly with complexes that mediate DNA replication and repair. In this report, we show that loss of p300/CBP in mammalian cells results in a defect in the cell cycle arrest induced by stalled DNA replication. We demonstrate that complexes containing p300/CBP and ATR can be detected in mammalian cells, and that the downstream kinase CHK1 fails to be phosphorylated in response to stalled DNA replication in cells that lack p300/CBP. These observations broaden the roles for the p300/CBP acetyltransferases to include the modulation of chromatin structure and function during DNA metabolic events as well as for transcription.
Stauffer
Daniel
D
Department of Biochemistry, Oregon Health and Sciences University, Portland, Oregon 97201.
Chang
Bill
B
Department of Biochemistry, Oregon Health and Sciences University, Portland, Oregon 97201.
Huang
Jing
J
Department of Biochemistry, Oregon Health and Sciences University, Portland, Oregon 97201.
Dunn
Andrew
A
Department of Biochemistry, Oregon Health and Sciences University, Portland, Oregon 97201.
Thayer
Mathew
M
Department of Biochemistry, Oregon Health and Sciences University, Portland, Oregon 97201. Electronic address: thayerm@ohsu.edu.
D064007:Ataxia Telangiectasia Mutated Proteins; D050882:CREB-Binding Protein / Q000378:metabolism* / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism* / Q000502:physiology; D004261:DNA Replication / Q000502:physiology*; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism* / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism* / Q000502:physiology; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D064007:Ataxia Telangiectasia Mutated Proteins; D050882:CREB-Binding Protein; D018797:Cell Cycle Proteins; D051548:Histone Acetyltransferases; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C576597:ATR protein, human