Investigating the role of 53BP1 in regulating gene transcription.

Abstract

53BP1 is a DNA damage responsive protein that plays a crucial role in checkpoint activation and DNA repair. In addition to its involvement in the cellular response to DNA damage, it has been suggested that 53BP1 can also function to regulate gene expression. 53BP1 was originally identified in a yeast two-hybrid screen for novel modulators of p53 transcriptional activity. Despite this, the role of 53BP1 in transcriptional regulation remains poorly understood.
To investigate the effect of 53BP1 on cellular transcription, a microarray approach was utilised to study the gene expression patterns in cells treated with and without 53BP1 siRNA, before and after ionising radiation. Microarray analysis identified numerous genes whose expression was regulated by 53BP1 in the absence and presence of DNA damage. These data suggest that 53BP1 functions as a transcriptional regulator. In support of this, in vitro and in vivo studies have shown that 53BP1 binds to the transcriptional co-activators, CBP and p300. These findings indicate that the binding of 53BP1 to CBP and p300 may be facilitating its role as a regulator of transcription.