Regulation of the BRCA1 gene by an SRC3/53BP1 complex
1 Department of Oncology, London Regional Cancer Program and the Lawson Health Research Institute, 790 Commissioners Rd, London, Ontario N6A 4L6 Canada
2 Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario N6G 2V4 Canada
3 Department of Physiology and Pharmacology, Siebens-Drake Medical Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario N6G 2V4 Canada
BMC Biochemistry 2011, 12:50 doi:10.1186/1471-2091-12-50Published: 13 September 2011
Steroid Receptor coactivator 3(SRC3) is an oncogene and a member of the SRC family of nuclear receptor coactivator proteins that mediate the transcriptional effects of nuclear hormone receptors as well as other transcription factors.
We have used protein purification and mass spectrometry to identify the 53BP1 tumour suppressor as a novel SRC3-associated protein. Copurification was demonstrated using multiple antibodies, and was not dependent on DNA damage suggesting that SRC3 is not directly involved in the DNA damage response. However using chromatin immunoprecipitation(ChIP) and siRNA knockdown, we have demonstrated that both SRC3 and 53BP1 co-occupy the same region of the BRCA1 promoter and both are required for BRCA1 expression in HeLa cells.
Our results suggest that both 53BP1 and SRC3 have a common function that converge at the BRCA1 promoter and possibly other genes important for DNA repair and genomic stability.