Regulation of the BRCA1 Gene by an SRC3/53BP1 Complex

Authors

Dale Corkery, The University of Western Ontario
Gobi Thillainadesan, The University of Western Ontario
Niamh Coughlan, The University of Western Ontario
Ryan D. Mohan, The University of Western Ontario
Majdina Isovic, The University of Western Ontario
Marc Tini, The University of Western Ontario
Joseph Torchia, The University of Western Ontario

Document Type

Article

Publication Date

9-13-2011

Journal

BMC Biochemistry

Volume

12

Issue

50

URL with Digital Object Identifier

http://dx.doi.org/10.1186/1471-2091-12-50

Abstract

BACKGROUND: 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.

RESULTS: 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.

CONCLUSIONS: 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.