BRCA1 interacts with components of the histone deacetylase complex.
Germ-line mutations in the BRCA1 tumor-suppressor gene are associated with an increased susceptibility to breast and ovarian cancer. BRCA1 contains a carboxyl-terminal domain (BRCT) that is shared with several other proteins involved in maintaining genome integrity. In an effort to understand the function of BRCA1, we sought to isolate proteins that interact with the BRCT domain. Purified BRCT polypeptide was used as a probe to screen a human placenta cDNA expression library by Far Western analysis. Here we report that BRCA1 interacts in vivo and in vitro with the Rb-binding proteins, RbAp46 and RbAp48, as well as with Rb. Moreover, the BRCT domain associates with the histone deacetylases HDAC1 and HDAC2. These results demonstrate that BRCA1 interacts with components of the histone deacetylase complex, and therefore may explain the involvement of BRCA1 in multiple processes such as transcription, DNA repair, and recombination.
Yarden
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RI
Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Brody
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LC
D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D006367:HeLa Cells; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding / Q000235:genetics; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D015533:Transcriptional Activation
D019313:BRCA1 Protein; D002352:Carrier Proteins; D009687:Nuclear Proteins; C082637:RBBP4 protein, human; C490746:RBBP7 protein, human; C489969:Rbbp4 protein, mouse; D056505:Retinoblastoma-Binding Protein 4; D056524:Retinoblastoma-Binding Protein 7; D006655:Histone Deacetylases