BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A

Abstract

The breast cancer specific tumour suppressor protein, BRCA1 (refs 1,2), activates transcription when linked with a DNA-binding domain3,4 and is a component of the RNA polymerase II (Pol II) holoenzyme5,6. We show here that RNA helicase A (RHA) protein7,8 links BRCA1 to the holoenzyme complex. The region of BRCA1 which interacts with RHA and, thus, the holoenzyme complex, corresponds to subregions of the BRCT domain of BRCA1 ( ref. 9). This interaction was shown to occur in yeast nuclei, and expression in human cells of a truncated RHA molecule which retains binding to BRCA1 inhibited transcriptional activation mediated by the BRCA1 carboxy terminus. These data are the first to identify a specific protein interaction with the BRCA1 C-terminal domain and are consistent with the model that BRCA1 functions as a transcriptional coactivator.

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Figure 1: RHA binds the C-terminal domain of BRCA1 in vitro.
Figure 2: BRCA1 interaction with RHA in vitro.
Figure 3: Transcription activation by GBD-BRCA1 C-terminus is inhibited by truncated RHA protein.

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Acknowledgements

We thank A. Monteiro and H. Hanafusa for the kind gift of GBD-BRCA1 constructs, and we thank M. Montminy, A. Dutta and D. Haile for helpful advice during the course of these experiments. This work was supported in part by NIH grant GM53504, a Junior Faculty Research Award from the American Cancer Society and also a Massachusetts Dept. of Public Health Breast Cancer Research Program grant to J.D.P. S.F.A. is supported by NRSA GM18829 from the NIH, and T.N. is supported by the Uehara Memorial Foundation and by the Otsuka Pharmaceutical Company.

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Correspondence to Jeffrey D. Parvin.

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Anderson, S., Schlegel, B., Nakajima, T. et al. BRCA1 protein is linked to the RNA polymerase II holoenzyme complex via RNA helicase A. Nat Genet 19, 254–256 (1998). https://doi.org/10.1038/930

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