ABSTRACT Much of the predisposition to hereditary breast and ovarian cancer has been attributed to inherited defects in the _BRCA1_ tumour-suppressor gene1,2,3. The nuclear protein BRCA1 has

the properties of a transcription factor4,5,6,7, and can interact with the recombination and repair protein RAD51 (ref. 8). Young women with germline alterations in _BRCA1_ develop breast

cancer at rates 100-fold higher than the general population3, and _BRCA1_-null mice die before day 8 of development9,10. However, the mechanisms of _BRCA1_-mediated growth regulation and

tumour suppression remain unknown. Here we show that BRCA1 transactivates expression of the cyclin-dependent kinase inhibitor p21WAF1/CIP1 in a p53-independent manner, and that BRCA1

contributes to cell-cycle arrest and growth suppression is through the induction of p21. Access through your institution Buy or subscribe This is a preview of subscription content, access

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Β-CATENIN-INDUCED LETHALITY IN BRCA1/2-DEFICIENT CELLS Article Open access 13 August 2021 PATHOGENIC _BRCA1_ VARIANTS DISRUPT PLK1-REGULATION OF MITOTIC SPINDLE ORIENTATION Article Open

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This work was supported by grants from the NIH and the Breast Cancer Research Foundation to B.L.W. W.S.E.-D. is an assistant investigator of the Howard Hughes Medical Institute. AUTHOR

INFORMATION Author notes * Kumaravel Somasundaram and Hongbing Zhang: These authors contributed equally to this study. AUTHORS AND AFFILIATIONS * Laboratory of Molecular Oncology and Cell

Cycle Regulation, Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA Kumaravel Somasundaram, Yi-Xin Zeng, Gen Sheng Wu 

& Wafik S. El-Deiry * Departments of Medicine, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA Kumaravel Somasundaram, Hongbing Zhang, Yi-Xin Zeng, 

Yi Peng, Hongxiang Zhang, Gen Sheng Wu, Barbara L. Weber & Wafik S. El-Deiry * Departments of Genetics, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania,

USA Barbara L. Weber & Wafik S. El-Deiry * Departments of Cancer Center, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA Barbara L. Weber & 

Wafik S. El-Deiry * Brookdale Center for Developmental and Molecular Biology and Department of Medicine, The Mount Sinai School of Medicine, New York, 10029, New York, USA Yariv Houvras 

& Jonathan D. Licht Authors * Kumaravel Somasundaram View author publications You can also search for this author inPubMed Google Scholar * Hongbing Zhang View author publications You

can also search for this author inPubMed Google Scholar * Yi-Xin Zeng View author publications You can also search for this author inPubMed Google Scholar * Yariv Houvras View author

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author publications You can also search for this author inPubMed Google Scholar * Gen Sheng Wu View author publications You can also search for this author inPubMed Google Scholar *

Jonathan D. Licht View author publications You can also search for this author inPubMed Google Scholar * Barbara L. Weber View author publications You can also search for this author

inPubMed Google Scholar * Wafik S. El-Deiry View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Wafik S. El-Deiry.

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Somasundaram, K., Zhang, H., Zeng, YX. _et al._ Arrest of the cell cycle by the tumour-suppressor BRCA1

requires the CDK-inhibitor p21WAF1/CiPl. _Nature_ 389, 187–190 (1997). https://doi.org/10.1038/38291 Download citation * Received: 09 July 1997 * Accepted: 28 July 1997 * Issue Date: 11

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