Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage.

Autor:	Hill SJ; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;, Rolland T; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Adelmant G; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Xia X; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Owen MS; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Dricot A; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Zack TI; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; The Broad Institute, Cambridge, Massachusetts 02142, USA;, Sahni N; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Jacob Y; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Département de Virologie, Unité de Génétique Moléculaire des Virus à ARN, Institut Pasteur, F-75015 Paris, France; UMR3569, Centre National de la Recherche Scientifique, F-75015 Paris, France; Unité de Génétique Moléculaire des Virus à ARN, Université Paris Diderot, F-75015 Paris, France;, Hao T; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, McKinney KM; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;, Clark AP; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA;, Reyon D; Molecular Pathology Unit, Center for Computational and Integrative Biology, Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA; Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;, Tsai SQ; Molecular Pathology Unit, Center for Computational and Integrative Biology, Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA; Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;, Joung JK; Molecular Pathology Unit, Center for Computational and Integrative Biology, Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA; Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA;, Beroukhim R; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; The Broad Institute, Cambridge, Massachusetts 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA., Marto JA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Vidal M; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Gaudet S; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Hill DE; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; Center for Cancer Systems Biology (CCSB), Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA;, Livingston DM; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA; Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA; david_livingston@dfci.harvard.edu.
Jazyk:	angličtina
Zdroj:	Genes & development [Genes Dev] 2014 Sep 01; Vol. 28 (17), pp. 1957-75.
DOI:	10.1101/gad.241620.114
Abstrakt:	BRCA1 is a breast and ovarian tumor suppressor. Given its numerous incompletely understood functions and the possibility that more exist, we performed complementary systematic screens in search of new BRCA1 protein-interacting partners. New BRCA1 functions and/or a better understanding of existing ones were sought. Among the new interacting proteins identified, genetic interactions were detected between BRCA1 and four of the interactors: TONSL, SETX, TCEANC, and TCEA2. Genetic interactions were also detected between BRCA1 and certain interactors of TONSL, including both members of the FACT complex. From these results, a new BRCA1 function in the response to transcription-associated DNA damage was detected. Specifically, new roles for BRCA1 in the restart of transcription after UV damage and in preventing or repairing damage caused by stabilized R loops were identified. These roles are likely carried out together with some of the newly identified interactors. This new function may be important in BRCA1 tumor suppression, since the expression of several interactors, including some of the above-noted transcription proteins, is repeatedly aberrant in both breast and ovarian cancers. (© 2014 Hill et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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