Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage
Year: 2014
Type: preprint
Abstract: 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.
Source: Genes & Development
Authors: Sarah J. Hill, Thomas Rolland, Guillaume Adelmant, Xianfang Xia, Matthew S. Owen, Amélie Dricot, Travis I. Zack, Nidhi Sahni, Yves Jacob, Tong Hao, Kristine M. McKinney, Allison P. Clark, Deepak Reyon, Shengdar Q. Tsai, J. Keith Joung, Rameen Beroukhim, Jarrod A. Marto, Marc Vidal, Suzanne Gaudet, David E. Hill, David M. Livingston
Institutions: Harvard University, Dana-Farber Cancer Institute, Broad Institute, Centre National de la Recherche Scientifique, Institut Pasteur, Department of Virology, Université Paris Diderot, Massachusetts General Hospital, Center for Computational and Integrative Biology, Massachusetts General Hospital, Dana-Farber/Harvard Cancer Center
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
Funders: U.S. Department of Defense, Susan G. Komen for the Cure, Breast Cancer Research Foundation, Massachusetts General Hospital, Honorable Tina Brozman Foundation, Dana-Farber/Harvard Cancer Center, National Institutes of Health, National Human Genome Research Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Neurological Disorders and Stroke, National Center for Chronic Disease Prevention and Health Promotion
Awards: G2163469858, G2202258210, Mapping the Human Binary Interactome Network, G318341812, G340051698, Molecular analysis of the function of BRCA1-TONSL complexes, G3902606194, G4119534169, G4258809411, Broad Institute Center for Cancer Systems Biology, G5728525287, G5850682332, Molecular Mechanisms of Fate Choice in Neural Stem Cells (P01), G707340384, G7306691104, G7715776597, G8658596978, G9000052266, G9000149830, G9000325665
OpenAlex ID: W2005453713