Systematic screening reveals a role for BRCA1 in the response to transcription-associated DNA damage
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2014
- Source ID
- 10.1101/gad.241620.114
Entities
People
- Allison P. Clark
- Amélie Dricot
- David E. Hill
- David M. Livingston
- Deepak Reyon
- Guillaume Adelmant
- J. Keith Joung
- Jarrod A. Marto
- Kristine M. Mckinney
- Marc Vidal
- Matthew S. Owen
- Nidhi Sahni
- Rameen Beroukhim
- Sarah J. Hill
- Shengdar Q. Tsai
- Suzanne Gaudet
- Thomas Rolland
- Tong Hao
- Travis I. Zack
- Xianfang Xia
- Yves Jacob
Organizations
- National Cancer Institute
- National Human Genome Research Institute
- National Institute of Neurological Disorders and Stroke
- National Institutes of Health
- Susan G. Komen for the Cure
- United States Department of Defense