期刊
GENES & DEVELOPMENT
卷 28, 期 17, 页码 1957-1975出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.241620.114
关键词
BRCA1 interaction screening; DNA damage; transcription
资金
- Department of Defense Breast Cancer Research Program Fellowship [W81XWH-08-1-0748]
- National Cancer Institute (NCI) Fellowship [1F30CA167895-01]
- Breast Cancer Research Foundation
- Susan G. Komen Foundation for the Cure [SAC110022]
- NCI SPORE grant in breast cancer research [P50CA089393]
- NCI [R01 (R01CA136512), P01 (P01CA080111)]
- National Institutes of Health (NIH) Director's Pioneer Award [DP1 GM105378]
- Jim and Ann Orr Massachusetts General Hospital Research Scholar Award
- National Institute of Neurological Disorders and Stroke [P01NS047572]
- Dana-Farber Cancer Institute Strategic Research Initiative
- Susan Smith Center for Women's Cancers
- Honorable Tina Brozman Foundation
- National Human Genome Research Institute grant [R01HG001715]
- NCI grant [U54CA112962]
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.
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