Abstract

) The biochemical function of the BRCA1 tumor suppressor gene product is not understood. What little is known of how it operates suggests that it participates in the maintenance of genomic integrity. The protein is concentrated in nuclear foci (dots) in numerous cell lines and strains, and these structures also contain two, known BRCA1-associated proteins, BARD-1 and Rad 51. The function of the former is unknown; that of the latter is dedicated to proper strand exchange and certain other steps necessary for proper double strand break repair and homologous recombination. Nothing is known of why germ line BRCA1 mutations predispose affected individuals to the development of breast and/or ovarian cancer. An effort will be made to understand the biochemical significance of BRCA1 localization in nuclear dots; to search for and analyze the significance of its association with other BRCA1 binding proteins; to decipher the significance of the BRCA1/BARD1 interaction; to understand whether BRCA1 and Rad 51 interact directly or whether there are linker protein(s); and to analyze functional effects of Rad 51/BRCA1 complex formation.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA080111-04
Application #
6563945
Study Section
Subcommittee G - Education (NCI)
Project Start
2002-02-01
Project End
2003-01-31
Budget Start
Budget End
Support Year
4
Fiscal Year
2002
Total Cost
$291,807
Indirect Cost

  Institution

Name
Whitehead Institute for Biomedical Research
Department
Type
DUNS #
076580745
City
Cambridge
State
MA
Country
United States
Zip Code
02142

  Publications

Xiao, Tengfei; Li, Wei; Wang, Xiaoqing et al. (2018) Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. Proc Natl Acad Sci U S A 115:7869-7878
Zhang, Jinfang; Bu, Xia; Wang, Haizhen et al. (2018) Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance. Nature 553:91-95
Li, Andrew G; Murphy, Elizabeth C; Culhane, Aedin C et al. (2018) BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1? activation. Proc Natl Acad Sci U S A 115:E9600-E9609
Wu, Yanming; Zhang, Zhao; Cenciarini, Mauro E et al. (2018) Tamoxifen Resistance in Breast Cancer Is Regulated by the EZH2-ER?-GREB1 Transcriptional Axis. Cancer Res 78:671-684
Witwicki, Robert M; Ekram, Muhammad B; Qiu, Xintao et al. (2018) TRPS1 Is a Lineage-Specific Transcriptional Dependency in Breast Cancer. Cell Rep 25:1255-1267.e5
Jeselsohn, Rinath; Bergholz, Johann S; Pun, Matthew et al. (2018) Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations. Cancer Cell 33:173-186.e5
Hinohara, Kunihiko; Wu, Hua-Jun; Vigneau, Sébastien et al. (2018) KDM5 Histone Demethylase Activity Links Cellular Transcriptomic Heterogeneity to Therapeutic Resistance. Cancer Cell 34:939-953.e9
Wan, Lixin; Xu, Kexin; Wei, Yongkun et al. (2018) Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function. Mol Cell 69:279-291.e5
Dreijerink, Koen M A; Timmers, H T Marc; Brown, Myles (2017) Twenty years of menin: emerging opportunities for restoration of transcriptional regulation in MEN1. Endocr Relat Cancer 24:T135-T145
Rashidian, Mohammad; Ingram, Jessica R; Dougan, Michael et al. (2017) Predicting the response to CTLA-4 blockade by longitudinal noninvasive monitoring of CD8 T cells. J Exp Med 214:2243-2255

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