Breast Cancer Res Treat
Departments of Oncology and Human Genetics, Program in Cancer Genetics, McGill University, Montreal, QC, Canada H2W 1S6.
Published: September 2009
Background Around half of familial breast cancer cases are caused by germ-line mutations in genes which are critically involved in the maintenance of genome stability. Mutations in related genes functioning in DNA repair may account for currently unattributed cases. Two such genes, RAP80 and Abraxas, have recently been identified to be in a complex with BRCA1, and are required for the localization of BRCA1 to DNA damage foci. Methods RAP80 and Abraxas variants were screened for in a cohort of 95 high risk, non-BRCA1/2 breast cancer cases of varying ethnicity: those of Ashkenazi Jewish (n = 35), mixed Canadian (n = 34) and Swiss descent (n = 26). Results We have identified four missense variants, four silent SNPs, three SNPs in the UTRs and seven intronic variants in RAP80. Two of the previously reported RAP80 variants were further investigated. In Abraxas, we have identified two missense, nine intronic and two variants in the 3' UTR. Conclusions Overall, it seems unlikely that moderate to highly penetrant alleles of either RAP80 or Abraxas, confer a significantly high relative risk of breast cancer.
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http://dx.doi.org/10.1007/s10549-008-0134-y | DOI Listing |
Genes Dev
December 2019
Department of Genetics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
The establishment of polyubiquitin conjugates with distinct linkages play important roles in the DNA damage response. Much remains unknown about the regulation of linkage-specific ubiquitin signaling at sites of DNA damage. Here we reveal that Cezanne (also known as Otud7B) deubiquitinating enzyme promotes the recruitment of Rap80/BRCA1-A complex by binding to Lys63-polyubiquitin and targeting Lys11-polyubiquitin.
View Article and Find Full Text PDFMol Cell
August 2019
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; University of Basel, Petersplatz 10, 4003 Basel, Switzerland. Electronic address:
In mammals, ∼100 deubiquitinases act on ∼20,000 intracellular ubiquitination sites. Deubiquitinases are commonly regarded as constitutively active, with limited regulatory and targeting capacity. The BRCA1-A and BRISC complexes serve in DNA double-strand break repair and immune signaling and contain the lysine-63 linkage-specific BRCC36 subunit that is functionalized by scaffold subunits ABRAXAS and ABRO1, respectively.
View Article and Find Full Text PDFNat Commun
June 2017
Research Center for Translational Medicine, East Hospital, Tongji University School of Medicine, Shanghai 200120, China.
BRCA1 regulates multiple cellular pathways that maintain genomic stability including cell cycle checkpoints, DNA repair, protein ubiquitination, chromatin remodelling, transcriptional regulation and apoptosis. Receptor-associated protein 80 (RAP80) helps recruit BRCA1 to double-strand breaks (DSBs) through the scaffold protein CCDC98 (Abraxas) and facilitates DNA damage response (DDR). However, the regulation of RAP80-BRCA1 complex is still unclear.
View Article and Find Full Text PDFCancer Sci
October 2016
Department of Translational Oncology, St. Marianna University Graduate School of Medicine, Kawasaki, Japan.
The breast and ovarian cancer predisposition protein BRCA1 forms three mutually exclusive complexes with Fanconi anemia group J protein (FANCJ, also called BACH1 or BRIP1), CtIP, and Abraxas/RAP80 through its BRCA1 C terminus (BRCT) domains, while its RING domain binds to BRCA1-associated RING domain 1 (BARD1). We recently found that the interaction between heterochromatin protein 1 (HP1) and BARD1 is required for the accumulation of BRCA1 and CtIP at sites of DNA double-strand breaks. Here, we investigated the importance of HP1 and BARD1-HP1 interaction in the localization of FANCJ together with the other BRCA1-BRCT binding proteins to clarify the separate role of the HP1-mediated pathway from the RNF8/RNF168-induced ubiquitin-mediated pathway for BRCA1 function.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
July 2016
Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, Republic of Korea Center for Neuroscience Imaging Research, Institute for Basic Science (IBS), Sungkyunkwan University, Suwon 440-746, Republic of Korea
Sustaining genomic integrity is essential for preventing onset of cancers. Therefore, human cells evolve to have refined biological pathways to defend genetic materials from various genomic insults. DNA damage response and DNA repair pathways essential for genome maintenance are accomplished by cooperative executions of multiple factors including breast cancer type 1 susceptibility protein (BRCA1).
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