HCSGD entry for BRCA1

1. General information

Official gene symbolBRCA1
Entrez ID672
Gene full namebreast cancer 1, early onset
Other gene symbolsBRCAI BRCC1 BROVCA1 IRIS PNCA4 PPP1R53 PSCP RNF53
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

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3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0000151Ubiquitin ligase complexNAScellular_component
GO:0000724Double-strand break repair via homologous recombinationIDA TASbiological_process
GO:0000794Condensed nuclear chromosomeIEAcellular_component
GO:0001726RuffleIDAcellular_component
GO:0003677DNA bindingIEA TASmolecular_function
GO:0003684Damaged DNA bindingIEAmolecular_function
GO:0003713Transcription coactivator activityNASmolecular_function
GO:0003723RNA bindingIDAmolecular_function
GO:0004842Ubiquitin-protein ligase activityIDA IEAmolecular_function
GO:0005515Protein bindingIPImolecular_function
GO:0005634NucleusIDA IEAcellular_component
GO:0005654NucleoplasmTAScellular_component
GO:0005694ChromosomeISScellular_component
GO:0005737CytoplasmIEAcellular_component
GO:0005886Plasma membraneIDAcellular_component
GO:0005925Focal adhesionIDAcellular_component
GO:0006260DNA replicationIEAbiological_process
GO:0006281DNA repairIEA TASbiological_process
GO:0006301Postreplication repairIDAbiological_process
GO:0006302Double-strand break repairIMP TASbiological_process
GO:0006349Regulation of gene expression by genetic imprintingIEAbiological_process
GO:0006357Regulation of transcription from RNA polymerase II promoterTASbiological_process
GO:0006359Regulation of transcription from RNA polymerase III promoterTASbiological_process
GO:0006633Fatty acid biosynthetic processIEAbiological_process
GO:0006915Apoptotic processTASbiological_process
GO:0006974Cellular response to DNA damage stimulusTASbiological_process
GO:0006978DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediatorTASbiological_process
GO:0007059Chromosome segregationIMPbiological_process
GO:0007098Centrosome cycleIEAbiological_process
GO:0008270Zinc ion bindingIEAmolecular_function
GO:0008274Gamma-tubulin ring complexNAScellular_component
GO:0008630Intrinsic apoptotic signaling pathway in response to DNA damageIDAbiological_process
GO:0009048Dosage compensation by inactivation of X chromosomeIEAbiological_process
GO:0010212Response to ionizing radiationIMPbiological_process
GO:0015631Tubulin bindingNASmolecular_function
GO:0016567Protein ubiquitinationIDAbiological_process
GO:0019899Enzyme bindingIPImolecular_function
GO:0030521Androgen receptor signaling pathwayNASbiological_process
GO:0030529Ribonucleoprotein complexIDAcellular_component
GO:0031398Positive regulation of protein ubiquitinationIDAbiological_process
GO:0031436BRCA1-BARD1 complexIDAcellular_component
GO:0031572G2 DNA damage checkpointIMPbiological_process
GO:0031625Ubiquitin protein ligase bindingIPImolecular_function
GO:0031941Filamentous actinIDAcellular_component
GO:0034446Substrate adhesion-dependent cell spreadingIDAbiological_process
GO:0035066Positive regulation of histone acetylationIDAbiological_process
GO:0035067Negative regulation of histone acetylationIEAbiological_process
GO:0042127Regulation of cell proliferationTASbiological_process
GO:0042981Regulation of apoptotic processTASbiological_process
GO:0043009Chordate embryonic developmentIEAbiological_process
GO:0043234Protein complexIDAcellular_component
GO:0043627Response to estrogenIDAbiological_process
GO:0044030Regulation of DNA methylationIEAbiological_process
GO:0044212Transcription regulatory region DNA bindingIDA IEAmolecular_function
GO:0045717Negative regulation of fatty acid biosynthetic processIMPbiological_process
GO:0045739Positive regulation of DNA repairIMPbiological_process
GO:0045892Negative regulation of transcription, DNA-templatedIDAbiological_process
GO:0045893Positive regulation of transcription, DNA-templatedNAS TASbiological_process
GO:0045944Positive regulation of transcription from RNA polymerase II promoterIDA IEA IMPbiological_process
GO:0046600Negative regulation of centriole replicationNASbiological_process
GO:0050681Androgen receptor bindingNASmolecular_function
GO:0051571Positive regulation of histone H3-K4 methylationIDA IEAbiological_process
GO:0051572Negative regulation of histone H3-K4 methylationIEAbiological_process
GO:0051573Negative regulation of histone H3-K9 methylationIDA IEAbiological_process
GO:0051574Positive regulation of histone H3-K9 methylationIEAbiological_process
GO:0051865Protein autoubiquitinationIDAbiological_process
GO:0070512Positive regulation of histone H4-K20 methylationIDA IEAbiological_process
GO:0070531BRCA1-A complexIDAcellular_component
GO:0071158Positive regulation of cell cycle arrestIDAbiological_process
GO:0071681Cellular response to indole-3-methanolIDAbiological_process
GO:0085020Protein K6-linked ubiquitinationIDAbiological_process
GO:2000145Regulation of cell motilityIDAbiological_process
GO:2000617Positive regulation of histone H3-K9 acetylationIDA IEAbiological_process
GO:2000620Positive regulation of histone H4-K16 acetylationIDA IEAbiological_process
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.88706212910.00716465940.99999024730.1689194270

  • Individual experiment result
    ( "-" represent NA in the specific microarray platform )

Data sourceUp or downLog fold change
GSE11954Down-0.2738392017
GSE13712_SHEARUp0.3097568541
GSE13712_STATICUp0.1164427182
GSE19018Down-0.0697004033
GSE19899_A1Down-0.1791016916
GSE19899_A2Down-1.7897828157
PubMed_21979375_A1Down-0.3115389669
PubMed_21979375_A2Down-0.8882915692
GSE35957Down-1.1510307566
GSE36640Down-2.1274422575
GSE54402Down-0.2375121477
GSE9593Down-0.8076621376
GSE43922Down-0.6008577585
GSE24585Up0.0811438997
GSE37065Down-0.1848385609
GSE28863_A1Up0.1386111899
GSE28863_A2Up0.5996709181
GSE28863_A3Down-0.1561292257
GSE28863_A4Up0.2418693869
GSE48662Down-0.7407423498

5. Regulation relationships with compounds/drugs/microRNAs

  • Compounds

Not regulated by compounds

  • Drugs

Not regulated by drugs

  • MicroRNAs

  • mirTarBase

MiRNA_name

mirBase ID

miRTarBase ID

Experiment

Support type

References (Pubmed ID)

hsa-miR-146a-5pMIMAT0000449MIRT001920Luciferase reporter assayFunctional MTI18660546
hsa-miR-146a-5pMIMAT0000449MIRT001920Microarray//qRT-PCR//Western blotFunctional MTI19944095
hsa-miR-16-5pMIMAT0000069MIRT003328Luciferase reporter assayFunctional MTI19144710
hsa-miR-15a-5pMIMAT0000068MIRT003333Luciferase reporter assayFunctional MTI19144710
hsa-miR-212-3pMIMAT0000269MIRT003967MicroarrayFunctional MTI (Weak)17875710
hsa-miR-24-3pMIMAT0000080MIRT004836Luciferase reporter assay//Microarray//qRT-PCR//Western blotFunctional MTI19748357
hsa-miR-24-3pMIMAT0000080MIRT004836Reporter assay;Western blot;qRT-PCRFunctional MTI20018894
hsa-miR-193b-3pMIMAT0002819MIRT016496MicroarrayFunctional MTI (Weak)20304954
hsa-miR-335-5pMIMAT0000765MIRT018119Western blotFunctional MTI21618216
hsa-miR-215-5pMIMAT0000272MIRT024523MicroarrayFunctional MTI (Weak)19074876
hsa-miR-192-5pMIMAT0000222MIRT026534MicroarrayFunctional MTI (Weak)19074876
hsa-miR-21-5pMIMAT0000076MIRT030886MicroarrayFunctional MTI (Weak)18591254
hsa-miR-99b-3pMIMAT0004678MIRT038534CLASHFunctional MTI (Weak)23622248
hsa-miR-484MIMAT0002174MIRT042118CLASHFunctional MTI (Weak)23622248
hsa-miR-186-5pMIMAT0000456MIRT044906CLASHFunctional MTI (Weak)23622248
hsa-miR-181a-5pMIMAT0000256MIRT047335CLASHFunctional MTI (Weak)23622248
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  • mirRecord

MicroRNA name

mirBase ID

Target site number

MiRNA mature ID

Test method inter

MiRNA regulation site

Reporter target site

Pubmed ID

hsa-miR-146a-5pMIMAT0000449NAhsa-miR-146a19944095
hsa-miR-146a-5pMIMAT0000449NAhsa-miR-146a19944095
hsa-miR-24-3pMIMAT00000801hsa-miR-2419748357
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6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 19 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

27041576Here, we show that oncogenic Ras expression in human primary cells results in the downregulation of BRCA1 and 53BP1, two key factors in DNA DSB repair by homologous recombination and non-homologous end joining, respectively
27041576As a consequence, Ras-induced senescent cells are hindered in their ability to recruit BRCA1 and 53BP1 to DNA damage sites
27041576Whereas BRCA1 is downregulated at transcripts levels, 53BP1 loss is caused by activation of cathepsin L-mediated degradation of 53BP1 protein
26106036Haploinsufficiency for BRCA1 leads to cell-type-specific genomic instability and premature senescence
26106036Although BRCA1 function is essential for maintaining genomic integrity in all cell types, it is unclear why increased risk of cancer in individuals harbouring deleterious mutations in BRCA1 is restricted to only a select few tissues
26106036These results identify a novel form of cellular senescence and provide a potential molecular basis for the rapid cell- and tissue- specific predisposition of breast cancer development associated with BRCA1 haploinsufficiency
25582120BRCA1 and CtIP promote alternative non-homologous end-joining at uncapped telomeres
25582120Here, we show that the tumour suppressor BRCA1, together with its interacting partner CtIP, both acting in end resection, also promotes end-joining of uncapped telomeres
25582120BRCA1 and CtIP do not function in the ATM-dependent telomere damage signalling, nor in telomere overhang removal, which are critical for telomere fusions by C-NHEJ
25582120Instead, BRCA1 and CtIP act in the same pathway as LIG3 to promote joining of de-protected telomeres by A-NHEJ
25582120Our work therefore ascribes novel roles for BRCA1 and CtIP in end-processing and fusion reactions at uncapped telomeres, underlining the complexity of DNA repair pathways that act at chromosome ends lacking protective structures
25119968S4 and S3R cells have the same level of p70 nibrin, however p70 from S4 cells was able to form more complexes with ATM and BRCA1
23673322Chromatin remodeling, BRCA1, SAHF and cellular senescence
23438604BRG1 is required for formation of senescence-associated heterochromatin foci induced by oncogenic RAS or BRCA1 loss
23438604We have previously reported that both oncogene-induced dissociation of BRCA1 from chromatin and BRCA1 knockdown itself drive senescence by promoting formation of senescence-associated heterochromatin foci (SAHF)
23438604However, the molecular mechanism by which BRCA1 regulates SAHF formation and senescence is unclear
23438604BRG1 is a chromatin-remodeling factor that interacts with BRCA1 and pRB
23438604Here we show that BRG1 is required for SAHF formation and senescence induced by oncogenic RAS or BRCA1 loss
23438604The interaction between BRG1 and BRCA1 is disrupted during senescence
23438604BRG1 knockdown suppresses the formation of SAHF and senescence, while it has no effect on BRCA1 chromatin dissociation induced by oncogenic RAS, indicating that BRG1 functions downstream of BRCA1 chromatin dissociation
23438604Furthermore, BRG1 knockdown inhibits SAHF formation and senescence induced by BRCA1 knockdown
23438604Together, these studies reveal the molecular underpinning by which BRG1 acts downstream of BRCA1 to promote SAHF formation and senescence
22751483RAS, cellular senescence and transformation: the BRCA1 DNA repair pathway at the crossroads
22751483Here, we discuss our recent evidence that RAS-induced suppression of DNA repair response via dissociation of BRCA1 from chromatin promotes senescence while predisposing cells to senescence bypass and transformation by allowing for secondary hits
22258036Furthermore, DNA methylation levels of genes related to development of most or all tumor types, such as BRCA1, CCNA1, CDKN2A (p16), THBS1, TNFRSF10C and TNFRSF10D, were increased in BPA-exposed HMEC
22019631In this review the tumor suppressor genes p53, FoxO, retinoblastoma (RB), p21, p16, and breast cancer susceptibility genes 1 and 2 (BRCA1 and BRCA2) and their roles in oxidative stress are summarized with a focus on the links and interplay between their pathways and reactive oxygen species (ROS)
21173253The most statistically significant classes of differentially expressed genes included p53 signaling, G2/M checkpoint regulation, and genes involved in the role of BRCA1 in the DNA damage response
19938640Breast cancer susceptibility gene (BRCA1) is a nuclear phosphoprotein expressed in many nuclear processes, including stem cell regulator, DNA damage repair, recombination, transcription, ubiquitination, cell cycle checkpoint enforcement, and centrosome regulation
19938640Several molecular targeting therapies are described by activation and blocking distinct developmental signaling cascade elements, such as BRCA1, EGFR, hedgehog, Wnt/beta-catenin, and/or Notch pathways, which are frequently upregulated in cancer progenitor cells during the initiation and development of breast cancer
19836377Cancers with nonfunctional BRCA1 and BRCA2 are particularly sensitive to combined treatment with DNA damaging drugs and inhibitors of poly(ADP-ribose) polymerase
19716796A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency
19716796Using mouse embryonic fibroblasts with constitutively increased DNA damage due to the absence of the full-length form of the tumor suppressor Brca1 (Brca1(Delta 11/Delta 11)), we show that deletion of p53 binding protein 1 (53BP1) selectivity abrogates senescence and cell death stimulated by reduced Brca1 activity
19716796Furthermore, the embryonic lethality induced by Brca1 mutation can be alleviated by 53BP1 deletion
19716796Together, these in vitro and in vivo data suggest that 53BP1 is specifically required for the development of premature senescence and apoptosis induced by Brca1 deficiency
19372557Premature senescence is a major response to DNA cross-linking agents in BRCA1-defective cells: implication for tailored treatments of BRCA1 mutation carriers
19372557Nevertheless, tailored treatments for BRCA1 mutation carriers have only been partially investigated up to now
19372557In this study, we took advantage of the RNA interference technology to generate a series of partially transformed (HBL100) and tumorigenic (MCF7 and T47D) breast cancer cell lines in which BRCA1 expression was silenced at different levels
19372557Our models confirmed the peculiar sensitivity to interstrand cross-link inducers associated with BRCA1 deficiency
19372557Overall, our results support a role for BRCA1 in the regulation of interstrand cross-link-induced premature senescence and suggest a reconsideration of the therapeutic power of mitomycin/platinum-based treatments in BRCA1 carriers
18001825We have shown that RNF8 facilitates the accumulation of checkpoint mediator proteins BRCA1 and 53BP1 to the damaged chromatin, on one hand through the phospho-dependent FHA domain-mediated binding of RNF8 to MDC1, on the other hand via its role in ubiquitylating H2AX and possibly other substrates at damage sites
17996922Moreover, increased SIRT1 expression was associated with the downregulation of endogenous WRN and a decreased frequency of cells with BRCA1 foci
17700066The higher load of DNA damage may also contribute to cancer predisposition in families with inherited heterozygous defects in the DDR barrier, such as in ATM, BRCA1, BRCA2, p53 and other genes
15781639The TBX2 gene encoding a key developmental transcription factor is amplified in pancreatic cancer cell lines and preferentially amplified and overexpressed in BRCA1 and BRCA2 mutated breast tumors
12533509Senescence, aging, and malignant transformation mediated by p53 in mice lacking the Brca1 full-length isoform
12533509Here we provide evidence to support this theory by showing that the absence of the Brca1 full-length isoform causes senescence in mutant embryos and cultured cells as well as aging and tumorigenesis in adult mice
12533509These observations provide the first in vivo evidence that links cell senescence to aging due to impaired function of Brca1 at the expense of tumorigenesis
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