Disease relevance of BRIP1

• Using genetic mapping, mutation identification and western-blot data, we identify the defective protein in FA-J cells as BRIP1 (also called BACH1), a DNA helicase that is a binding partner of the breast cancer tumor suppressor BRCA1 [1].
• Moreover, in human cells exposed to mitomycin C, short interfering RNA-mediated knock-down of BRIP1 leads to a substantial increase in chromosome aberrations, a characteristic phenotype of cells derived from individuals with Fanconi anemia [2].
• Previously, two BACH1 germ line missense mutations have been identified in early-onset breast cancer patients with and without family history of breast and ovarian cancer [3].
• The transcription factor Bach1 is a member of a novel family of broad complex, tramtrack, bric-a-brac/poxvirus and zinc finger (BTB/POZ) basic region leucine zipper factors [4].
• Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas [5].
• Herein, we report a novel BRIP1 germ-line mutation identified in a woman with early-onset breast cancer [6].

Psychiatry related information on BRIP1

• Aromatherapy, Bach flower remedies, hypnotherapy, massage, nutrition, reflexology, Reiki and yoga were all recommended as suitable treatments for stress/anxiety [7].
• The current study extended previous research by Bach and Hayes (2002. The use of Acceptance and Commitment Therapy to prevent the rehospitalization of psychotic patients: A randomized controlled trial. Journal of Consulting and Clinical Psychology, 70, 1129-1139) using Acceptance and Commitment Therapy (ACT) in the treatment of psychosis [8].

High impact information on BRIP1

• Biallelic BRIP1 mutations were recently shown to cause Fanconi anemia complementation group J. Thus, inactivating truncating mutations of BRIP1, similar to those in BRCA2, cause Fanconi anemia in biallelic carriers and confer susceptibility to breast cancer in monoallelic carriers [9].
• Truncating mutations in the Fanconi anemia J gene BRIP1 are low-penetrance breast cancer susceptibility alleles [9].
• The BRCA1-interacting helicase BRIP1 is deficient in Fanconi anemia [1].
• We cloned the chicken ortholog of BRIP1 and established a homozygous knockout in the avian B-cell line DT40 [2].
• The phenotype of these brip1 mutant cells in response to DNA damage differs from that of brca1 mutant cells and more closely resembles that of fancc mutant cells, with a profound sensitivity to the DNA-crosslinking agent cisplatin and acute cell-cycle arrest in late S-G2 phase [2].

Chemical compound and disease context of BRIP1

• On "The effect of intravenous lidocaine on nociceptive processing in diabetic neuropathy" by Bach et al. in Pain, 40 (1990) 29-34 [10].
• The Bach model was developed to predict the absolute 10-year risk of developing lung cancer among smokers by use of participants in the Carotene and Retinol Efficacy Trial of lung cancer prevention [11].
• We assessed the validity of the Bach model among 6239 smokers from the placebo arm of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. The expected numbers of lung cancer cases and deaths without lung cancer were calculated from the Bach model and compared with the observed numbers of corresponding events over 10 years [11].

Biological context of BRIP1

• Of 25 variants identified in BRIP1, in addition to four common silent or missense mutations, we identified Gln540Leu, a non-conservative amino acid change, in a single familial proband with inflammatory breast cancer, but this mutation was not present in her three relatives with breast cancer [12].
• Haplotype analysis suggests that all ZBRK1 SNPs fall within a single block with two SNPs capturing 92% of the haplotype diversity, while the BRIP1 SNPs fall in two blocks, with five SNPs capturing 89% of the haplotype diversity [12].
• Mutations within the BRCT repeats disrupt the interaction between BRCA1 and BACH1, lead to defects in DNA repair, and result in breast and ovarian cancer [13].
• The protein predicted to be defective in individuals with Fanconi anemia complementation group J (FA-J), FANCJ, is a missing component in the Fanconi anemia pathway of genome maintenance [14].
• We have investigated the DNA substrate specificity of BACH1 (BRCA1-associated C-terminal helicase) [15].

Anatomical context of BRIP1

• RESULTS: Six BACH1 germ line alterations were observed in the mutation analysis, but none of these were found to associate with the cancer phenotype [3].
• Moreover, we identified a homozygous nonsense mutation in BACH1 in a FA-J patient-derived cell line and could not detect BACH1 protein in this cell line [16].
• Here we describe the gene structure of human BACH1, including a newly identified promoter and an alternatively RNA-spliced truncated form of BACH1, designated BACH1t, abundantly transcribed in human testis [4].
• Whereas expression of Bach1 appears ubiquitous, that of Bach2 is restricted to monocytes and neuronal cells [17].
• The contact of fibrin with the apical surface of human umbilical vein endothelial cells (HUVEC) can induce capillary tube formation via the interaction of fibrin beta15-42 with a putative cell receptor (Chalupowicz, D. G., Chowdhury, Z. A., Bach, T. L., Barsigian, C., and Martinez, J. (1995) J. Cell Biol. 130, 207-215) [18].

Associations of BRIP1 with chemical compounds

• The phosphorylated serine 990 and phenylalanine 993 of BACH1 anchor the binding to BRCA1 through specific interactions with a surface cleft at the junction of the two BRCT repeats [19].
• Using a glutathione-S-transferase (GST) pull-down assay with murine cells, we isolated only one major BRCA1-interacting protein, further identified as Acetyl Coenzyme A (CoA) Carboxylase alpha (ACCA) [20].
• Using solution nuclear magnetic resonance (NMR) spectroscopy and mutational analysis, we have characterized the interaction of BRCA1-BRCT domains with a phosphoserine-containing peptide derived from the DNA repair helicase BACH1 [21].
• Cadmium induces nuclear export of Bach1, a transcriptional repressor of heme oxygenase-1 gene [22].
• The iron(II)-catalyzed Bach reaction of tert-butoxycarbonyl azide (BocN(3)) and allyl sulfides has been extended to include propargyl sulfides, which give N-allenylsulfenimide products [23].

Physical interactions of BRIP1

• FANCJ directly interacts with MLH1 independent of BRCA1, through its helicase domain [24].

Enzymatic interactions of BRIP1

• Here we report the crystal structure of the BRCT repeats of human BRCA1 bound to a phosphorylated BACH1 peptide at 2.3 A resolution [19].

Regulatory relationships of BRIP1

• Consistent with this, we show that FANCJ can inhibit RAD51 strand exchange, an activity that is likely to be important for its role in controlling DNA repair through homologous recombination [25].

Co-localisations of BRIP1

• Dependent on the presence of BRCA1, FANCJ colocalizes with RPA in nuclear foci after DNA damage [26].

Other interactions of BRIP1

• The BRIP1 helicase functions independently of BRCA1 in the Fanconi anemia pathway for DNA crosslink repair [2].
• These genes encode components of the FA "core" complex, a key factor FancD2, the familial breast cancer suppressor BRCA2/FancD1, and Brip1/FancJ helicase [27].
• BARD1, another BRCA1-interacting protein, was also found to interact with hMSH2 [28].
• Using the yeast two-hybrid system, we identified the four and a half LIM-only protein 2 (FHL2) as a novel BRCA1 interacting protein [29].
• Cofactor of BRCA1 (COBRA1), a novel protein, was isolated as a BRCA1-interacting protein [30].

Analytical, diagnostic and therapeutic context of BRIP1

• On the basis of published data and sequence analysis we suggest that SUVi/BACH1 may represent a novel subfamily of mammalian helicases, functioning in the processing of lesions induced by different genotoxic agents [31].
• Northern blot analysis revealed that BACH1 was expressed in all tissues examined [32].
• However, Bach1 did not bind to the MARE-like element in electrophoretic mobility shift assays (EMSA) [33].
• Results recently obtained in animal models, discussed here by Jean François Bach particularly with anti-CD3 and anti-CD4 monoclonal antibodies, indicate that reestablishment of tolerance to self antigens is a feasible goal [34].
• Hemispheric dominance in the processing of J.S. Bach fugues: a transcranial Doppler sonography (TCD) study with musicians [35].

References