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Volumn 8, Issue 1, 1998, Pages 14-20

Functions of the BRCA1 end BRCA2 genes

Author keywords

[No Author keywords available]

Indexed keywords

BRCA1 PROTEIN; BRCA2 PROTEIN; DNA; TRANSCRIPTION FACTOR; TUMOR PROTEIN;

EID: 0031594639     PISSN: 0959437X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0959-437X(98)80056-7     Document Type: Article
Times cited : (92)

References (62)
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    • The BRC repeats are conserved in mammalian BRCA2 proteins
    • of special interest. In [12], eight copies of a 30-80 amino acid repeat are noted in part of the BRCA2 protein encoded by exon 11. In this paper, comparison of the sequences of BRCA2 exon 11 from six mammalian species demonstrates that this region of the gene is poorly conserved overall. The BRC repeats, however, are among a few highly conserved regions.
    • Bignell G, Micklem G, Stratton MR, Ashworth A, Wooster R. The BRC repeats are conserved in mammalian BRCA2 proteins. of special interest Hum Mol Genet. 6:1997;53-58 In [12], eight copies of a 30-80 amino acid repeat are noted in part of the BRCA2 protein encoded by exon 11. In this paper, comparison of the sequences of BRCA2 exon 11 from six mammalian species demonstrates that this region of the gene is poorly conserved overall. The BRC repeats, however, are among a few highly conserved regions.
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    • Variation of risks of breast and ovarian cancer associated with different mutations of the BRCA2 gene
    • of special interest. This paper describes a genotype/phenotype correlation for a region of the BRCA2 gene, the OCCR, in which mutations predispose to ovarian rather than breast cancer. The mechanism for this remains obscure.
    • Gayther SA, Mangion J, Russell P, Seal S, Barfoot R, Ponder BAJ, Stratton MR, Easton D. Variation of risks of breast and ovarian cancer associated with different mutations of the BRCA2 gene. of special interest Nat Genet. 15:1997;103-105 This paper describes a genotype/phenotype correlation for a region of the BRCA2 gene, the OCCR, in which mutations predispose to ovarian rather than breast cancer. The mechanism for this remains obscure.
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    • Gayther, S.A.1    Mangion, J.2    Russell, P.3    Seal, S.4    Barfoot, R.5    Ponder, B.A.J.6    Stratton, M.R.7    Easton, D.8
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    • A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes
    • of special interest. A nice genetic study in which the 999del5 BRCA2 mutant is shown to be associated with male breast cancer in some families but not in others, providing evidence for modifying genes for penetrance of this BRCA2 mutation.
    • Thorlacius S, Olafsdottir G, Tryggvadottir L, Neuhausen S, Jonasson JG, Tavtigian SV, Tulinius H, Ogmundsdottir HM, Eyljord JE. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. of special interest Nat Genet. 13:1996;117-119 A nice genetic study in which the 999del5 BRCA2 mutant is shown to be associated with male breast cancer in some families but not in others, providing evidence for modifying genes for penetrance of this BRCA2 mutation.
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    • Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus
    • of special interest. Carriers of BRCA1 mutations harbouring one or two rare alleles at a VNTR linked to the Harvey - Ras proto-oncogene are at a modest (2.1 times) greater risk of ovarian but not breast cancer compared to carriers with common alleles. It is not clear whether this has anything to do with the Ras gene per se or is a marker of genomic instability.
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    • of special interest. A description of the amino acid sequence of mouse Brca2. Brca1 and Brca2 also appear to be evolving at similar rates and have overlapping patterns of expression within the adult mouse.
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    • Breast Cancer Linkage ConsortiumPathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. of outstanding interest. Comparison of tumours from carriers of BRCA1 and BRCA2 mutations with sporadic cases. Clear pathological differences are observed between the three groups, implying that the mechanism of tumourigenesis may be distinct in the three different types of tumour and different treatment regimens may be required.
    • Breast Cancer Linkage Consortium Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. of outstanding interest Lancet. 349:1997;1505-1510 Comparison of tumours from carriers of BRCA1 and BRCA2 mutations with sporadic cases. Clear pathological differences are observed between the three groups, implying that the mechanism of tumourigenesis may be distinct in the three different types of tumour and different treatment regimens may be required.
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    • Location of BRCA1 in human breast and ovarian cancer cells
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    • The nuclear localisation sequences of the BRCA1 protein interact with the importin-α subunit of the nuclear transport receptor
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    • Differential subcellular localisation, expression and biological toxicity of BRCA1 and the splice variant BRCA1-Δ11b
    • of special interest. A detailed and carefully performed study indicating that BRCA1 is very difficult to overexpress in cells and may be toxic. This finding suggests that caution should be exercised when interpreting the results of experiments where BRCA1 is expressed ectopically.
    • Wilson CA, Payton MN, Elliot GS, Buaas FW, Cajulis EE, Grosshans D, Ramos L, Reese DM, Slamon DJ, Calzone FJ. Differential subcellular localisation, expression and biological toxicity of BRCA1 and the splice variant BRCA1-Δ11b. of special interest Oncogene. 14:1997;1-16 A detailed and carefully performed study indicating that BRCA1 is very difficult to overexpress in cells and may be toxic. This finding suggests that caution should be exercised when interpreting the results of experiments where BRCA1 is expressed ectopically.
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    • Wilson, C.A.1    Payton, M.N.2    Elliot, G.S.3    Buaas, F.W.4    Cajulis, E.E.5    Grosshans, D.6    Ramos, L.7    Reese, D.M.8    Slamon, D.J.9    Calzone, F.J.10
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    • BRCA1 protein products: Reply
    • of outstanding interest. of special interest. These papers [34-36] add another dimension to the BRCA1 controversy. Jensen et al. [34] suggested that BRCA1 is a secreted protein. Subsequently, Wilson et al. [35] demonstrated that a key antibody used by Jensen et al. to reach this conclusion cross-reacts with some type I receptor tyrosine kinases which are frequently overexpressed in breast cancer cells. Given this, and the weight of evidence in favour of a nuclear location for BRCA1 [26,27,29,30,31,32,33,49,51,53,54], the reply of Jensen et al. [36] is unconvincing.
    • of outstanding interest Jensen RA, Thompson MA, Jetton TL, Van der Meer R, Helou B, Arteaga CL, Page DL, Holt JT, Tronick SR, Gown AM, et al. BRCA1 protein products: reply. of special interest Nat Genet. 13:1996;269-272 These papers [34-36] add another dimension to the BRCA1 controversy. Jensen et al. [34] suggested that BRCA1 is a secreted protein. Subsequently, Wilson et al. [35] demonstrated that a key antibody used by Jensen et al. to reach this conclusion cross-reacts with some type I receptor tyrosine kinases which are frequently overexpressed in breast cancer cells. Given this, and the weight of evidence in favour of a nuclear location for BRCA1 [26,27,29,30,31,32,33,49,51,53,54], the reply of Jensen et al. [36] is unconvincing.
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    • BRCA1 is localised in cytoplasmic tube-like invaginations in the nucleus
    • of special interest. More fuel on the fire of the BRCA1 controversy (see also [29,30,31,32,33-36]. This paper reports the presence of BRCA1-containing tubes within the nucleus which appear to originate from the perinuclear region and contain the endoplasmic reticulum proteins 58K, β-COP and protein disulphide isomerase.
    • Coene E, Van Oostveldt, Willems K, van Emmelo J, De Potter CR. BRCA1 is localised in cytoplasmic tube-like invaginations in the nucleus. of special interest Nat Genet. 16:1997;122-124 More fuel on the fire of the BRCA1 controversy (see also [29,30,31,32,33-36]. This paper reports the presence of BRCA1-containing tubes within the nucleus which appear to originate from the perinuclear region and contain the endoplasmic reticulum proteins 58K, β-COP and protein disulphide isomerase.
    • (1997) Nat Genet , vol.16 , pp. 122-124
    • Coene, E.1    Van Oostveldt2    Willems, K.3    Van Emmelo, J.4    De Potter, C.R.5
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    • of special interest. of outstanding interest. See annotation [40].
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    • The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse
    • of special interest. of outstanding interest. See annotation [40].
    • of special interest Hakem R, de la Pompa JL, Sirard C, Mo R, Woo M, Hakem A, Wakeham A, Potter J, Reitmair A, Billia F, et al. The tumor suppressor gene Brca1 is required for embryonic cellular proliferation in the mouse. of outstanding interest Cell. 85:1996;1009-1023 See annotation [40].
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    • Inactivation of the mouse Brca1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development
    • -/- embryos described in Gowen et al. [38] survive several days later than those in [39,40,43].
    • -/- embryos described in Gowen et al. [38] survive several days later than those in [39,40,43].
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    • Transcriptional activation by Brca1
    • of special interest. See annotation [48].
    • Chapman MS, Verma IM. Transcriptional activation by Brca1. of special interest Nature. 382:1996;678-679 See annotation [48].
    • (1996) Nature , vol.382 , pp. 678-679
    • Chapman, M.S.1    Verma, I.M.2
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    • Transcriptional activation functions in BRCA2
    • of special interest. This paper and [47] report regions of BRCA1 and BRCA2 proteins which, when fused to GAL4, can act as transcriptional activators in yeast and mammalian cells. This property, however, has not yet been reported for the full-length proteins. In [48] the transcriptional activation domain is shown to contain weak sequence similarity to c-Jun and it is suggested that Jun-kinase (JNK)-like kinases might regulate BRCA2 activity.
    • Milner J, Ponder B, Hughes-Davies L, Seltmann M, Kouzarides T. Transcriptional activation functions in BRCA2. of special interest Nature. 386:1997;772-773 This paper and [47] report regions of BRCA1 and BRCA2 proteins which, when fused to GAL4, can act as transcriptional activators in yeast and mammalian cells. This property, however, has not yet been reported for the full-length proteins. In [48] the transcriptional activation domain is shown to contain weak sequence similarity to c-Jun and it is suggested that Jun-kinase (JNK)-like kinases might regulate BRCA2 activity.
    • (1997) Nature , vol.386 , pp. 772-773
    • Milner, J.1    Ponder, B.2    Hughes-Davies, L.3    Seltmann, M.4    Kouzarides, T.5
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    • BRCA1 is a component of the RNA polymerase II holoenzyme
    • of special interest. BRCA1 was found to co-purify with the RNA polymerase II holoenzyme over multiple chromatographic steps whereas a mutant lacking the carboxy-terminal 11 amino acids did not associate with this complex. Rad51 has also been reported to be part of this complex by others (see [50]) but appears not to be present in the preparation reported here.
    • Scully R, Anderson SF, Chao DM, Wei W, Ye L, Young RA, Livingston DM, Parvin JD. BRCA1 is a component of the RNA polymerase II holoenzyme. of special interest Proc Natl Acad Sci USA. 94:1997;5605-5610 BRCA1 was found to co-purify with the RNA polymerase II holoenzyme over multiple chromatographic steps whereas a mutant lacking the carboxy-terminal 11 amino acids did not associate with this complex. Rad51 has also been reported to be part of this complex by others (see [50]) but appears not to be present in the preparation reported here.
    • (1997) Proc Natl Acad Sci USA , vol.94 , pp. 5605-5610
    • Scully, R.1    Anderson, S.F.2    Chao, D.M.3    Wei, W.4    Ye, L.5    Young, R.A.6    Livingston, D.M.7    Parvin, J.D.8
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    • Association of BRCA1 with Rad51 in mitotic and meiotic cells
    • of outstanding interest. This splendid paper demonstrates co-localisation of BRCA1 and Rad51 in discrete nuclear foci during S phase in mitotic cells. Moreover, the two proteins are shown to associate by co-immunoprecipitation. This association suggests a role for BRCA1 in DNA repair. In human meiotic cells, the BRCA1 and Rad51 proteins are associated with unsynapsed elements of the synaptonemal complex suggesting a role in recombination.
    • Scully R, Chen J, Plug A, Xiao Y, Weaver D, Feunteun J, Ashley T, Livingston DM. Association of BRCA1 with Rad51 in mitotic and meiotic cells. of outstanding interest Cell. 88:1997;265-275 This splendid paper demonstrates co-localisation of BRCA1 and Rad51 in discrete nuclear foci during S phase in mitotic cells. Moreover, the two proteins are shown to associate by co-immunoprecipitation. This association suggests a role for BRCA1 in DNA repair. In human meiotic cells, the BRCA1 and Rad51 proteins are associated with unsynapsed elements of the synaptonemal complex suggesting a role in recombination.
    • (1997) Cell , vol.88 , pp. 265-275
    • Scully, R.1    Chen, J.2    Plug, A.3    Xiao, Y.4    Weaver, D.5    Feunteun, J.6    Ashley, T.7    Livingston, D.M.8
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    • DNA repair: RAD alert
    • Ivanov EL, Haber JE. DNA repair: RAD alert. Curr Biol. 7:1997;492-495.
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    • Dynamic changes of BRCA1 subnuclear localisation and phosphorylation state are initiated by DNA damage
    • + replication structures which implies an interaction with damaged replicating DNA. Phosphorylation of BRCA1 in response to DNA damage (also described in [54]) by an unknown kinase that appears to be neither ATM nor DNA-PK is also described.
    • + replication structures which implies an interaction with damaged replicating DNA. Phosphorylation of BRCA1 in response to DNA damage (also described in [54]) by an unknown kinase that appears to be neither ATM nor DNA-PK is also described.
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    • of outstanding interest. In sporadic breast cancer, the frequency of p53 mutation is ≈20-40%. The authors of this paper make the very important observation of high frequency mutation of p53 in tumours from carriers of BRCA1 mutations.
    • Crook T, Crossland S, Crompton MR, Osin P, Gusterson BA. p53 mutations in BRCA1-sdassociated familial breast cancer. of outstanding interest Lancet. 350:1997;638-639 In sporadic breast cancer, the frequency of p53 mutation is ≈20-40%. The authors of this paper make the very important observation of high frequency mutation of p53 in tumours from carriers of BRCA1 mutations.
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    • Mazoyer S, Dunning AM, Serova O, Dearden J, Puget N, Healey CS, Gayther SA, Mangion J, Stratton MR, Lynch HT, et al. A polymorphic stop codon in BRCA2. of special interest Nat Genet. 14:1996;253-254 A polymorphic variant in exon 27 of the BRCA2 gene results in the introduction of a stop codon and loss of the last 93 amino acids of the protein, including a putative 'granin' motif [34]. This appears to have no obvious phenotypic consequences.
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    • Nuclear location and cell cycle regulation of the BRCA2 protein
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    • Bertwistle, D.1    Swift, S.2    Marston, N.J.3    Jackson, L.E.4    Crossland, S.5    Crompton, M.R.6    Marshall, C.J.7    Ashworth, A.8
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    • Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation
    • of outstanding interest. Previously reported mutations of the Brca2 gene [41-43], were lethal early in embryogenesis when homozygous. This paper reports the generation of viable Brca2 mutant mice which survive to develop thymic lymphomas. In addition, a role for Brca2 in DNA repair is directly demonstrated in fibroblasts from Brca2 mutant embryos.
    • Connor F, Bertwistle D, Mee PJ, Ross GM, Swift S, Grigorieva E, Tybulewicz VLJ, Ashworth A. Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation. of outstanding interest Nat Genet. 17:1997;423-430 Previously reported mutations of the Brca2 gene [41-43], were lethal early in embryogenesis when homozygous. This paper reports the generation of viable Brca2 mutant mice which survive to develop thymic lymphomas. In addition, a role for Brca2 in DNA repair is directly demonstrated in fibroblasts from Brca2 mutant embryos.
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    • Connor, F.1    Bertwistle, D.2    Mee, P.J.3    Ross, G.M.4    Swift, S.5    Grigorieva, E.6    Tybulewicz, V.L.J.7    Ashworth, A.8
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    • RAD51 interacts with the evolutionary conserved BRC motifs in the human breast cancer susceptibility gene brca2
    • of special interest. Using the yeast two-hybrid and biochemical assays, the authors demonstrate that the eight BRC repeats present in the BRCA2 protein interact specifically with the Rad51 protein.
    • Wong AKC, Pero R, Ormonde PA, Tavtigan SV, Bartel PL. RAD51 interacts with the evolutionary conserved BRC motifs in the human breast cancer susceptibility gene brca2. of special interest J Biol Chem. 272:1997;31941-31944 Using the yeast two-hybrid and biochemical assays, the authors demonstrate that the eight BRC repeats present in the BRCA2 protein interact specifically with the Rad51 protein.
    • (1997) J Biol Chem , vol.272 , pp. 31941-31944
    • Wong, A.K.C.1    Pero, R.2    Ormonde, P.A.3    Tavtigan, S.V.4    Bartel, P.L.5


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.