Functions of the BRCA1 and BRCA2 genes.

Mutations in the BRCA1 and BRCA2 genes confer a high risk of breast cancer development. Both genes encode very large proteins of unknown function but recent results suggest that they may have roles in transcriptional regulation and DNA repair. These advances offer the prospect of understanding not only the normal cellular function of these genes but also how their loss leads to tumour formation.

[1]  M. Stratton Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases , 1997, The Lancet.

[2]  P. Polakis,et al.  Induction of phosphorylation on BRCA1 during the cell cycle and after DNA damage. , 1997, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[3]  A. Ashworth,et al.  Nuclear location and cell cycle regulation of the BRCA2 protein. , 1997, Cancer research.

[4]  Ralph Scully,et al.  Dynamic Changes of BRCA1 Subnuclear Location and Phosphorylation State Are Initiated by DNA Damage , 1997, Cell.

[5]  C. Osborne,et al.  Aberrant Subcellular Localization of BRCA1 in Breast Cancer , 1995, Science.

[6]  M. Justice,et al.  Identification of the murine beige gene by YAC complementation and positional cloning , 1996, Nature Genetics.

[7]  Anne M. Bowcock,et al.  Identification of a RING protein that can interact in vivo with the BRCA1 gene product , 1996, Nature Genetics.

[8]  Danny Reinberg,et al.  A human RNA polymerase II complex associated with SRB and DNA-repair proteins , 1996, Nature.

[9]  R. Young,et al.  BRCA1 is a component of the RNA polymerase II holoenzyme. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[10]  A. Ashworth,et al.  Tumorigenesis and a DNA repair defect in mice with a truncating Brca2 mutation , 1997, Nature Genetics.

[11]  J. Rossant,et al.  The Tumor Suppressor Gene Brca1 Is Required for Embryonic Cellular Proliferation in the Mouse , 1996, Cell.

[12]  D. Slamon,et al.  Differential subcellular localization, expression and biological toxicity of BRCA1 and the splice variant BRCA1-Δ11b , 1997, Oncogene.

[13]  Y. Chen,et al.  BRCA1 is a 220-kDa nuclear phosphoprotein that is expressed and phosphorylated in a cell cycle-dependent manner. , 1996, Cancer research.

[14]  L. Chodosh,et al.  Brca2 is coordinately regulated with Brca1 during proliferation and differentiation in mammary epithelial cells. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[15]  A. Berchuck,et al.  Cell cycle control of BRCA2. , 1996, Cancer research.

[16]  Bert Vogelstein,et al.  Gatekeepers and caretakers , 1997, Nature.

[17]  Eugene V. Koonin,et al.  …Functional motifs… , 1996, Nature Genetics.

[18]  Yumay Chen,et al.  The Nuclear Localization Sequences of the BRCA1 Protein Interact with the Importin-α Subunit of the Nuclear Transport Signal Receptor* , 1996, The Journal of Biological Chemistry.

[19]  J. Haber,et al.  DNA repair: RAD alert , 1997, Current Biology.

[20]  I. Verma,et al.  Transcriptional activation by BRCA1 , 1996, Nature.

[21]  M. King,et al.  Reply to “…and secreted tumour suppressors” , 1996, Nature Genetics.

[22]  M. Stratton,et al.  A polymorphic stop codon in BRCA2 , 1996, Nature Genetics.

[23]  A. Futreal,et al.  BRCA1 expression is not directly responsive to estrogen , 1997, Oncogene.

[24]  P. Bork,et al.  Internal repeats in the BRCA2 protein sequence , 1996, Nature Genetics.

[25]  T. Ludwig,et al.  Targeted mutations of breast cancer susceptibility gene homologs in mice: lethal phenotypes of Brca1, Brca2, Brca1/Brca2, Brca1/p53, and Brca2/p53 nullizygous embryos. , 1997, Genes & development.

[26]  M. Stratton,et al.  Hereditary predisposition to breast cancer. , 1996, Current opinion in genetics & development.

[27]  P. Leder,et al.  Expression of Brca1 is associated with terminal differentiation of ectodermally and mesodermally derived tissues in mice. , 1995, Genes & development.

[28]  C. Osborne,et al.  Response: Location of BRCA1 in Human Breast and Ovarian Cancer Cells , 1996, Science.

[29]  D. Clayton,et al.  Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype–phenotype correlation , 1995, Nature Genetics.

[30]  H. Ruffner,et al.  BRCA1 is a cell cycle-regulated nuclear phosphoprotein. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[31]  T. Mak,et al.  Partial rescue of Brca15–6 early embryonic lethality by p53 or p21 null mutation , 1997, Nature Genetics.

[32]  T. Jacks Tumor suppressor gene mutations in mice. , 1999, Annual review of genetics.

[33]  M. King,et al.  Inherited breast and ovarian cancer. , 1995, Human molecular genetics.

[34]  G. Eichele,et al.  Embryonic lethality and radiation hypersensitivity mediated by Rad51 in mice lacking Brca2 , 1997, Nature.

[35]  B. Koller,et al.  Brca1 deficiency results in early embryonic lethality characterized by neuroepithelial abnormalities , 1996, Nature Genetics.

[36]  S. Thukral,et al.  BRCA1 protein products: Antibody specificity… , 1996, Nature Genetics.

[37]  Junzhe Xu,et al.  The developmental pattern of Brca1 expression implies a role in differentiation of the breast and other tissues , 1995, Nature Genetics.

[38]  A. Bowcock,et al.  BRCA1 and BRCA2 mRNA levels are coordinately elevated in human breast cancer cells in response to estrogen. , 1996, Oncogene.

[39]  T. Mak,et al.  Brca2 is required for embryonic cellular proliferation in the mouse. , 1997, Genes & development.

[40]  P. Freemont,et al.  Does this have a familiar RING? , 1996, Trends in biochemical sciences.

[41]  M. Stratton,et al.  Ovarian cancer risk in BRCA1 carriers is modified by the HRAS1 variable number of tandem repeat (VNTR) locus , 1996, Nature Genetics.

[42]  R. McFarlane,et al.  A human BRCA1 gene knockout , 1995, Nature.

[43]  D. Bentley,et al.  Identification of the breast cancer susceptibility gene BRCA2 , 1995, Nature.

[44]  Yonghong Xiao,et al.  Association of BRCA1 with Rad51 in Mitotic and Meiotic Cells , 1997, Cell.

[45]  J. Mornon,et al.  From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair , 1997, FEBS letters.

[46]  Luke Hughes-Davies,et al.  Transcriptional activation functions in BRCA2 , 1997, Nature.

[47]  S. Seal,et al.  Brave new now , 2013, Nature Genetics.

[48]  M. Stratton,et al.  Recent advances in understanding of genetic susceptibility to breast cancer. , 1996, Human molecular genetics.

[49]  B. Gusterson,et al.  p53 mutations in BRCA1-associated familial breast cancer , 1997, The Lancet.

[50]  D. Easton Breast cancer genes—what are the real risks? , 1997, Nature Genetics.

[51]  M. King,et al.  BRCA1 is secreted and exhibits properties of a granin , 1996, Nature Genetics.

[52]  Steven E. Bayer,et al.  A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. , 1994, Science.

[53]  C. Osborne,et al.  Location of BRCA1 in Human Breast and Ovarian Cancer Cells , 1996, Science.

[54]  T. Jacks,et al.  Double indemnity: p53, BRCA and cancer , 1997, Nature Medicine.

[55]  A. Ashworth,et al.  Cloning, chromosomal mapping and expression pattern of the mouse Brca2 gene. , 1997, Human molecular genetics.

[56]  A. Ashworth,et al.  The BRC repeats are conserved in mammalian BRCA2 proteins. , 1997, Human molecular genetics.

[57]  J. Eyfjörd,et al.  A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes , 1996, Nature Genetics.

[58]  J. Rommens,et al.  The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds , 1996, Nature Genetics.

[59]  P. Oostveldt,et al.  BRCA1 is localized in cytoplasmic tube-like invaginations in the nucleus , 1997, Nature Genetics.

[60]  G. Woude,et al.  Abnormal Centrosome Amplification in the Absence of p53 , 1996, Science.

[61]  P. Bartel,et al.  RAD51 Interacts with the Evolutionarily Conserved BRC Motifs in the Human Breast Cancer Susceptibility Gene brca2 * , 1997, The Journal of Biological Chemistry.

[62]  C. Liu,et al.  Inactivation of the mouse Brca1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development. , 1996, Genes & development.