BRCA1 Protein: The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)Genes, BRCA1: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.BRCA2 Protein: A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)Genes, BRCA2: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.Breast Neoplasms: Tumors or cancer of the human BREAST.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Founder Effect: A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.Breast Neoplasms, Male: Any neoplasms of the male breast. These occur infrequently in males in developed countries, the incidence being about 1% of that in females.Neoplastic Syndromes, Hereditary: The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Genetic Counseling: An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.Salpingectomy: Excision of one or both of the FALLOPIAN TUBES.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Homologous Recombination: An exchange of DNA between matching or similar sequences.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Ubiquitin-Protein Ligases: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.Fallopian Tube Neoplasms: Benign or malignant neoplasms of the FALLOPIAN TUBES. They are uncommon. If they develop, they may be located in the wall or within the lumen as a growth attached to the wall by a stalk.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Heterozygote Detection: Identification of genetic carriers for a given trait.PhthalazinesFamily Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Cell Line, Tumor: A cell line derived from cultured tumor cells.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Xenopsylla: A genus of fleas in the family Pulicidae which includes the species that serves as the primary vector of BUBONIC PLAGUE, Xenopsylla cheopis.Rodenticides: Substances used to destroy or inhibit the action of rats, mice, or other rodents.Rodent Control: The reduction or regulation of the population of noxious, destructive, or dangerous rodents through chemical, biological, or other means.VirginiaWallerian Degeneration: Degeneration of distal aspects of a nerve axon following injury to the cell body or proximal portion of the axon. The process is characterized by fragmentation of the axon and its MYELIN SHEATH.raf Kinases: A family of closely-related serine-threonine kinases that were originally identified as the cellular homologs of the retrovirus-derived V-RAF KINASES. They are MAP kinase kinase kinases that play important roles in SIGNAL TRANSDUCTION.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.Ubiquitin: A highly conserved 76-amino acid peptide universally found in eukaryotic cells that functions as a marker for intracellular PROTEIN TRANSPORT and degradation. Ubiquitin becomes activated through a series of complicated steps and forms an isopeptide bond to lysine residues of specific proteins within the cell. These "ubiquitinated" proteins can be recognized and degraded by proteosomes or be transported to specific compartments within the cell.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Yucca: A genus (and common name) in the AGAVACEAE family. It is known for SAPONINS in the root that are used in SOAPS.Atlases as Topic: Collections of illustrative plates, charts, etc., usually with explanatory captions.Prostate: A gland in males that surrounds the neck of the URINARY BLADDER and the URETHRA. It secretes a substance that liquefies coagulated semen. It is situated in the pelvic cavity behind the lower part of the PUBIC SYMPHYSIS, above the deep layer of the triangular ligament, and rests upon the RECTUM.Proteomics: The systematic study of the complete complement of proteins (PROTEOME) of organisms.Cellular Apoptosis Susceptibility Protein: A nucleocytoplasmic transport protein that binds to ALPHA KARYOPHERINS and RAN GTP BINDING PROTEIN inside the CELL NUCLEUS and participates in their export into CYTOPLASM. It is also associated with the regulation of APOPTOSIS and microtubule assembly.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.

Mapping the functional domains of BRCA1. Interaction of the ring finger domains of BRCA1 and BARD1. (1/1487)

Breast cancer 1 (BRCA1) and BRCA1-associated RING domain 1 (BARD1) are multidomain proteins that interact in vivo via their N-terminal RING finger motif regions. To characterize functional aspects of the BRCA1/BARD1 interaction, we have defined the structural domains required for the interaction, as well as their oligomerization state, relative stability, and possible nucleic acid binding activity. We have found that the RING finger motifs do not themselves constitute stable structural domains but are instead part of larger domains comprising residues 1-109 of BRCA1 and residues 26-119 of BARD1. These domains exist as homodimers and preferentially form a stable heterodimer. Shorter BRCA1 RING finger constructs do not interact with BARD1 or with longer BRCA1 constructs, indicating that the heterodimeric and homodimer interactions are mediated by regions outside the canonical RING finger motif. Nucleic acid binding is a generally proposed function of RING finger domains. We show that neither the homodimers nor the heterodimer displays affinity for nucleic acids, indicating that the proposed roles of BRCA1 and BARD1 in DNA repair and/or transcriptional activation must be mediated either by other regions of the proteins or by additional cofactors.  (+info)

Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1. (2/1487)

An increasing number of transcription factors have been shown to activate DNA replication. However, the underlying mechanism remains to be elucidated. Here it is shown that when tethered to a cellular replication origin, the acidic transcriptional activation domain of the breast cancer protein BRCA1 alters the local chromatin structure and stimulates chromosomal DNA replication. Cancer-predisposing mutations in BRCA1 that abolish transcriptional activation also prevent chromatin remodeling and activation of replication. Chromatin remodeling occurs even in the absence of a functional replication origin. Thus, increasing chromatin accessibility may be an important mechanism used by transcription factors to facilitate multiple nuclear processes.  (+info)

Should insurance pay for preventive services suggested by genetics? (3/1487)

Physicians, plans and patients are discovering that the promise of genetic testing will be hard to fulfill. Even when a test can show predisposition toward a disease, performing it can't necessarily improve medical outcomes. Unfortunately, doing these tests can have some unintended negative effects.  (+info)

BRCA1 and BRCA2 proteins: roles in health and disease. (4/1487)

Between 5% and 10% of all breast cancer is hereditary, with patients having a strong family history of the disease. The remaining 90-95% of cases are classed as sporadic. Within the inherited group, 80-90% of cases are the result of germline mutations affecting two recently identified genes: BRCA1 and BRCA2. Since the sequencing of these genes, considerable research on the genetics of the mutation carriers has been performed, with less attention having been focused on the BRCA1 and BRCA2 proteins themselves. The structure and function of the protein products thus continues to hold mystery and might be the key to the full understanding of this complex disease.  (+info)

Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage. (5/1487)

Mutations in BRCA1 are responsible for nearly all of the hereditary ovarian and breast cancers, and about half of those in breast cancer-only kindreds. The ability of BRCA1 to transactivate the p21 promoter can be inactivated by mutation of the conserved BRCA1 C-terminal (BRCT) repeats. To explore the mechanisms of this BRCA1 function, the BRCT repeats were used as bait in a yeast two-hybrid screen. A known protein, CtIP, a co-repressor with CtBP, was found. CtIP interacts specifically with the BRCT repeats of BRCA1, both in vitro and in vivo, and tumor-derived mutations in this region abolished these interactions. The association of BRCA1 with CtIP was also abrogated in cells treated with DNA-damaging agents including UV, gamma-irradiation, and adriamycin, a response correlated with BRCA1 phosphorylation. The transactivation of the p21 promoter by BRCA1 was diminished by expression of exogenous CtIP and CtBP. These results suggest that the binding of the BRCT repeats of BRCA1 to CtIP/CtBP is critical in mediating transcriptional regulation of p21 in response to DNA damage.  (+info)

Germline BRCA1 alterations in a population-based series of ovarian cancer cases. (6/1487)

The objective of this study was to provide more accurate frequency estimates of breast cancer susceptibility gene 1 ( BRCA1 ) germline alterations in the ovarian cancer population. To achieve this, we determined the prevalence of BRCA1 alterations in a population-based series of consecutive ovarian cancer cases. This is the first population-based ovarian cancer study reporting BRCA1 alterations derived from a comprehensive screen of the entire coding region. One hundred and seven ovarian cancer cases were analyzed for BRCA1 alterations using the RNase mismatch cleavage assay followed by direct sequencing. Two truncating mutations, 962del4 and 3600del11, were identified. Both patients had a family history of breast or ovarian cancer. Several novel as well as previously reported uncharacterized variants were also identified, some of which were associated with a family history of cancer. The frequency distribution of common polymorphisms was determined in the 91 Caucasian cancer cases in this series and 24 sister controls using allele-specific amplification. The rare form of the Q356R polymorphism was significantly ( P = 0.03) associated with a family history of ovarian cancer, suggesting that this polymorphism may influence ovarian cancer risk. In summary, our data suggest a role for some uncharacterized variants and rare forms of polymorphisms in determining ovarian cancer risk, and highlight the necessity to screen for missense alterations as well as truncating mutations in this population.  (+info)

Centrosome amplification and a defective G2-M cell cycle checkpoint induce genetic instability in BRCA1 exon 11 isoform-deficient cells. (7/1487)

Germline mutations of the Brca1 tumor suppressor gene predispose women to breast and ovarian cancers. To study mechanisms underlying BRCA1-related tumorigenesis, we derived mouse embryonic fibroblast cells carrying a targeted deletion of exon 11 of the Brca1 gene. We show that the mutant cells maintain an intact G1-S cell cycle checkpoint and proliferate poorly. However, a defective G2-M checkpoint in these cells is accompanied by extensive chromosomal abnormalities. Mutant fibroblasts contain multiple, functional centrosomes, which lead to unequal chromosome segregation, abnormal nuclear division, and aneuploidy. These data uncover an essential role of BRCA1 in maintaining genetic stability through the regulation of centrosome duplication and the G2-M checkpoint and provide a molecular basis for the role of BRCA1 in tumorigenesis.  (+info)

Methylation of the BRCA1 promoter region in sporadic breast and ovarian cancer: correlation with disease characteristics. (8/1487)

Reduced expression of BRCA1 has been reported in sporadic breast cancer, although the mechanisms underlying this phenomenon remain unclear. Abnormal methylation leading to silencing of tumour suppressor genes has been implicated in tumorigenesis in a wide range of sporadic cancers. Therefore, we sought to determine the frequency of methylation within the BRCA1 promoter region in a large group of sporadic invasive breast (n =96) and ovarian (n = 43) carcinomas using Southern analyses. Overall, methylation was detected in 11% of breast cancer cases and in 5% of ovarian tumours. Methylation of the BRCA1 promoter region was strongly correlated with lack of estrogen and progesterone receptor expression. It is clear from the frequency of abnormal methylation of the BRCA1 promoter region, that this cannot be the sole mechanism mediating the reduced expression of BRCA1 that has previously been reported to occur in the majority of invasive sporadic breast tumours. Nevertheless this study suggests that abnormal methylation of the BRCA1 promoter may be important in tumorigenesis in a subset of sporadic breast and ovarian cancers.  (+info)

*BRCA1

The human BRCA1 protein consists of four major protein domains; the Znf C3HC4- RING domain, the BRCA1 serine domain and two ... BRCA1 and BRCA1 (/ˌbrækəˈwʌn/) are a human gene and its protein product, respectively. The official symbol (BRCA1, italic for ... The BRCA1 RING motif is flanked by alpha helices formed by residues 8-22 and 81-96 of the BRCA1 protein. It interacts with a ... A protein called valosin-containing protein (VCP, also known as p97) plays a role to recruit BRCA1 to the damaged DNA sites. ...

*USF2

"Novel consensus DNA-binding sequence for BRCA1 protein complexes". Molecular Carcinogenesis. 38 (2): 85-96. doi:10.1002/mc. ... "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi: ... USF2 has been shown to interact with USF1 (human gene), PPRC1 and BRCA1. The USF2 gene is repressed by the microRNA miR-10a. ... Upstream stimulatory factor 2 is a protein that in humans just encoded by the USF2 gene. This gene encodes a member of the ...

*UIMC1

BRCA1-A complex subunit RAP80 is a protein that in humans is encoded by the UIMC1 gene. GRCh38: Ensembl release 89: ... 2007). "Abraxas and RAP80 form a BRCA1 protein complex required for the DNA damage response". Science. 316 (5828): 1194-8. doi: ... Kim H, Chen J, Yu X (2007). "Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response". Science. 316 (5828 ... 2007). "The ubiquitin-interacting motif containing protein RAP80 interacts with BRCA1 and functions in DNA damage repair ...

*RNA Helicase A

Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD (Jul 1998). "BRCA1 protein is linked to the RNA polymerase II ... Anderson SF, Schlegel BP, Nakajima T, Wolpin ES, Parvin JD (Jul 1998). "BRCA1 protein is linked to the RNA polymerase II ... "Overexpression of a protein fragment of RNA helicase A causes inhibition of endogenous BRCA1 function and defects in ploidy and ... Westberg C, Yang JP, Tang H, Reddy TR, Wong-Staal F (Jul 2000). "A novel shuttle protein binds to RNA helicase A and activates ...

*Premature ovarian failure

In addition to BRCA1, the MCM8-MCM9 protein complex also plays a crucial role in the recombinational repair of DNA double- ... BRCA1 protein plays an essential role in the repair of DNA double-strand breaks by homologous recombination. Women with a ... BRCA1 mutations are associated with occult primary ovarian insufficiency. Impairment of the repair of DNA double-strand breaks ... Oktay K, Kim JY, Barad D, Babayev SN (2010). "Association of BRCA1 mutations with occult primary ovarian insufficiency: a ...

*Cancer

"Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast ... An average cancer of the breast or colon can have about 60 to 70 protein-altering mutations, of which about three or four may ... Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast ... As an example, one study listed protein coding genes that were frequently altered in their methylation in association with ...

*MicroRNA

A 2003 study showed that HMGA1 protein binds to the promoter region of DNA repair gene BRCA1 and inhibits BRCA1 promoter ... April 2003). "Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in ... binding protein], PACT (protein activator of the interferon-induced protein kinase), the SMN complex, fragile X mental ... HMGA2 protein specifically targets the promoter of ERCC1, thus reducing expression of this DNA repair gene. ERCC1 protein ...

*DNA repair

April 2003). "Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in ... The PARP1 protein, attached to both DDB1 and DDB2, then PARylates (creates a poly-ADP ribose chain) on DDB2 that attracts the ... PARP1 protein starts to appear at DNA damage sites in less than a second, with half maximum accumulation within 1.6 seconds ... BRCA1 and BRCA2, two famous genes whose mutations confer a hugely increased risk of breast cancer on carriers, are both ...

*Carcinogenesis

"Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast ... The protein-coding DNA within the nucleus is about 1.5% of the total genomic DNA. Within this protein-coding DNA (called the ... The p53 protein, one of the most important studied tumor suppressor genes, is a transcription factor activated by many cellular ... Finally, inherited mutations in BRCA1 and BRCA2 lead to early onset of breast cancer. Development of cancer was proposed in ...

*Cancer epigenetics

Baldassarre et al., showed that HMGA1 protein binds to the promoter region of DNA repair gene BRCA1 and inhibits BRCA1 promoter ... April 2003). "Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in ... RAP80, a subunit of the DNA repair breast cancer type 1 susceptibility protein complex (BRCA1-A), binds ubiquitin attached to ... HMGA2 protein specifically targets the promoter of ERCC1, thus reducing expression of this DNA repair gene. ERCC1 protein ...

*Colorectal cancer

"Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in sporadic breast ... The APC protein prevents the accumulation of β-catenin protein. Without APC, β-catenin accumulates to high levels and ... The p53 protein, produced by the TP53 gene, normally monitors cell division and kills cells if they have Wnt pathway defects. ... Sometimes TGF-β is not deactivated, but a downstream protein named SMAD is deactivated. DCC commonly has a deleted segment of a ...

*KPNA6

1997). "The nuclear localization sequences of the BRCA1 protein interact with the importin-alpha subunit of the nuclear ... Importin alpha enters the nucleoplasm with its passenger protein and importin beta remains at the pore. The protein encoded by ... 1994). "The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in ... Importin subunit alpha-7 is a protein that in humans is encoded by the KPNA6 gene. Nucleocytoplasmic transport, a signal- and ...

*Ubiquitin

The BRCA1 gene is another tumor suppressor gene in human which encodes the BRCA1 protein that is involved in response to DNA ... The protein contains a RING motif with E3 Ubiquitin Ligase activity. BRCA1 could form dimer with other molecules, such as BARD1 ... Kim H, Chen J, Yu X (May 2007). "Ubiquitin-binding protein RAP80 mediates BRCA1-dependent DNA damage response". Science. 316 ( ... The protein modifications can be either a single ubiquitin protein (monoubiquitination) or a chain of ubiquitin ( ...

*RBBP8

"The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. ... Retinoblastoma-binding protein 8 is a protein that in humans is encoded by the RBBP8 gene. The protein encoded by this gene is ... "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. ... This protein complexes with transcriptional co-repressor CTBP. It is also associated with BRCA1 and is thought to modulate the ...

*DNA methylation in cancer

MiR-182 targets the BRCA1 messenger RNA and may be a major cause of reduced BRCA1 protein expression in many breast cancers ( ... In cancer, a number of mutational changes are found in protein coding genes. Colorectal cancers typically have 3 to 6 driver ... Individual miRNAs can each target, and repress transcription of, on average, roughly 200 messenger RNAs of protein coding genes ... In mammals, microRNAs (miRNAs) regulate the transcriptional activity of about 60% of protein-encoding genes. ...

*BRIP1

Fanconi anemia group J protein is a protein that in humans is encoded by the BRCA1-interacting protein 1 (BRIP1) gene. The ... "Entrez Gene: BRIP1 BRCA1 interacting protein C-terminal helicase 1". Rafnar T, Gudbjartsson DF, Sulem P, Jonasdottir A, ... 2004). "The BRCA1-associated protein BACH1 is a DNA helicase targeted by clinically relevant inactivating mutations". Proc. ... 2004). "Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands ...

*Proximity ligation assay

Vincent A, Berthel E, Dacheux E, Magnard C, Venezia NL (April 2016). "BRCA1 affects protein phosphatase 6 signalling through ... Wang S, Yoo S, Kim HY, Wang M, Zheng C, Parkhouse W, Krieger C, Harden N (January 2015). "Detection of in situ protein-protein ... protein interactions and modifications with high specificity and sensitivity. Protein targets can be readily detected and ... A variation of the technique (rISH-PLA) has been used to study the association of protein and RNA. Gullberg M, Gústafsdóttir SM ...

*BAP1

"Defining biochemical functions for the BRCA1 tumor suppressor protein: analysis of the BRCA1 binding protein BAP1". Cancer ... Nishikawa H, Wu W, Koike A, Kojima R, Gomi H, Fukuda M, Ohta T (Jan 2009). "BRCA1-associated protein 1 interferes with BRCA1/ ... BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase) is a deubiquitinating enzyme that in humans is encoded by the ... "Entrez Gene: BAP1 BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)". Gaytán de Ayala Alonso A, Gutiérrez L, ...

*LMO4

2002). "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity ... "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity". J. ... 2003). "Mutational analysis of the LMO4 gene, encoding a BRCA1-interacting protein, in breast carcinomas". Int. J. Cancer. 107 ... 2007). "Stabilization of a binary protein complex by intein-mediated cyclization". Protein Sci. 15 (11): 2612-8. doi:10.1110/ps ...

*LDB1

2002). "The LIM domain protein LMO4 interacts with the cofactor CtIP and the tumor suppressor BRCA1 and inhibits BRCA1 activity ... LIM domain-binding protein 1 is a protein that in humans is encoded by the LDB1 gene. LDB1 has been shown to interact with LMO4 ... 1997). "LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1". Leukemia. 11 Suppl 3: 307-12 ... encoding a BRCA1-interacting protein, in breast carcinomas". Int. J. Cancer. United States. 107 (1): 155-8. doi:10.1002/ijc. ...

*FANCA

This mechanic is also supported by the protein-protein interactions between BRG1 and both BRCA1 and FANCA, that serve to ... Instead BRCA1 protein may be more crucial in the detection of double stranded DNA breaks, or an intermediate in interstrand ... Amongst known FANC proteins, most evidence points for a direct interaction primarily between FANCA protein and BRCA1. Evidence ... Gordon SM, Buchwald M (2003). "Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid ...

*TERF2

... and BRCA1 protein transposition, may cause a reduction in telomere length, further contributing to multistage carcinogenesis of ... There are 4 domain categories on the TERF2 protein that allow it to bind to both other proteins in the shelterin protein ... This domain contains a motif for binding the shelterin protein TIN2, which acts as a stabilizing protein, connecting units that ... This protein is present at telomeres in metaphase of the cell cycle, is a second negative regulator of telomere length, and ...

*Ovary

The BRCA1 protein plays a key role in a type of DNA repair termed homologous recombinational repair that is the only known ... also found that expression of 4 key genes necessary for homologous recombinational repair of DNA double-strand breaks (BRCA1, ... "Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans". Sci Transl Med. 5 (172 ... "Premature menopause in patients with BRCA1 gene mutation". Breast Cancer Res Treat. 100 (1): 59-63. doi:10.1007/s10549-006-9220 ...

*Association for Molecular Pathology v. Myriad Genetics, Inc.

... coding for a BRCA1 protein, with specific variations from the norm that are indicative of susceptibility to breast cancer and ... and McGill University published the sequence of BRCA1, which they had isolated. In that same year, the first BRCA1 U.S. patent ... The same issue, namely the patentability of the DNA sequence in the BRCA1 gene, was considered in a February 2013 case in the ... Judge Bryson aptly noted that, "[a]s the first party with knowledge of the [BRCA1 and BRCA2] sequences, Myriad was in an ...

*FHL2

The FHL2 protein interacts with the breast cancer type 1 susceptibility gene (BRCA1) which enhances the transactivation of ... The Four-and-a-half LIM (FHL)-only protein subfamily is one of the members of the LIM-only protein family. Protein members ... "Protein-protein interaction of FHL2, a LIM domain protein preferentially expressed in human heart, with hCDC47". Journal of ... "Protein-protein interaction of FHL2, a LIM domain protein preferentially expressed in human heart, with hCDC47". J. Cell. ...

*ABL (gene)

Welch PJ, Wang JY (November 1993). "A C-terminal protein-binding domain in the retinoblastoma protein regulates nuclear c-Abl ... Abl gene has been shown to interact with: ABI1, ABI2, ABL2, ATM, BCAR1, BCR, BRCA1, CAT, CBL, CRKL, DOK1, EPHB2, GPX1, GRB10, ... Yamanashi Y, Baltimore D (January 1997). "Identification of the Abl- and rasGAP-associated 62 kDa protein as a docking protein ... "Cytoskeletal protein PSTPIP1 directs the PEST-type protein tyrosine phosphatase to the c-Abl kinase to mediate Abl ...
BRCA1 is a breast cancer susceptibility gene that is down-regulated in a significant proportion of sporadic breast cancers. BRCA1 is posttranscriptionally regulated by RNA-binding proteins, the identities of which are unknown. HuR is an RNA binding protein implicated in posttranscriptional regulation of many genes and is overexpressed in sporadic breast cancer. To investigate the possibility that these two molecules are functionally linked in breast cancer, we performed bioinformatic analysis of the BRCA1 3 untranslated region (UTR), RNA-protein assays with the HuR protein and the BRCA1 3UTR, and immunohistochemical analysis of a cohort of breast tumors using antibodies against BRCA1 and HuR. Here, we describe the identification of two predicted HuR-binding sites in the BRCA1 3UTR, one of which binds specifically to HuR. We also show that this interaction is disrupted by single nucleotide substitutions in the BRCA1 3UTR and that endogenous HuR protein associates with BRCA1 transcripts in ...
Given how BRCA2 is believed to function as a tumour suppressor, assays related to DNA repair are directly relevant to predicting the impact of BRCA2 variants on cancer risk and therapeutic response. Additionally, such assays have demonstrated high sensitivity and specificity for predicting known benign and pathogenic variants. For these reasons, DNA repair-related assays are considered here.21 Since DNA repair-related domains are distributed throughout BRCA2, as discussed earlier, such assays should be based on expression of full-length BRCA2. BRCA2 is even larger than BRCA1 (the protein is ~390 kDa and the cDNA is 10 254 bp). Thus, it has been difficult to express full-length BRCA2 in human cells using a cDNA.69 73 As such, some functional studies of BRCA2 VUS have been based on heterologous expression of full-length BRCA2 variants in mouse ESCs using BACs.71 72 These studies, in the laboratory of Shyam Sharan, focused on VUS in the N-terminal PALB2-binding domain and the C-terminal DBD, where ...
Breast Cancer is very common among Canadians. The Canadian Breast Cancer Foundation reported in 2014 " 1 in 9 women in Canada is expected to develop breast cancer during her lifetime." Today we are focusing on the genetic aspects of developing breast cancer in the body.. BRCA1 and BRCA2 genes - BRCA1 and BRCA 2 known, as a Breast Cancer Susceptibility Gene 1 and Breast Cancer Susceptibility Gene 2 are human genes and works as tumor suppressors.. How BRCA1 and BRCA2 connect to cancer? When any of those genes mutate, it causes DNA damage and it might not be able to repair properly, and as a results cell can develop additional genetic alterations. Inherited mutations in BRCA1 and BRCA2 then increase the risk of breast and ovarian cancer.. NOTE: BRCA1 and BRCA2 mutations can be inherited from a persons mother or father. Anyone who has inherited a BRCA1 or BRCA2 mutation could be an increase risk of developing breast and ovarian cancer.. Breast cancer statistics - Breast Cancer Society of Canada has ...
TY - JOUR. T1 - Inhibition of BRCT(BRCA1)-phosphoprotein interaction enhances the cytotoxic effect of olaparib in breast cancer cells. T2 - A proof of concept study for synthetic lethal therapeutic option. AU - Pessetto, Ziyan Yuan. AU - Yan, Ying. AU - Bessho, Tadayoshi. AU - Natarajan, Amarnath. PY - 2012/7. Y1 - 2012/7. N2 - Synthetic lethal therapeutic strategy using poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitor olaparib in carriers of BRCA1 or BRCA2 mutation has shown promise in clinical settings. Since ≤5 % of patients are BRCA1 or BRCA2 mutation carriers, small molecules that functionally mimic BRCA1 or BRCA2 mutations will extend the synthetic lethal therapeutic option for non-mutation carriers. Here we provide proof of principle for this strategy using a BRCA1 inhibitor peptide 2 that targets the BRCT(BRCA1)-phosphoprotein interaction and mimics the M177R/K BRCA1 mutation. Reciprocal immunoprecipitation and immunoblotting of BRCA1 and Abraxas was used to ...
About 5% to 10% of breast cancers are thought to be hereditary, caused by abnormal genes passed from parent to child.. Genes are particles in cells, contained in chromosomes, and made of DNA (deoxyribonucleic acid). DNA contains the instructions for building proteins. And proteins control the structure and function of all the cells that make up your body.. Most inherited cases of breast cancer are associated with two abnormal genes: BRCA1 (BReast CAncer gene one) and BRCA2 (BReast CAncer gene two).. Everyone has BRCA1 and BRCA2 genes. The function of the BRCA genes is to repair cell damage and keep breast cells growing normally. But when these genes contain abnormalities or mutations that are passed from generation to generation, the genes dont function normally and breast cancer risk increases. Abnormal BRCA1 and BRCA2 genes may account for up to 10% of all breast cancers, or 1 out of every 10 cases.. Having an abnormal BRCA1 or BRCA2 gene doesnt mean you will be diagnosed with breast cancer. ...
Given that breast cancers in germline BRCA1 carriers are predominantly estrogen-negative and triple-negative, it has been suggested that women diagnosed with triple-negative breast cancer (TNBC) younger than 50 years should be offered BRCA1 testing, regardless of family cancer characteristics. However, the predictive value of triple-negative breast cancer, when taken in the context of personal and family cancer characteristics, is unknown. The aim of this study was to determine whether TNBC is a predictor of germline BRCA1 mutations, in the context of multiple predictive factors. Germline mutations in BRCA1 and BRCA2 were analyzed by Sanger sequencing and multiple ligation-dependent probe amplification (MLPA) analysis in 431 women from the Malaysian Breast Cancer Genetic Study, including 110 women with TNBC. Logistic regression was used to identify and to estimate the predictive strength of major determinants. Estrogen receptor (ER) and phosphatase and tensin homologue (PTEN) status were assessed and
SNPedia currently contains 2606 BRCA1 SNPs and 3099 BRCA2 SNPs. Some of the variations in these genes are linked to Breast cancer and ovarian cancer, and other variations are benign. See also BRCA1 and BRCA2 for individual gene discussions and links. Microarray platforms used by DTC genomics testing companies such as FamilyTree DNA and 23andMe usually test a fraction of the known BRCA1 or BRCA2 SNPs, typically, the most common ones. While DTC genomics testing may lead to useful results, it is not a substitute for the full genetic panel testing or gene sequencing that may be warranted by a family history of breast cancer. The percent of known BRCA1 and BRCA2 syndrome disease-causing mutations that are tested by several companies is shown in the following table: ...
Men with prostate cancer who are carriers of the BRCA2 gene mutation have significantly increased mortality rates.. The study identified 938 families with the BRCA2 mutation, of which 277 (29.5%) contained one or more cases of prostate cancer, with a total of 434 cases. Of these, 67 men were found to carry the familial BRCA2 mutation and 116 were probable mutation carriers. A comparison group of men with the BRCA1 mutation was also identified. Of 1,735 families, 316 contained one or more cases of prostate cancer (18.2%), with a total of 457 cases. Of these, 37 carried the BRCA1 mutation and 82 men were probable carriers. The average age at diagnosis was similar for the two groups.. Survival analysis was performed to establish the overall survival of BRCA2 carriers with prostate cancer and relative survival compared with BRCA1 carriers. The median survival time was 4.0 years for the BRCA2 group compared with 8.0 years for the BRCA1 group, and the risk of mortality was found to be 70% greater in ...
Ataxia-telangiectasia mutation (ATM) has previously been shown to be necessary for the phosphorylation of BRCA1 to occur in response to gamma-irradiation, and capable of directly phosphorylating BRCA1 in vitro (see additional information). This paper indicates that ATM can also cause the phosphorylation of BRCA1 by activating the hCds1/CHK2 kinase, for which BRCA1 is a substrate. Phosphorylation of BRCA1 in response to other genotoxins appears to be independent of ATM (Scully et al, Cell 1997, 90: 425-435 [Abstract]). ATM-independent activation of hCds1/CHK2 may explain how some of these other genotoxins cause BRCA1 phosphorylation.. The ATM-hCds1/CHK2-BRCA1 DNA damage response pathway is clearly important for tumour suppression since heterozygous carriers of mutant BRCA1, ATM and hCds1/hCHK2 genes (see additional information) have all been reported to be predisposed to breast cancer. ...
TY - JOUR. T1 - Genetic testing in an ethnically diverse cohort of high-risk women. T2 - A comparative analysis of BRCA1 and BRCA2 mutations in American families of European and African ancestry. AU - Nanda, Rita. AU - Schumm, L. Philip. AU - Cummings, Shelly. AU - Fackenthal, James D.. AU - Sveen, Lise. AU - Ademuyiwa, Foluso. AU - Cobleigh, Melody. AU - Esserman, Laura. AU - Lindor, Noralane Morey. AU - Neuhausen, Susan L.. AU - Olopade, Olufunmilayo I.. PY - 2005/10/19. Y1 - 2005/10/19. N2 - Context: Ten years after BRCA1 and BRCA2 were first identified as major breast cancer susceptibility genes, the spectrum of mutations and modifiers of risk among many ethnic minorities remain undefined. Objectives: To characterize the clinical predictors, spectrum, and frequency of BRCA1 and BRCA2 mutations in an ethnically diverse high-risk clinic population and to evaluate the performance of the BRCAPRO statistical model in predicting the likelihood of a mutation. Design, Setting, and Participants: ...
Modular domains of proteins are important in cellular signaling processes. Eukaryotic cells are constantly undergoing DNA damage due to exogenous and endogenous sources of damage. The DNA damage response (DDR) involves a complex network of signaling events mediated by modular domains such as the BRCT (BRCA1 C-terminal) domains. Therefore, proteins containing BRCT domains are important for DNA damage detection and signaling. In this dissertation, we focus on two BRCT-containing proteins BRCA1 and PAXIP1. BRCA1 is a gene that is known to be associated with increased risk of hereditary breast and ovarian cancer. Germline variants of BRCA1 are assessed to determine lifetime risk of developing breast and ovarian cancer. This is performed by genetic testing of the BRCA1 sequence and the variants can be classified as pathogenic, non-pathogenic or variants of unknown significance (VUS). Using family history, segregation analysis, co-occurrence and tumor pathology, certain variants have been classified as either
The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific
Abnormalities caused by targeted disruption of the Brca2 gene include increased sensitivity to DNA damage induced by ionizing irradiation, UV light, and other genotoxic agents (27, 33, 34). The accumulation of double-strand DNA breaks and chromosomal abnormalities combined with the lack of obvious checkpoint or apoptotic response abnormalities in Brca2 mutant cells have implied a role of BRCA2 in DNA repair (33, 34). Recent findings that BRCA2 and RAD51 interact in vitro have suggested further that BRCA2 may be involved in RAD51-mediated repair pathways (27, 35, 36). In this study, we identified the BRCA2 gene product as a 460-kDa nuclear phosphoprotein that forms a complex with RAD51 in vivo. While this manuscript was in preparation, Chen et al. (44) reported detection of BRCA2 as a nuclear protein, consistent with our findings. They also reported detection of immunocomplexes containing BRCA2 and RAD51 (44). Our findings established that a major fraction of endogenous RAD51 is associated with ...
article{81b520fa-fde6-40e1-9977-b09909f3e717, abstract = {Inherited mutations in the tumor suppressor genes BRCA1 and BRCA2 predispose carriers to breast and ovarian cancer. The authors have identified a mutation in BRCA2, 7845+1G > A (c.7617+1G > A), not previously regarded as deleterious because of incorrect mapping of the splice junction in the originally published genomic reference sequence. This reference sequence is generally used in many laboratories and it maps the mutation 16 base pairs inside intron 15. However, according to the recent reference sequences the mutation is located in the consensus donor splice sequence. By reverse transcriptase analysis, loss of exon 15 in the final transcript interrupting the open reading frame was demonstrated. Furthermore, the mutation segregates with a cancer phenotype in 18 Danish families. By genetic analysis of more than 3,500 Danish breast/ovarian cancer risk families, the mutation was identified as the most common BRCA2 mutation in West ...
To explore the relation of BRCA1 to these foci, we assayed, for IRIF (17), HCC1937 cells that express a COOH-terminally truncated BRCA1 protein (19). BRCA1 foci were diminished in these cells, and the nuclear staining of BRCA1 was homogenous, albeit much dimmer, in HCC1937 cells regardless of treatment (Fig. 3B). Interestingly, hRad50, hMre11, and p95 IRIF were dramatically reduced in HCC1937 cells. Most of the irradiated cells displayed a diffuse nuclear pattern of hRad50, hMre11, or p95 immunostaining similar to that seen in untreated HCC1937 cells. In contrast, IRIF that were positive for hRad51 antibodies were readily and efficiently detected in both T24 and HCC1937 cells (Fig. 3B).. In addition to BRCA1 mutation, HCC1937 also harbors many other genetic changes (19). To determine whether the BRCA1 deficiency was responsible for the defect in IRIF formation, we transiently transfected hemagglutinin (HA)-tagged wild-type BRCA1 into HCC1937 cells and irradiated cells 40 hours later. Of the ...
Germline mutations in the tumor-suppressor gene BRCA2 predispose to breast and ovarian cancer. BRCA2 plays a well-established role in maintaining genome stability by regulating homologous recombination. BRCA2 has more recently been implicated in cytokinesis, the final step of cell division, but the molecular basis for this remains unknown. We have used time-lapse microscopy, recently developed cytokinesis assays and BAC recombineering (bacterial artificial chromosome recombinogenic engineering to investigate the function and localization of BRCA2 during cell division. Our analysis suggests that BRCA2 does not regulate cytokinesis in human cells. Thus, cytokinesis defects are unlikely to contribute to chromosomal instability and tumorigenesis in BRCA2-related cancers. ...
Mutation of BRCA1 and BRCA2 is the most common cause of inherited breast and ovarian cancer. Genetic screens to detect carriers of variants can aid in cancer prevention by identifying individuals with a greater cancer risk and can potentially be used to predict the responsiveness of tumours to therapy. Frequently, classification cannot be performed based on traditional approaches such as segregation analyses, including for many missense variants, which are therefore referred to as variants of uncertain significance (VUS). Functional assays provide an important alternative for classification of BRCA1 and BRCA2 VUS. As reviewed here, both of these tumour suppressors promote the maintenance of genome stability via homologous recombination. Thus, related assays may be particularly relevant to cancer risk. Progress in implementing functional assays to assess missense variants of BRCA1 and BRCA2 is considered here, along with current limitations and the path to more impactful assay systems. While ...
The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. Oxidative stress caused by reactive oxygen species (ROS) is implicated in carcinogenesis and is used strategically to treat human cancer. Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, we briefly summarize BRCA1s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers.
The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. Genome stability is compromised when cells are exposed to oxidative stress. Increasing evidence suggests that BRCA1 regulates oxidative stress and this may be another mechanism in preventing carcinogenesis in normal cells. Oxidative stress caused by reactive oxygen species (ROS) is implicated in carcinogenesis and is used strategically to treat human cancer. Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. In this review, we briefly summarize BRCA1s many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers.
A womans lifetime chance of developing breast and/or ovarian cancer is greatly increased if she inherits an altered BRCA1 or BRCA2 gene. Women with an inherited alteration in one of these genes have an increased risk of developing these cancers at a young age (before menopause), and often have multiple close family members with the disease. These women may also have an increased chance of developing colon cancer. Men with an altered BRCA1 or BRCA2 gene also have an increased risk of breast cancer (primarily if the alteration is in BRCA2), and possibly prostate cancer. Alterations in the BRCA2 gene have also been associated with an increased risk of lymphoma, melanoma, and cancers of the pancreas, gallbladder, bile duct, and stomach in some men and women.. According to estimates of lifetime risk, about 13.2 percent (132 out of 1,000 individuals) of women in the general population will develop breast cancer, compared with estimates of 36 to 85 percent (360-850 out of 1,000) of women with an ...
LOH of three intragenic BRCA1 SNPs (2201C/T, 2430T/C, and 2731C/T) that flank the mutation site was confirmed in both the primary and recurrent tumors ( Fig. 3A and B, and data not shown), indicating that contamination by nontumor cells was negligible and that both the primary and recurrent tumors had lost one BRCA1 allele. Intriguingly, in the primary tumor, both wild-type BRCA1 sequence and BRCA1 sequence with 2594delC were detected ( Fig. 3A and B). Careful laser microdissection of a separate second sample of this tumor revealed the same result. The presence of both wild-type BRCA1 sequence and mutant sequence on one allele in the primary tumor suggests that genetic reversion (back mutation to wild-type) occurred on one copy of the mutant allele. We speculate that the presence of the genetically reverted wild-type allele in the primary tumor contributed to the unusual initial platinum resistance of this tumor. The selective pressure for the genetically reverted tumor cells in the primary ...
TY - JOUR. T1 - Efficacy versus effectiveness of clinical genetic testing criteria for BRCA1 and BRCA2 hereditary mutations in incident breast cancer. AU - Nilsson, Martin P.. AU - Winter, Christof. AU - Kristoffersson, Ulf. AU - Rehn, Martin. AU - Larsson, Christer. AU - Saal, Lao H.. AU - Loman, Niklas. PY - 2017/4. Y1 - 2017/4. N2 - Increasing evidence supports the benefit of identifying BRCA1 and BRCA2 germline mutations in early breast cancer. Selection of patients for genetic testing is based on defined criteria taking individual and family history related factors into account. It is important to make a distinction between efficacy and effectiveness of BRCA testing criteria. Efficacy can be defined as the performance under ideal circumstances, whereas effectiveness refers to its real life performance. To allow for an unbiased and detailed evaluation of efficacy and effectiveness of the Swedish BRCA testing criteria, we retrospectively analyzed a prospectively collected cohort of 273 breast ...
If a parent is determined to have a germline RB1 cancer-predisposing mutation either by positive family history, by an eye examination that reveals a retinoblastoma-associated eye lesion, or by molecular genetic testing that reveals the presence of a cancer-predisposing RB1 mutation, the risk to each sib of the index case is 50% (or lower if the carrier parent is a mutational mosaic) of inheriting the cancer-predisposing RB1 mutation. Given the approximately 99% penetrance of most RB1 cancer-predisposing mutations, the actual risk for retinoblastoma in these individuals is about 50% (or lower if the carrier parent is a mutational mosaic). (Note: In rare families with "familial-low penetrance retinoblastoma," the risk of tumor development is less than 40 ...
The BRCA2 and MRE11 proteins participate in the repair of double-strand DNA breaks by homologous recombination. Germline BRCA2 mutations predispose to ovarian, breast and pancreatic cancer, while a germline MRE11 mutation is associated with an ataxia telangiectasia-like disorder. Somatic mutations of BRCA2 are rare in typical sporadic cancers. In tumors having microsatellite instability (MSI), somatic truncating mutations in a poly [A] tract of BRCA2 are reported on occasion. We analyzed gastrointestinal MSI cancers by whole gene BRCA2 sequencing, finding heterozygous truncating mutations in seven (47%) of 15 patients. There was no cellular functional defect in RAD51 focus-formation in three heterozygously mutated lines studied, although other potential functions of the BRCA2 protein could still be affected. A prior report of mutations in primary MSI tumors affecting the IVS5-(5-15) poly [T] tract of the MRE11 gene was confirmed and extended by analysis of the genomic sequence and protein expression in
Loss of heterozygosity data from familial tumors suggest that BRCA1, a gene that confers susceptibility to ovarian and early-onset breast cancer, encodes a tumor suppressor. The BRCA1 region is also subject to allelic loss in sporadic breast and ovarian cancers, an indication that BRCA1 mutations may occur somatically in these tumors. The BRCA1 coding region was examined for mutations in primary breast and ovarian tumors that show allele loss at the BRCA1 locus. Mutations were detected in 3 of 32 breast and 1 of 12 ovarian carcinomas; all four mutations were germline alterations and occurred in early-onset cancers. These results suggest that mutation of BRCA1 may not be critical in the development of the majority of breast and ovarian cancers that arise in the absence of a mutant germline allele ...
Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Ghalami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Pam K, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A, Skolnick MH. 1994. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266: 66-71 ...
Breast cancer 1, early onset (BRCA1) expression is often reduced in sporadic breast tumors, even in the absence of BRCA1 genetic modifications, but the molecular basis for this is unknown. In this study, we identified homeobox A9 (HOXA9) as a gene frequently downregulated in human breast cancers and tumor cell lines and noted that reduced HOXA9 transcript levels associated with tumor aggression, metastasis, and patient mortality. Experiments revealed that loss of HOXA9 promoted mammary epithelial cell growth and survival and perturbed tissue morphogenesis. Restoring HOXA9 expression repressed growth and survival and inhibited the malignant phenotype of breast cancer cells in culture and in a xenograft mouse model. Molecular studies showed that HOXA9 restricted breast tumor behavior by directly modulating the expression of BRCA1. Indeed, ectopic expression of wild-type BRCA1 phenocopied the tumor suppressor function of HOXA9, and reducing BRCA1 levels or function inhibited the antitumor activity ...
Breast cancer 1, early onset (BRCA1) expression is often reduced in sporadic breast tumors, even in the absence of BRCA1 genetic modifications, but the molecular basis for this is unknown. In this study, we identified homeobox A9 (HOXA9) as a gene frequently downregulated in human breast cancers and tumor cell lines and noted that reduced HOXA9 transcript levels associated with tumor aggression, metastasis, and patient mortality. Experiments revealed that loss of HOXA9 promoted mammary epithelial cell growth and survival and perturbed tissue morphogenesis. Restoring HOXA9 expression repressed growth and survival and inhibited the malignant phenotype of breast cancer cells in culture and in a xenograft mouse model. Molecular studies showed that HOXA9 restricted breast tumor behavior by directly modulating the expression of BRCA1. Indeed, ectopic expression of wild-type BRCA1 phenocopied the tumor suppressor function of HOXA9, and reducing BRCA1 levels or function inhibited the antitumor activity ...
Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04
We have characterized expression of the familial breast and ovarian cancer gene, BRCA1, in cases of non-hereditary (sporadic) breast cancer and analyzed the effect of antisense inhibition of BRCA1 on the proliferative rate of mammary epithelial cells. BRCA1 mRNA levels are markedly decreased during the transition from carcinoma in situ to invasive cancer. Experimental inhibition of BRCA1 expression with antisense oligonucleotides produced accelerated growth of normal and malignant mammary cells, but had no effect on non-mammary epithelial cells. These studies suggest that BRCA1 may normally serve as a negative regulator of mammary epithelial cell growth whose function is compromised in breast cancer either by direct mutation or alterations in gene expression ...
The BRCA1 and BRCA2 genes are the two major high-risk breast and/or ovarian cancer susceptibility genes. Monoallelic germline mutations that disrupt their normal gene function significantly increase the risk of developing cancer in carriers. The identification of a causal mutation in a proband allows proposing pre-symptomatic testing for the causal mutation to all at-risk relatives. Currently, a causal mutation, used for genetic counseling, is presented in approximatively 13% of families tested. Variants of unknown biological significance (VUS) are detected in more than 20% of proband tested. For the families of these probands, genetic testing could not be proposed to relatives and the genetic counseling is guided by family history and epidemiological knowledges exclusively.. The French UMD-BRCA1/2 database, accredited by the French National Cancer Institute, collects anonymous results of genetic tests performed by authorized French laboratories since 1995, giving a real-time vision of families ...
Estrogênio é essencial para a modulação da expressão do BRCA1. O gene BRCA1 apresenta na sua região promotora dois sítios de início de transcrição distintos, um localizado no éxon-1A e o outro no éxon-1B. O estrogênio é capaz de recrutar proteínas AP1 e o complexo receptor de estrogênio α /p300 a um sítio AP 1 adjacente ao sítio de início de transcrição do éxon 1B e de recrutar proteínas Sp (Sp1 e Sp4) há regiões próximas do sítio Ap1. Quando ocorre a ligação do estrogênio ao complexo receptor de estrogênio α /p300 há um desencadeamento de eventos de fosforilação que culminam na fosforilação do próprio complexo e de proteínas Sp que modulam a interação proteína-proteína do promotor do gene BRCA1.[16] O AhR (Aromatic hydrocarbon Receptor) é um outro importante receptor nuclear que atua na regulação da expressão de BRCA1 através de ligação direta em sua região promotora ou de forma indireta por intermédio de receptor estrogênio. Foi proposto ...
The tumor suppressor BRCA1 regulates the DNA damage response (DDR) and other processes that remain incompletely defined. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal E3 ligase activity. Here, it is demonstrated that BRCA1 promotes oxidative metabolism by degrading Oct1 (POU2F1), a transcription factor with proglycolytic and tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells toward a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNA sequencing (RNAseq) confirms deregulation of metabolic genes downstream of Oct1. BRCA1 mediates Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenograft assays. In primary breast cancer clinical specimens, Oct1 ...
During the submission of this work, a study with consistent findings was published online (27). Both studies find that the coiled-coil domain present at the NH2 terminus of PALB2 directly binds to BRCA1 and that this interaction is required for the assembly of BRCA2 foci. In contrast to the other paper, however, we define and characterize two point mutants of the coiled-coil domain that disrupt binding to BRCA1. In this manner, we more specifically implicate PALB2 as a linker of BRCA1 and BRCA2. Furthermore, we directly compare PALB2-deficient cells reconstituted with mutants defective for interaction with either BRCA1 or BRCA2. This has led to a more definitive demonstration that PALB2 links BRCA1, BRCA2, and RAD51 into a DNA damage response pathway. Additionally, using the set of reconstituted cells, we have determined that PALB2 is positioned between BRCA1 and BRCA2 in this pathway. Unlike the other article, we assay the assembly of RAD51 foci and resistance to the DNA interstrand ...
BRCA1 / RNF53, 50 µg. BRCA1 (breast and ovarian cancer susceptibility protein 1) is a RING finger protein containing a BRCT domain.
BRCA1 / RNF53, 50 µg. BRCA1 (breast and ovarian cancer susceptibility protein 1) is a RING finger protein containing a BRCT domain.
New research is showing a link between the BRCA1 gene (the "breast cancer" gene) and infertility. An article published by http://www.medicaldaily.com reports researchers from a NIH funded institute found that the BRCA1 gene, in its functional form, aided in the repair of female egg cells, keeping them from self-destruction.. As female eggs age, DNA damage occurs. The body has mechanisms to help repair these eggs, but eventually those mechanisms wear out as we age, and our eggs are no longer able to be repaired and they self-destruct. Enter menopause. However, for some women menopause occurs much earlier than anticipated and/or they are told they have relatively low egg reserve at a very young age. What causes this to occur?. Researchers looked at the role the BRCA1 gene plays in DNA repair for eggs of lab mice. In this study researchers turned off the genes, including the BRCA1 gene, associated with repairing damaged egg cells:. ...
The BRCA gene encodes for the BRCA proteins, BRCA1 and BRCA2. These proteins are very important in repairing DNA, which they do by correcting double-stranded breaks.
Next, we investigated the binding domains of BRCA1 with AKT using an in vitro binding assay. A series of four overlapping GST fusion proteins, spanning the entire coding region of BRCA1, were used to define regions of BRCA1 that interact with AKT. Purified GST-BRCA1 fusion proteins were added to MCF7 cell-free extracts, and GST-BRCA1-AKT complexes were isolated with glutathione beads. pAKT, but not unphosphorylated AKT, was found to bind fragment 1501-1861 of BRCA1 as detected by Western blotting ( Fig. 2C). BRCA1 fragment 1501-1861 contains the BRCT domains, which are phospho-protein binding domains that are important for the tumor suppressor function of BRCA1. The recombinant BRCA1-BRCT domain (residues 1599-1863) fused to GST-bound endogenous pAKT from a MCF7 cell lysate ( Fig. 2D). The cancer-associated missense mutations M1775R and P1749R in the BRCT domains of the COOH terminus of BRCA1 ablate the functions of BRCA1 ( 2). We tested the binding ability of these BRCA1 mutants to pAKT and ...
To further explore whether BRCA1 enrichment and its associated exclusion of 53BP1 from the IRIF core correlates with inhibition of 53BP1-dependent repair at DSB sites during S phase, we analysed cells recovering from acute treatment with camptothecin (CPT), a topoisomerase I inhibitor that induces DSBs in S phase when replication forks encounter trapped Top1-DNA cleavage complexes (Pommier et al., 2003). In BRCA1-deficient cells, CPT-induced chromosomal aberrations are 53BP1 dependent; indicating BRCA1 normally counteracts 53BP1-mediated repair activities in this context (Bunting et al., 2010). Consistent with this notion, CPT-induced foci closely resembled S-phase IRIF by 3D-SIM, with BRCA1 and 53BP1 adopting equivalent focal positions (Fig. 4C). The repair of DSBs by HR in S phase also relies on CtIP-mediated DNA-end resection (Sartori et al., 2007). Consistent with a model in which the focus core corresponds to sites of HR in S-phase cells, 3D-SIM analysis of CtIP localisation in irradiated ...
Patients with GBM tumors expressing low levels of BRCA1 were demonstrated to be associated with prolonged survival when compared with GBM patients with tumors expressing higher levels of the proteins - median overall survival was found to be 18.9 vs 4.8 months, respectively.. Archived tissue microarrays of tumor samples isolated from 66 GBM patients who had participated in Radiation Therapy Oncology Group clinical trials underwent analysis for RAD51, BRCA1, PTEN, and miRNA-210 protein expression. These 66 patients had all been treated with surgery, radiotherapy and non-temozolomide chemotherapy, and had a similar overall survival.. "BRCA1 is a tumor suppressor gene that is involved in DNA repair. Mutations of this gene, or deficient protein due to epigenetic changes, lead to DNA damage repair failure," explained the studys principal investigator Maria Vasilakopoulou (Pitié-Salpêtrière Hospital, Paris, France). "The study results suggest strongly that low BRCA1 protein expression in the GBM ...
INTRODUCTION: Preservation of structure and function of the myocardium is critically dependent upon improving the survival of existing cardiomyocytes (CM), through strategies that limit CM apoptosis and DNA damage. BRCA1 is a tumor suppressor gene which functions to promote DNA repair, and protect cells against oxidative and genotoxic stress. We hypothesized that BRCA1 is a novel cellular target to limit CM apoptosis, and prevent aberrant cardiac remodeling.. METHODS AND RESULTS: Experimental MI in mice caused a profound 16-fold upregulation in BRCA1 expression, which peaked at 72 hours (p,0.01). In vitro gain-of-function experiments demonstrated that Ad-BRCA1 overexpression protected neonatal rat CM against doxorubicin- and H2O2-induced apoptosis, as assessed by FACS (p,0.01) and activated caspase-3. Ad-BRCA1-expressing CM exhibited a profound reduction in p53 expression in response to doxorubicin and H2O2. Co-immunoprecipitation studies demonstrated a distinct physical interaction of BRCA1 ...
Ali, A.B., Iau, P.T.C., Sng, J.-H. (2010). Cancer-specific methylation in the BRCA1 promoter in sporadic breast tumours. Medical Oncology 28 (1) : 64-66. [email protected] Repository. https://doi.org/10.1007/s12032-010-9438- ...
Purpose: Breast cancers in carriers of inactivating mutations of the BRCA1 gene carry a specific DNA copy-number signature ("BRCA1-like"). This signature is shared with cancers that inactivate BRCA1 through other mechanisms. Because BRCA1 is important in repair of DNA double-strand breaks through error-free homologous recombination, patients with a BRCA1-like tumor may benefit from high-dose alkylating (HD) chemotherapy, which induces DNA double-strand breaks.. Experimental Design: We investigated a single institution cohort of high-risk patients that received tandem HD chemotherapy schedule comprising ifosfamide, epirubicin, and carboplatin or conventional chemotherapy. We classified copy-number profiles to be BRCA1-like or non-BRCA1-like and analyzed clinical associations and performed survival analysis with a treatment by biomarker interaction design.. Results: BRCA1-like status associated with high-grade and triple-negative breast cancers. BRCA1-like cases benefitted from the HD compared ...
A pair of studies could change the way patients are evaluated for mutations of BRCA1 and BRCA2, two cancer susceptibility genes closely associated with breast and ovarian cancers, as well as other tumor types.
The c.213-12A,G variant in BRCA1 has been reported in ,25 individuals with BRCA1 -associated cancers and segregated with disease in 4 affected relatives from 2 f amilies (Dong 1998, Hoffman 1998, Meindl 2002, Thirthagiri 2008, Kast 2012, de J uan Jimenez 2013, Brohet 2014,Breast Cancer Information Core (BIC) database). Th is variant was absent from large population studies. In vitro functional studies provide evidence that the c.213-12A,G variant introduces a cryptic splice site, causing an additional 11 nucleotides to be retained and leading to a frameshift , which alters the protein?s amino acid sequence beginning at position 71 and le ads to a premature termination codon 21 amino acids downstream (Hoffman 1998, Me nendez 2012). This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA1 gene is an established dise ase mechanism in hereditary breast and ovarian cancer (HBOC). In summary, this v ariant meets our criteria to be ...
Homologous recombination (HR) is essential for the accurate repair of DNA double-strand breaks (DSBs), potentially lethal lesions. HR takes place in the late S-G2 phase of the cell cycle and involves the generation of a single-stranded region of DNA, followed by strand invasion, formation of a Holliday junction, DNA synthesis using the intact strand as a template, branch migration and resolution. It is investigated that RecA/Rad51 family proteins play a central role. The breast cancer susceptibility protein Brca2 and the RecQ helicase BLM (Bloom syndrome mutated) are tumor suppressors that maintain genome integrity, at least in part, through HR ...
Homologous recombination (HR) is essential for the accurate repair of DNA double-strand breaks (DSBs), potentially lethal lesions. HR takes place in the late S-G2 phase of the cell cycle and involves the generation of a single-stranded region of DNA, followed by strand invasion, formation of a Holliday junction, DNA synthesis using the intact strand as a template, branch migration and resolution. It is investigated that RecA/Rad51 family proteins play a central role. The breast cancer susceptibility protein Brca2 and the RecQ helicase BLM (Bloom syndrome mutated) are tumor suppressors that maintain genome integrity, at least in part, through HR ...
This gene encodes a protein which interacts with the N-terminal region of BRCA1. In addition to its ability to bind BRCA1 in vivo and in vitro, it shares homology with the 2 most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes. This protein also contains 3 tandem ankyrin repeats. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. This protein may be the target of oncogenic mutations in breast or ovarian cancer. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013] ...
This guideline includes statements and recommendations based on available evidence about the management of early breast cancer in women with an identified BRCA1 or BRCA2 gene mutation or at high risk of such a gene mutation predisposing to breast cancer. The guideline provides health professionals with information designed to assist in making management recommendations for
For years, researchers have known that under normal conditions, the breast cancer protein BRCA1 orchestrates the repair of damaged DNA, but the details of just how BRCA1 moves to the damaged site and recruits the right nuclear repairmen for DNA restoration remains a mystery. Now, a new study from the University of Pennsylvania School of Medicine has identified genes associated with the BRCA1 protein and their involvement in the DNA repair pathway, helping to clear the way for researchers to better understand what goes wrong when the BRCA1 gene is mutated and the repair pathway goes haywire. Identifying patients with mutations in these BRCA1-associated genes may help better fight breast cancer.
Furuya, F., Poitelea, M., Guo, L., Caspari, T. and Carr, A. M. (2004) Chk1 activation requires Rad9 S/TQ-site phosphorylation to promote association with C-terminal BRCT domains of Rad4TOPBP1. Genes and Development, 18. pp. 1154-1164. ISSN 0890-9369 Full text not available from this repository ...
TY - JOUR. T1 - Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations. T2 - A case-control study. AU - Kotsopoulos, Joanne. AU - Librach, Clifford L.. AU - Lubinski, Jan. AU - Gronwald, Jacek. AU - Kim-Sing, Charmaine. AU - Ghadirian, Parviz. AU - Lynch, Henry T.. AU - Moller, Pal. AU - Foulkes, William D.. AU - Randall, Susan. AU - Manoukian, Siranoush. AU - Pasini, Barbara. AU - Tung, Nadine. AU - Ainsworth, Peter J.. AU - Cummings, Shelly. AU - Sun, Ping. AU - Narod, Steven A.. AU - Horsman, D.. AU - Rosen, B.. AU - Isaacs, C.. AU - Domchek, S.. AU - Gershoni-Baruch, R.. AU - Eisen, A.. AU - Olopade, O. I.. AU - Friedman, E.. AU - Saal, H. M.. AU - Neuhausen, S. L.. AU - Daly, M.. AU - Karlan, B.. AU - Kurz, R. N.. AU - Bellati, C.. AU - Eng, C.. AU - Sweet, K.. AU - Wagner, T.. AU - Rennert, G.. AU - Provencher, D.. AU - Maugard, C.. AU - Garber, J.. AU - McKinnon, W.. AU - Wood, M.. AU - Gilchrist, D.. AU - Osborne, M.. AU - ...
The most frequent contributors to hereditary cancer risk in human population so far are the inherited mutations in the BRCA1 or BRCA2 tumor suppressor genes.
Many companies hold gene patents, so why sue Myriad? The answer is simple: in the battle of public opinion, theres no way Myriad can come out of this looking good. A bit of recent history: the BRCA1 gene was famously mapped by a group led by Mary-Claire King, currently at the University of Washington. That group, however, narrowed down the location of the gene only to a relatively large region, and the gene itself was finally isolated months later and patented by Myriad (BRCA2 came later). Myriad did the obvious--they designed a test for a series of mutations in the genes and began to market it. However, the series of mutations they test is not the whole story--other mutations, untested by Myriad, can cause the disease as well. Other labs would be happy to market tests for these mutations, except, of course, that Myriad refuses to license its patent, preferring instead to hold onto their monopoly on the gene. The result: families that would like to be tested for rare mutations in BRCA1 but an ...
During the past decade it has been shown that alternative splicing is a important mechanism for the proteome diversity. AS is a mechanism that generates a large amount of protein isoforms from a low number of human genes. Alternative splicing is regulated by four groups of cis-regulatory elements and different splicing factors. Even though AS is important for the diversity and complexity of different organisms it is also a source for different genetic diseases like cancer. This review article will focus on breast cancer and its connection to the mechanism of alternative splicing. Breast cancer is a common disease in women. In recent years many studies have shown an important relationship between mutations in the alternative splicing mechanism and the two most important genes involved in breast cancer BRCA1 and BRCA2. This article will also present different efforts against this disease. ...
Differential sensitivity among BRCA1-defective and BRCA1-competent cells to Tax. In (A) HCC1937 cells, (B) MCF-7 cells and (C) MDA-MB231 cells, the dose-related
FUNCTION: [Summary is not available for the mouse gene. This summary is for the human ortholog.] Inherited mutations in BRCA1 and this gene, BRCA2, confer increased lifetime risk of developing breast or ovarian cancer. Both BRCA1 and BRCA2 are involved in maintenance of genome stability, specifically the homologous recombination pathway for double-strand DNA repair. The BRCA2 protein contains several copies of a 70 aa motif called the BRC motif, and these motifs mediate binding to the RAD51 recombinase which functions in DNA repair. BRCA2 is considered a tumor suppressor gene, as tumors with BRCA2 mutations generally exhibit loss of heterozygosity (LOH) of the wild-type allele. [provided by RefSeq, Dec 2008 ...
Silencing of BRCA1, by promoter methylation, decreased expression by gene deletion, or dysregulation of relevant genes in the Fanconi anemia BRCA1 pathway, is believed to become essential during the pathogenesis of the important proportion of sporadic tumors. Preclinical work has proven the amount of BRCA1 protein expression correlates with chemosensitivity, and latest clinical information supports that BRCA1 deficient OC sufferers have a much better prognosis. Very low BRCA1 protein and mRNA expression has also been linked with improved survival in breast cancer and non smaller cell lung cancer. The improved final result in BRCA1 deficient tumors is believed to be due, in element, to an increased sensitivity to DNA damaging che motherapeutics, for example cisplatin.. Cells that lack BRCA1 possess a deficiency while in the fix of double strand breaks through the conservative mechanism of homologous recombination. As a consequence, these inhibitor expert cancer cells are reduced to using error ...
Purpose: Most BRCA1/2 mutations are of unknown clinical relevance. An increasing amount of evidence indicates that there can be deleterious effects through the disruption of the splicing process. We have investigated the effect of aberrant splicing of BRCA1/2 on hereditary breast/ovarian cancer (HBOC).. Experimental Design: DNA variants were analyzed with splicing prediction programs to select putative splicing mutations. Splicing assays of 57 genetic variants were done by lymphocyte reverse transcription-PCR and/or hybrid minigenes in HeLa and nontumor breast epithelial cells.. Results: Twenty-four BRCA1/2 variants of Spanish HBOC patients were bioinformatically preselected. Functional assays showed that 12 variants induced anomalous splicing patterns, 6 of which accounted for 58.5% of BRCA1 families. To further evaluate the defective splicing of BRCA1/2, we analyzed 31 Breast Cancer Information Core Database (BIC) and two artificial variants that were generated by mutagenesis. Sixteen variants ...
This genetic epidemiology study reports that risk of breast and ovarian cancer among women with BRCA1 and BRCA2 mutations varies by mutation type and location.
BRCA stands for breast cancer susceptibility genes, a class of genes known as tumor suppressors. Mutations have been linked to hereditary br…
Members of the Rad51 protein family are highly homologous to bacterial RecA and Saccharomyces cerevisiae Rad51. These proteins are involved in the homologous recombination and repair of double-stranded breaks in DNA. Rad51 can interact with the ssDNA-binding protein RPA and Rad52. Rad51 also interacts with products of two genes implicated in susceptibility to breast cancer, BRCA1 and BRCA2. In particular, BRCA2 protein is shown to regulate both the intracellular localization and DNA-binding ability of Rad51. Inactivation of BRCA2 leads to loss of Rad51-mediated transcriptional control, and this inactivation may be central to genomic instability and tumorigenesis. Rad51 is also known as RAD51 homolog (S. cerevisiae); RAD51 homolog (RecA homolog, E. coli); BRCA1/BRCA2-containing complex, subunit 5; RECA, BRCC5, MRMV2, HRAD51, RAD51A, HsRad51, and HsT16930.. ...
Members of the Rad51 protein family are highly homologous to bacterial RecA and Saccharomyces cerevisiae Rad51. These proteins are involved in the homologous recombination and repair of double-stranded breaks in DNA. Rad51 can interact with the ssDNA-binding protein RPA and Rad52. Rad51 also interacts with products of two genes implicated in susceptibility to breast cancer, BRCA1 and BRCA2. In particular, BRCA2 protein is shown to regulate both the intracellular localization and DNA-binding ability of Rad51. Inactivation of BRCA2 leads to loss of Rad51-mediated transcriptional control, and this inactivation may be central to genomic instability and tumorigenesis. Rad51 is also known as RAD51 homolog (S. cerevisiae); RAD51 homolog (RecA homolog, E. coli); BRCA1/BRCA2-containing complex, subunit 5; RECA, BRCC5, MRMV2, HRAD51, RAD51A, HsRad51, and HsT16930.. ...
Dr. Patricia Tonin is a Professor in the Departments of Medicine and Human Genetics, and Associate Member in the Program for Cancer Genetics of the Department of Oncology and the Goodman Cancer Research Centre at McGill University. Dr. Tonins research focuses on the identification of cancer-predisposing genes, such as BRCA1 and BRCA2, and their contribution to the hereditary form of breast and ovarian cancers. Her research has led to the development of genetic tests for identifying women at risk for cancer for management and prevention options. Her research also focuses on the biology of ovarian cancer through the study of the molecular genomic attributes of cancer specimens and cell line models. As a member of the Banque de tissus et de données (cancer du sein ou ovaire) of the Réseau de Recherche sur le Cancer du Fonds de recherche du Québec - Santé, she oversees the organization of DNA samples collected from familial cases of breast and ovarian cancer for researching hereditary ...
NCI-funded research helped identify inherited BRCA1 and BRCA2 genetic mutations and their connection to breast and ovarian cancer. From this research, a screening test was also developed to help patients make informed decisions about their health.
Dave told me about his sisters and his mothers breast cancer experiences and his sisters diagnosis when she was only 30 years old. His grandmother had died in her 50s from breast cancer. In the first year that we were dating, I talked a lot with his mother about BRCA and genetic testing, and eventually he, his sister, his mother, and his uncle all had the test and discovered that they were positive for the BRCA1 mutation. - Bryna Siegel Finer, Philadelphia Inquirer and Daily News
Dr. Tezcan responded: Yes. Brca1 and 2 mutation analysis is performed at myriad lab in usa. One can either use an oral swab or blood for testing. It is strongly recommended that the testing is done in the context of |a href="/topics/genetic-counseling" track_data="{
多种适用的BRCA1ELISA试剂盒,如小鸡, Cow, 犬等。在antibodies-online.cn对比BRCA1ELISA试剂盒,以便找到您需要的产品。
The Bold Type has been tackling important cultural issues from the get go. Including from race, LGBTQ identity, to womens health. For example last season, after losing her mom to breast cancer, Jane tested positive for a gene mutation called BRCA,…
Detect and quantitate human BRCA2 in serum, buffered solution, and cell culture supernatants using a homogeneous AlphaLISA no-wash assay.
Cells carrying mutated BRCA1 or BRCA2 genes are defective in DNA repair by homologous recombination and, as a consequence, are highly sensitive to inhibitors of poly (ADP-ribose) polymerase (PARP). This provides the basis for a novel "synthetic lethal" approach to cancer therapy. We have recently shown that this sensitivity can be reversed, and resistance to PARP inhibition can be acquired by deletion of a mutation in BRCA2. Furthermore, a similar mechanism seems to be associated with carboplatin resistance in some BRCA2 mutation carriers with ovarian cancer. (Cancer Res 2008;68(24):10021-3]. ...
... , Authors: Frédéric Guénard, Francine Durocher. Published in: Atlas Genet Cytogenet Oncol Haematol.
Dr. Mary-Claire King, the cancer geneticist who discovered BRCA1, explains how that discovery has forever changed breast cancer prevention and treatment.
Zimmer J, Tacconi EM, Folio C, Badie S, Porru M, Klare K, Tumiati M, Markkanen E, Halder S, Ryan A, Jackson SP, Ramadan K, Kuznetsov SG, Biroccio A, Sale JE, Tarsounas M. Molecular Cell 61, 449-460. G-quadruplex (G4)-forming genomic sequences, including telomeres, represent natural replication fork barriers. Stalled replication forks can be stabilized and restarted by homologous recombination (HR), which also repairs DNA double-strand breaks (DSBs) arising at collapsed forks.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies. ...
12 months after Aussie designer Camilla Franks completed treatment for breast cancer, shes hit yet another speed bump on her journey to recovery: the new mum has learned shes inherited the BRCA1 gene mutation, resulting in an operation to remove her ovaries.
New knowledge about the normal function of the BRCA1 gene, various mutations of which have been shown to cause breast and ovarian cancers, may help researchers develop treatments for both hereditary and sporadic disease. Jeffrey T. 1
Recombinant BRCA1 is suitable for in vitro studies of transcription and DNA repair, for protein-protein interaction assays and cell growth assays.
Factsheets on biomarkers prepared by esteemed European experts with statements on prognostic and predictive value, testing recommendations, and more
rs77542170, also known as both c.925-2A,G and c.934-2A,G, represents a rare variant in the MUTYH gene on chromosome 1. Inherited recessively, the minor allele is considered in ClinVar (and BabySeq) as a pathogenic mutation for a cancer-predisposing syndrome, autosomal recessive familial adenomatous polyposis-2 (FAP2). Affected individuals have a significantly higher risk of developing colorectal cancer. ...
This page includes the following topics and synonyms: Carcinogens in the Workplace, Occupational Exposures Linked to Cancer, Cancer-predisposing Occupational Exposure.
BRCA1 Antibody - N-terminal region (AVARP02017_P050) |2 Images| 2 Online protocols|Applications: IHC, WB|Species reactivity: Dog, Human, Rat|Type: Rabbit polyclonal antibody
BRCA1兔多克隆抗体(ab3614)可与人样本反应并经WB实验严格验证。中国75%以上现货,所有产品均提供质保服务,可通过电话、电邮或微信获得本地专属技术支持。
File:Figure2D BarlowCell.tiff First researchers needed to map early replication origins in an activated B-cell genome. To do this they performing ChIP with anti-replication protein A (RPA). They harvested fresh mouse splenic B-cells, stimulated them with LPS/IL4 to enter cell cycle. They then inhibited replication in G1/S phase using hydroxyurea (HU) allowing RPA binds to ssDNA at stalled forks. In addition to RPA, the researchers looked for the localization of recombination proteins BRCA1 and SMC5 to regions also occupied by RPA in order to identify regions in which the fork was not only stalled but had collapsed and required homologous recombination repair. From this ChIP data, they were able to identify 2204 regions were RPA, BRCA1, and SMC5 were all localized (Figure 1D). Upon further characterization of the 2204 regions, it was found that they contained shared common elements such as highly repetitive sequences (e.g. LINE L2, SINE, DNA transposon, and tRNA elements) which are known fork ...
These reference sequences exist independently of genome builds. Explain. These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above. ...
This study will evaluate the efficacy and safety of 6MP in combination with methotrexate in patients with breast or ovarian cancer who are known to have
Few black women aged 50 years or younger eligible for genetic testing for breast cancer had been referred for such testing or genetic counseling.
Genomically selected treatment has demonstrated unequivocal benefit and has thus been incorporated into routine management of at least seven different solid tumors as well as several types of leukemia. In total, 11 genomic biomarkers are part of health authority prescribing indications, including ALK, BCR-ABL1, BRAF, BRCA1, BRCA2, EGFR, ERBB2, KIT, PDGFRA, PDGFRB, and ROS1 (1). Moreover, a growing list of promising investigational biomarkers is being actively pursued in clinical trials. What remains to be answered, therefore, is not whether genome-driven oncology can work but rather what proportion of patients will ultimately benefit from this approach and for how long.. To answer this crucial question, several drug-development centers have launched broad genomic screening programs to facilitate hypothesis-driven enrollment onto precision oncology studies (2). The utility of this strategy will be best demonstrated by the successful development of new treatments targeting specific alterations, in ...
Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. Also acts as a Ras responsive E3 ubiquitin ligase that, on activation of Ras, is modified by auto-polyubiquitination resulting in the release of inhibition of Raf/MEK complex formation. May also act as a cytoplasmic retention protein with a role in regulating nuclear transport ...
The PDB archive contains information about experimentally-determined structures of proteins, nucleic acids, and complex assemblies. As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
In chapter 3, "The Sense of Sensibility," author Wendy Jones uses scenes from one of Jane Austens most celebrated novels to illustrate the functioning of the bodys stress response system.. 0 Comments. ...
Daily News How Gaining and Losing Weight Affects the Body Millions of measurements from 23 people who consumed extra calories every day for a month reveal changes in proteins, metabolites, and gut microbiota that accompany shifts in body mass.. ...
癌症的形成,與某些基因的突變,有極強的關聯性。乳癌患者所生的女兒,罹患乳癌的機率大幅升高,而基因突變所導致家族遺傳性乳癌,佔所有乳癌的一部份(約10%)。BRCA-1是ㄧ種抑癌基因,其功能與p53類似,可以調控細胞週期,並負責斷裂DNA的修補。15-20%有乳癌家族病史的婦女,與60-80%有乳癌及卵巢癌兩種家族病史的婦女,可以發現有BRCA-1基因的突變。帶有BRCA1突變基因被診斷出
Long before Angelina Jolie told the world that she had tested positive for a mutation in the BRCA1 gene and why she decided to remove her breasts and ovaries, Huntsman Cancer Institute was using genetic testing to identify people at increased risk for canc
Affiliation (Current):地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所),その他部局等,技師・研究員, Research Field:Pathological medical chemistry,Tumor biology,Tumor biology,General medical chemistry, Keywords:BRCA2,乳癌,DNA損傷修復,DR-GFP,U2OS,画像認識,タンパク質間相互作用,遺伝子破壊,Rad18,Ubc13, # of Research Projects:5, # of Research Products:25, Ongoing Project:DNA修復と中心体複製異常を指標にしたBRCAの分子内発癌抑制責任部位の特定
pep:known chromosome:VEGA66:5:140705066:140719379:1 gene:OTTMUSG00000024801 transcript:OTTMUST00000061083 gene_biotype:protein_coding transcript_biotype:protein_coding gene_symbol:Brat1 description:BRCA1-associated ATM activator 1 ...
The DsiRNA Design or Catalog ID # appears on the DsiRNA ordering webpage and on your DsiRNA spec sheet. IDT uses this sequence identifier to track what gene the DsiRNA targets and the actual sequence ordered. Its nomenclature is designed to provide information about the sequence.. DsiRNAs designed and ordered since February 2016. Example Design ID # hs.Ri.BRCA1.13.2:. ...
Looking for online definition of BRCA1/BRCA2-containing complex, subunit 1 in the Medical Dictionary? BRCA1/BRCA2-containing complex, subunit 1 explanation free. What is BRCA1/BRCA2-containing complex, subunit 1? Meaning of BRCA1/BRCA2-containing complex, subunit 1 medical term. What does BRCA1/BRCA2-containing complex, subunit 1 mean?
Background: While BRCA mutation carriers possess a 20-40% lifetime risk of developing ovarian cancer, knowledge about genetic modifying factors influencing the phenotypic expression remains obscure. We explored the distribution of the MDM2 polymorphisms SNP309T>G and the recently discovered SNP285G>C in Norwegian patients with BRCA related ovarian cancer.. G and the recently discovered SNP285G>C in Norwegian patients with BRCA related ovarian cancer.. C in Norwegian patients with BRCA related ovarian cancer.. Methods: 221 BRCA related ovarian cancer cases (BRCA1; n = 161 and BRCA2; n = 60) were tested for the MDM2 polymorphisms. Results were compared to healthy controls (n = 2,465).. Results: The SNP309G allele was associated with elevated OR for ovarian cancer in BRCA1 mutation carriers (SNP309TG: OR 1.53; CI 1.07-2.19; p = 0.020; SNP309GG: OR 1.92; CI 1.19-3.10; p = 0.009; SNP309TG+GG combined: OR 1.61; CI 1.15-2.27; p = 0.005). In contrast, the SNP285C allele reduced risk of BRCA1 related ...
PURPOSE: We analyzed the expression of critical cell cycle regulators cyclin E and cyclin D1 in familial breast cancer, focusing on BRCA mutation-negative tumors. Cyclin E expression in tumors of BRCA1 or BRCA2 carriers is higher, and cyclin D1 expression lower, than in sporadic tumors. In familial non-BRCA1/2 tumors, cyclin E and cyclin D1 expression has not been studied. EXPERIMENTAL DESIGN: Cyclin E and cyclin D1 immunohistochemical expression was studied in tissue microarrays consisting of 53 BRCA1, 58 BRCA2, 798 familial non-BRCA1/2, and 439 sporadic breast tumors. RESULTS: In univariate analysis, BRCA1 tumors had significantly more frequently high cyclin E (88%) and low cyclin D1 (84%) expression than sporadic (54% and 49%, respectively) or familial non-BRCA1/2 (38% and 45%, respectively) tumors. BRCA2 tumors had significantly more frequently low cyclin D1 expression (68%) than sporadic or familial non-BRCA1/2 tumors and significantly more frequently high cyclin E expression than familial ...
An analysis of the GeparSixto trial in triple-negative breast cancer showed that adding carboplatin to neoadjuvant therapy improved pathologic complete response rate in patients without BRCA1/2 mutation and that response rates were higher overall in those with mutations, without additive effects observed for carboplatin. The analysis was reported by Hahnen et al in JAMA Oncology. GeparSixto showed the addition of neoadjuvant carboplatin to anthracycline, taxane, and bevacizumab (Avastin) increased pathologic complete response rates among all patients.. Study Details The current analysis included 291 patients, of whom 146 received carboplatin. Pathogenic BRCA1 and BRCA2 germline mutations were present in 50 patients (17.2%), including 26 patients who received carboplatin and 24 patients who did not.. Pathologic Complete Response Rate. The pathologic complete response rate was 56.8% in the carboplatin group vs 41.4% in the group that did not receive carboplatin (odds ratio [OR] = 1.87, P = .009). ...
TY - JOUR. T1 - Endometrial cancers in mutation carriers from hereditary breast ovarian cancer syndrome kindreds. AU - Casey, Murray J.. AU - Bewtra, Chhanda. AU - Lynch, Henry T.. AU - Snyder, Carrie L.. AU - Stacey, Mark. PY - 2015/5/7. Y1 - 2015/5/7. N2 - Objective The aim of this study was to categorize and report endometrial cancers in mutation carriers from hereditary breast ovarian cancer families. Methods Our Hereditary Cancer Registry was searched for gynecologic and peritoneal cancers linked to mutations in BRCA1 or BRCA2. Invasive cancers were registered in 101 mutation carriers with complete pathology reports. Efforts were made to secure diagnostic surgical pathology tissues for review. All records and available diagnostic slides were meticulously studied, and primary cancers were classified. Findings Eight malignancies were classified as primary endometrial cancers. Five of these were low- or intermediate-grade endometrioid carcinomas, and 3 were pure serous carcinomas or contained ...
Recognition of early changes in the Fallopian tube cells of BRCA gene mutation carriers may be key to new strategies for preventing ovarian cancer that could also reduce the need for invasive surgery.
BACKGROUND: Breast cancer (BC) is primarily considered a genetic disorder with a complex interplay of factors including age, gender, ethnicity, family history, personal history and lifestyle with associated hormonal and non-hormonal risk factors. The SNP rs2910164 in miR146a (a G to C polymorphism) was previously associated with increased risk of BC in cases with at least a single copy of the C allele in breast cancer, though results in other cancers and populations have shown significant variation. METHODS: In this study, we examined this SNP in an Australian sporadic breast cancer population of 160 cases and matched controls, with a replicate population of 403 breast cancer cases using High Resolution Melting. RESULTS: Our analysis indicated that the rs2910164 polymorphism is associated with breast cancer risk in both primary and replicate populations (p=0.03 and 0.0013, respectively). In contrast to the results of familial breast cancer studies, however, we found that the presence of the G allele of
Women with hereditary breast cancer predispositions should avoid using their smartphones, tablets and laptops at night Home Women with hereditary breast cancer predispositions should avoid using their smartphones, tablets and laptops at night 09 JAN 18 Women with hereditary breast cancer predispositions should avoid using their smartphones, tablets and laptops at night From SMJ Mortazavi,…
Metalloprotease that specifically cleaves Lys-63-linked polyubiquitin chains (PubMed:19214193, PubMed:20656690, PubMed:24075985, PubMed:26344097). Does not have activity toward Lys-48-linked polyubiquitin chains. Component of the BRCA1-A complex, a complex that specifically recognizes Lys-63-linked ubiquitinated histones H2A and H2AX at DNA lesions sites, leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). In the BRCA1-A complex, it specifically removes Lys-63-linked ubiquitin on histones H2A and H2AX, antagonizing the RNF8-dependent ubiquitination at double-strand breaks (DSBs) (PubMed:20656690). Catalytic subunit of the BRISC complex, a multiprotein complex that specifically cleaves Lys-63-linked ubiquitin in various substrates (PubMed:20656690, PubMed:24075985, PubMed:26344097, PubMed:26195665). Mediates the specific Lys-63-specific deubiquitination associated with the COP9 signalosome complex (CSN), via the interaction of the BRISC complex

The Human Protein AtlasThe Human Protein Atlas

... namely the BRCA1 and BRCA2 genes. Women with abnormal BRCA1 or BRCA2 have higher risk of developing breast cancer...Read more ... Protein class. Chromosome. External id. - DATA AVAILABILITY -. Has protein data. - DATA RELIABILITY -. Reliability score tissue ... Protein evidence (Ezkurdia et al 2014). Protein evidence (Kim et al 2014). RAS pathway related proteins. Ribosomal proteins. ... Conference Diagnostics Human Protein Atlas Life Science Pathology Pathology Atlas This weekend Amsterdam is hosting the 29th ...
more infohttp://v16.proteinatlas.org/blog/pathology-atlas

Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance | PNASStabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance | PNAS

Finally, concomitant increased mutant BRCA1 and decreased 53BP1 protein expression occur in clinical samples of BRCA1-mutated ... Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance. Neil Johnson, Shawn F. Johnson, Wei Yao, ... Stabilization of mutant BRCA1 protein confers PARP inhibitor and platinum resistance Message Subject (Your Name) has sent you a ... involving heat shock protein (HSP)90-mediated stabilization of the mutant protein coupled with tumor protein p53 binding ...
more infohttps://www.pnas.org/content/110/42/17041.abstract

Suppression of tumor growth by the BRCA1-associated protein-1 | ScienceBlogsSuppression of tumor growth by the BRCA1-associated protein-1' | ScienceBlogs

BRCA1-associated protein-1), was recently accepted for publication in the journal Cancer Research. ... I am happy to report that my research paper on a protein implicated in breast and lung cancer, called BAP1 ( ... I am happy to report that my research paper on a protein implicated in breast and lung cancer, called BAP1 (BRCA1-associated ... Weirdly, I have very good associations with BRCA1 -- doing a project on BRCA1 orthologs was my first encounter with fiery spiny ...
more infohttps://scienceblogs.com/sciencetolife/2008/07/02/suppression-of-tumor-growth-by

Brca1 - BRCA1 - Rattus norvegicus (Rat) - Brca1 gene & proteinBrca1 - BRCA1 - Rattus norvegicus (Rat) - Brca1 gene & protein

View protein in InterPro. IPR011364. BRCA1. IPR031099. BRCA1-associated. IPR025994. BRCA1_serine_dom. ... View protein in InterPro. IPR011364. BRCA1. IPR031099. BRCA1-associated. IPR025994. BRCA1_serine_dom. ... to allow unambiguous identification of a protein.,p>,a href=/help/protein_names target=_top>More...,/a>,/p>Protein namesi. ... tr,Q9JKL6,Q9JKL6_RAT BRCA1 (Fragment) OS=Rattus norvegicus GN=Brca1 PE=2 SV=1 ...
more infohttp://www.uniprot.org/uniprot/Q9JKL6

Researchers discover how breast cancer mutation in BRCA1 causes protein to self-destruct | EurekAlert! Science NewsResearchers discover how breast cancer mutation in BRCA1 causes protein to self-destruct | EurekAlert! Science News

Tech Carilion Research Institute found that breast cancer cells can trigger the self-destruction of the tumor-suppressing BRCA1 ... They suspect that the BRCA1 mutation causes a small misfolding that allows even more ubiquitin to attach to the protein. ... Cells tag the mutated BRCA1 protein for destruction with a molecule called ubiquitin, according to Kelly. The cells then ... Researchers discover how breast cancer mutation in BRCA1 causes protein to self-destruct Genetic mutation disarms tumor ...
more infohttps://www.eurekalert.org/pub_releases/2017-02/vt-rdh022417.php

BRCA1-associated protein 1 | definition of BRCA1-associated protein 1 by Medical dictionaryBRCA1-associated protein 1 | definition of BRCA1-associated protein 1 by Medical dictionary

What is BRCA1-associated protein 1? Meaning of BRCA1-associated protein 1 medical term. What does BRCA1-associated protein 1 ... Looking for online definition of BRCA1-associated protein 1 in the Medical Dictionary? BRCA1-associated protein 1 explanation ... BRCA1-associated protein 1 , definition of BRCA1-associated protein 1 by Medical dictionary https://medical-dictionary. ... redirected from BRCA1-associated protein 1) BAP1. A gene on chromosome 3p21.31-p21.2 that encodes a tumour-suppressing enzyme ...
more infohttp://medical-dictionary.thefreedictionary.com/BRCA1-associated+protein+1

brcc3 Protein, BRCA1/BRCA2-containing complex, subunit 3 - Creative BioMartbrcc3 Protein, BRCA1/BRCA2-containing complex, subunit 3 - Creative BioMart

This complex plays a role in the DNA damage response, where it is responsible for the stable accumulation of BRCA1 at DNA break ... This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. ... Recombinant Human BRCC3 Protein, GST-tagged. Wheat Germ. Human. GST. +Inquiry. BRCC3-2481M. Recombinant Mouse BRCC3 Protein. ... Recombinant Human BRCC3 protein, His-tagged. E. coli. Human. His. +Inquiry. BRCC3-328H. ...
more infohttps://www.creativebiomart.net/symbolsearch_BRCC3.htm

BRCA1 Recombinant Human ProteinBRCA1 Recombinant Human Protein

Recombinant BRCA1 is suitable for in vitro function studies including transcription and DNA repair, for protein-protein ... Research proven and tested recombinant human BRCA1 protein. ... C-Reactive Protein. PR27090. 1 mg. C-Reactive Protein. PR27090 ... The BRCA1Protein is and tumor suppressor and is directly involved in DNA repair. Mutations in the BRCA1 gene have been ... Storage: Lyophilized proteins can be stored at 4°C. As a recombinant protein, store at -80°C. Avoid freeze-thaw cycles. ...
more infohttps://www.neuromics.com/PR26000

An Insilico Drug Designing Approach to Target the BRCA1 Protein involved in Breast cancer - HelixAn Insilico Drug Designing Approach to Target the BRCA1 Protein involved in Breast cancer - Helix

An Insilico Drug Designing Approach to Target the BRCA1 Protein involved in Breast cancer. Home / 2018 / January / 9 / An ... BRCA1 are the human genes and it has a protein product respectively. It is responsible for the repairing of the DNA. The cross ... ROLE OF BRCA1 GENE: It provides a instructions to make a protein which acts a tumor suppressor. Tumor suppressor proteins helps ... Thus this compound can be used as a better drug in targeting the BRCA1 protein as a means to control cell division. ...
more infohttp://helix.dnares.in/2018/01/09/an-insilico-drug-designing-approach-to-target-the-brca1-protein-involved-in-breast-cancer/

RCSB PDB - Protein Feature View 









 - Breast cancer type 1 susceptibility protein - P38398 (BRCA1 HUMAN)RCSB PDB - Protein Feature View - Breast cancer type 1 susceptibility protein - P38398 (BRCA1 HUMAN)

The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates ... which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex (PubMed:10783165). This ... Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/ ... Protein Feature View of PDB entries mapped to a UniProtKB sequence * Number of PDB entries for Q3LRJ6: no matching PDB entries ...
more infohttp://www.rcsb.org/pdb/protein/Q3LRJ6

Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein by RAPTA complexes and its E3 ubiquitin...Biochemical and biophysical characterization of ruthenation of BRCA1 RING protein by RAPTA complexes and its E3 ubiquitin...

The binding of the RAPTA compounds to the BRCA1 protein resulted in a release of Zn2+ ions in a dose and time dependent manner ... In this study, the interaction of some RAPTA compounds with the N-terminal fragment of the BRCA1 RING domain protein was ... These findings could provide mechanistic insight into the mode of action of RAPTA complexes for on tested BRCA1 model protein ... residues 44-49 and 55 on full length BRCA1). Changes in the conformation and binding constants of ruthenium-BRCA1 adducts were ...
more infohttps://infoscience.epfl.ch/record/229566

RCSB PDB - Protein Feature View 









 - BRCA1-A complex subunit RAP80 - Q96RL1 (UIMC1 HUMAN)RCSB PDB - Protein Feature View - BRCA1-A complex subunit RAP80 - Q96RL1 (UIMC1 HUMAN)

... at least composed of the BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/NBA1. In the BRCA1-A complex, ... leading to target the BRCA1-BARD1 heterodimer to sites of DNA damage at double-strand breaks (DSBs). The BRCA1-A complex also ... This protein in other organisms (by gene name): Q96RL1 - Homo sapiens 4 * Q9BZR1 - Homo sapiens no matching PDB entries ... Protein disorder predictions are based on JRONN (Troshin, P. and Barton, G. J. unpublished), a Java implementation of RONN * ...
more infohttp://www.rcsb.org/pdb/protein/Q96RL1

BRCA1-associated proteinBRCA1-associated protein

The protein encoded by this gene was identified by its ability to bind to the nuclear localization signal of BRCA1 and other ... Prognostic significance of BRCA1-associated protein 1 in colorectal cancer.. 23356535. 2013. Lack of association between a ... The BRCA1-binding protein BRAP2 can act as a cytoplasmic retention factor for nuclear and nuclear envelope-localizing ... Interactome of the negative regulator of nuclear import BRCA1-binding protein 2.. ...
more infohttps://pharos.nih.gov/idg/targets/Q7Z569

Abstract 613: The chromatin remodeling protein BRG1 modulates BRCA1s response to UV irradiation. | Cancer ResearchAbstract 613: The chromatin remodeling protein BRG1 modulates BRCA1's response to UV irradiation. | Cancer Research

Abstract 613: The chromatin remodeling protein BRG1 modulates BRCA1s response to UV irradiation.. Ling Zhang, Hua Chen and ... The chromatin remodeling protein BRG1 modulates BRCA1s response to UV irradiation. [abstract]. In: Proceedings of the 104th ... Abstract 613: The chromatin remodeling protein BRG1 modulates BRCA1s response to UV irradiation. ... Abstract 613: The chromatin remodeling protein BRG1 modulates BRCA1s response to UV irradiation. ...
more infohttp://cancerres.aacrjournals.org/content/73/8_Supplement/613

BRCA1 185delAG mutant protein, BRAt, amplifies caspase-mediated apopto by Joshua D. ODonnell"BRCA1 185delAG mutant protein, BRAt, amplifies caspase-mediated apopto" by Joshua D. O'Donnell

IOSE cell lines carrying the BRCA1 185delAG mutation showed higher maspin levels than wild-type BRCA1 IOSE cell lines. BRCA1 ... Here, we report on the transfection of cDNA coding for the putative truncated protein product of the BRCA1 185delAG mutant gene ... Additionally, both heterozygous carriers of the BRCA1 185delAG mutation and cells transfected with BRAt protein show an ... Cells transfected with the BRCA1 185delAG truncation protein (BRAt) showed increased levels of active caspase 3, increased ...
more infohttp://scholarcommons.usf.edu/etd/433/

Link Between BRCA1 Gene And ATM Protein May Explain Increased Breast Cancer Risk (dateline November 11, 1999) | Breast Health...Link Between BRCA1 Gene And ATM Protein May Explain Increased Breast Cancer Risk (dateline November 11, 1999) | Breast Health...

Texas have discovered that the protein kinase ATM (ataxia telangiecta ... In this case, BRCA1 must rely on the ATM protein to initiate the repairs. ATM is important in recognizing when chromosomes are ... The new study reveals that BRCA1 may rely on the ATM protein to repair some types of cell damage. When DNA damage occurs in ... Link Between BRCA1 Gene And ATM Protein May Explain Increased Breast Cancer Risk (dateline November 11, 1999). ...
more infohttp://www.imaginis.com/breast-health-news/link-between-brca1-gene-and-atm-protein-may-explain-increased-breast-cancer-risk-dateline-november-1

Tissue expression of BRCA1 - Staining in kidney - The Human Protein AtlasTissue expression of BRCA1 - Staining in kidney - The Human Protein Atlas

Expression of BRCA1 (BRCC1, FANCS, PPP1R53, RNF53) in kidney tissue. Antibody staining with HPA034966, HPA057371 and CAB001946 ... Protein expressioni. The protein expression bar, with the units not detected (n), low (l), medium (m) and high (h), is based on ... Protein class. Chromosome. External id. - DATA AVAILABILITY -. Has protein data. - DATA RELIABILITY -. Reliability score tissue ... Protein evidence (Ezkurdia et al 2014). Protein evidence (Kim et al 2014). RAS pathway related proteins. Ribosomal proteins. ...
more infohttp://www.proteinatlas.org/ENSG00000012048-BRCA1/tissue/kidney

Tissue expression of BRCA1 - Staining in prostate - The Human Protein AtlasTissue expression of BRCA1 - Staining in prostate - The Human Protein Atlas

Expression of BRCA1 (BRCC1, FANCS, PPP1R53, RNF53) in prostate tissue. Antibody staining with HPA034966, HPA057371 and ... Protein expressioni. The protein expression bar, with the units not detected (n), low (l), medium (m) and high (h), is based on ... Protein class. Chromosome. External id. - DATA AVAILABILITY -. Has protein data. - DATA RELIABILITY -. Reliability score tissue ... Protein evidence (Ezkurdia et al 2014). Protein evidence (Kim et al 2014). RAS pathway related proteins. Ribosomal proteins. ...
more infohttp://www.proteinatlas.org/ENSG00000012048-BRCA1/tissue/prostate

RCSB PDB - Protein Feature View 









 - Breast cancer type 1 susceptibility protein - P38398 (BRCA1 HUMAN)RCSB PDB - Protein Feature View - Breast cancer type 1 susceptibility protein - P38398 (BRCA1 HUMAN)

The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates ... which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex (PubMed:10783165). This ... Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/ ... This protein in other organisms (by gene name): P38398 - Homo sapiens 28 * Q60983 - Mus musculus no matching PDB entries ...
more infohttp://bioinformatics.sdsc.edu/pdb/protein/P38398?chromosome=chr17&range=43106478&v=hg38

RCSB PDB - Protein Feature View 









 - Breast cancer type 1 susceptibility protein - P38398 (BRCA1 HUMAN)RCSB PDB - Protein Feature View - Breast cancer type 1 susceptibility protein - P38398 (BRCA1 HUMAN)

The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. The BRCA1-BARD1 heterodimer coordinates ... which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the MRE11-RAD50-NBN protein (MRN) complex (PubMed:10783165). This ... Component of the BRCA1-A complex, at least composed of BRCA1, BARD1, UIMC1/RAP80, ABRAXAS1, BRCC3/BRCC36, BABAM2 and BABAM1/ ... This protein in other organisms (by gene name): P38398 - Homo sapiens 28 * Q60983 - Mus musculus no matching PDB entries ...
more infohttp://bioinformatics.sdsc.edu/pdb/protein/P38398

Human Breast cancer susceptibility protein 1 (BRCA1) ELISA KitHuman Breast cancer susceptibility protein 1 (BRCA1) ELISA Kit

You need info about Human Breast cancer susceptibility protein 1 (BRCA1) ELISA Kit or any other Gentaur produtct? Contact us on ... Human (Homo sapiens) BRCA1 elisa. Shipping, handling and storage. The kit is shipped on ice packs. Upon receiving it store the ... Detects Human (Homo sapiens) BRCA1; Additional information. ...
more infohttps://www.gentaurshop.com/product/2684291/human-breast-cancer-susceptibility-protein-1-brca1

Recombinant Breast Cancer Susceptibility Protein 1 (BRCA1), Recombinant protein, CLOUD-CLONE CORP.(CCC)Recombinant Breast Cancer Susceptibility Protein 1 (BRCA1), Recombinant protein, CLOUD-CLONE CORP.(CCC)

BRCA1), Homo sapiens (Human), Recombinant protein, BRCAI, BRCC1, IRIS, PSCP, RNF53, Breast Cancer 1,Early Onset, RING finger ... Recombinant Breast Cancer Susceptibility Protein 1 (BRCA1) BRCAI; BRCC1; IRIS; PSCP; RNF53; Breast Cancer 1,Early Onset; RING ... If bio-activity of the protein is needed, please check active protein.. Research use only ... The loss rate was determined by accelerated thermal degradation test, that is, incubate the protein at 37°C for 48h, and no ...
more infohttps://www.cloud-clone.us/protein/Breast-Cancer-Susceptibility-Protein-1-BRCA1-23470.htm

BRCA1-associated protein 1 deficiency in lung adenocarcinoma predicts poor outcome and increased tumor invasion | BMC Cancer |...BRCA1-associated protein 1 deficiency in lung adenocarcinoma predicts poor outcome and increased tumor invasion | BMC Cancer |...

BRCA1-associated protein-1 (BAP1) is a newly identified tumor suppressor that regulates a number of cellular functions in ... BRCA1-associated protein-1 (BAP1), is a 729aa protein and UCH family member, which exerts its DUB function via binding to the ... BAP1, BRCA1-associated protein-1; BRCA1, breast cancer 1; BSA, bovine serum albumin; CCK-8, Cell Counting Kit-8; DFS, disease ... Prognostic significance of BRCA1-associated protein 1 in colorectal cancer. Med Oncol. 2013;30(2):541.View ArticlePubMedGoogle ...
more infohttps://bmccancer.biomedcentral.com/articles/10.1186/s12885-016-2670-x

Ataxia Telangiectasia-related Protein Is Involved in the Phosphorylation of BRCA1 following Deoxyribonucleic Acid Damage |...Ataxia Telangiectasia-related Protein Is Involved in the Phosphorylation of BRCA1 following Deoxyribonucleic Acid Damage |...

Ataxia Telangiectasia-related Protein Is Involved in the Phosphorylation of BRCA1 following Deoxyribonucleic Acid Damage. ... BRCA1 protein is hyperphosphorylated following various DNA-damaging events. Here, we report that the ataxia telangiectasia ... Ataxia Telangiectasia-related Protein Is Involved in the Phosphorylation of BRCA1 following Deoxyribonucleic Acid Damage ... In supporting that BRCA1 is a substrate of ATR, we have shown that multiple fragments of BRCA1 can be phosphorylated by ATR in ...
more infohttp://cancerres.aacrjournals.org/content/60/18/5037
  • Component of the BRCA1 -A complex, at least composed of BRCA1 , BARD1 , UIMC1 /RAP80, ABRAXAS1 , BRCC3 / BRCC3 6, BABAM2 and BABAM1 /NBA1 (PubMed:19261746, PubMed:19261748, PubMed:19261749, PubMed:20351172). (rcsb.org)
  • Component of the BRCA1 -A complex, at least composed of the BRCA1 , BARD1 , UIMC1 /RAP80, ABRAXAS1 , BRCC3 / BRCC3 6, BABAM2 and BABAM1 /NBA1. (rcsb.org)
  • Here, we report on the transfection of cDNA coding for the putative truncated protein product of the BRCA1 185delAG mutant gene into BRCA1 wild-type human immortalized ovarian surface epithelial (IOSE) cells and ovarian cancer cells. (usf.edu)
  • Homology Modeling is also known as the comparative modeling of a protein which refers to the construction of the atomic resolution model of the target protein from the known or given amino acid sequences and an three dimensional structure of a related homologous protein. (dnares.in)
  • Many of these functions are linked to protein:protein interactions involving different portions of the 1,863 amino acid (aa) BRCA1 protein. (nih.gov)
  • However, BRCA1 expression is frequently reduced or absent in sporadic cancers, suggesting a much wider role in mammary carcinogenesis. (nih.gov)
  • Elucidation of the precise molecular functions of the BRCA1 gene product will greatly enhance our understanding of the pathogenesis of hereditary as well as sporadic mammary carcinogenesis. (nih.gov)
  • Since BRCA1 was cloned in 1994, its molecular function has been the subject of intense investigation. (nih.gov)
  • Electron Transfer Dissociation (ETD) fragmentation mass spectrometry revealed the preferential binding sites of the RAPTA complexes on the BRCA1 zinc finger RING domain at a similar short peptide stretch, Cys(24)Lys(25)Phe(26)Cys(27)Met(28)Leu(29) and Lys(35) (residues 44-49 and 55 on full length BRCA1). (epfl.ch)
  • The BRCA1 RING motif is flanked by alpha helices formed by residues 8-22 and 81-96 of the BRCA1 protein. (wikipedia.org)
  • These findings could provide mechanistic insight into the mode of action of RAPTA complexes for on tested BRCA1 model protein. (epfl.ch)
  • Negatively regulates MAP kinase activation by limiting the formation of Raf/MEK complexes probably by inactivation of the KSR1 scaffold protein. (nih.gov)
  • Part of the BRCA1 -associated genome surveillance complex (BASC), which contains BRCA1 , MSH2 , MSH6 , MLH1 , ATM , BLM , PMS2 and the MRE11 - RAD50 - NBN protein (MRN) complex (PubMed:10783165). (rcsb.org)
  • BRCA1 combines with other tumor suppressors, DNA damage sensors and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). (wikipedia.org)
  • Cells transfected with the BRCA1 185delAG truncation protein (BRAt) showed increased levels of active caspase 3, increased cleavage of caspase 3 substrates, PARP and DFF45, and decreased XIAP and cIAP1 following staurosporine (STS) treatment. (usf.edu)
  • It has been shown that the structure of a protein are more conserved than the sequences of the protein of the homologous, but the sequences which falls below the 20% sequence identity can have very different structure. (dnares.in)
  • We assessed the effects of missense mutants on different stages of BRCA1-mediated DNA repair by homologous recombination using chicken lymphoblastoid DT40 cells as a model system. (sigmaaldrich.com)
  • The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map). (wikipedia.org)
  • In this study, the interaction of some RAPTA compounds with the N-terminal fragment of the BRCA1 RING domain protein was investigated. (epfl.ch)
  • Component of the BRCA1 - RBBP8 complex (PubMed:16101277). (rcsb.org)
  • the interaction ubiquitinates RBBP8 , regulates CHEK1 activation, and involves RBBP8 in BRCA1 -dependent G2/M checkpoint control on DNA damage (PubMed:16818604, PubMed:9811458). (rcsb.org)
  • We initially examined whether wortmannin, a potent inhibitor of PI3K, would inhibit BRCA1 hyperphosphorylation following γ radiation. (aacrjournals.org)
  • In contrast, two phosphorylated forms of BRCA1 do not accumulate at sites of UV damage. (aacrjournals.org)
  • Similarly, maspin protein has been shown to sensitize breast carcinoma cells to STS-induced apoptosis. (usf.edu)
  • These domains encode approximately 27% of BRCA1 protein. (wikipedia.org)
  • There are six known isoforms of BRCA1, with isoforms 1 and 2 comprising 1863 amino acids each. (wikipedia.org)
  • It was shown recently that BRCA1 contributes to UV damage response by promoting photoproduct excision, triggering post-UV checkpoint activation and post replicative repair. (aacrjournals.org)
  • The new study reveals that BRCA1 may rely on the ATM protein to repair some types of cell damage. (imaginis.com)
  • When DNA damage occurs in cells, BRCA1 helps the body repair those cells-a process that may prevent tumor development. (imaginis.com)
  • However, BRCA1 cannot begin the process of repairing cells when the damage is caused by some types of radiation therapies . (imaginis.com)
  • Taken together, these results suggest that ATR directly phosphorylates BRCA1 following DNA damage. (aacrjournals.org)