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)
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.
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)
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)
Tumors or cancer of the human BREAST.
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.
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.
An individual having different alleles at one or more loci regarding a specific character.
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
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.
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.
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.
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.
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.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
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.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A diverse group of proteins whose genetic MUTATIONS have been associated with the chromosomal instability syndrome FANCONI ANEMIA. Many of these proteins play important roles in protecting CELLS against OXIDATIVE STRESS.
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.
Any neoplasms of the male breast. These occur infrequently in males in developed countries, the incidence being about 1% of that in females.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Transport proteins that carry specific substances in the blood or across cell membranes.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Poly(deoxyribonucleotide):poly(deoxyribonucleotide)ligases. Enzymes that catalyze the joining of preformed deoxyribonucleotides in phosphodiester linkage during genetic processes during repair of a single-stranded break in duplex DNA. The class includes both EC 6.5.1.1 (ATP) and EC 6.5.1.2 (NAD).
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)
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.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
Biochemical identification of mutational changes in a nucleotide sequence.
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.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.
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.
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.
ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.
A polynucleotide formed from the ADP-RIBOSE moiety of nicotinamide-adenine dinucleotide (NAD) by POLY(ADP-RIBOSE) POLYMERASES.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
A genus of fleas in the family Pulicidae which includes the species that serves as the primary vector of BUBONIC PLAGUE, Xenopsylla cheopis.
Substances used to destroy or inhibit the action of rats, mice, or other rodents.
The reduction or regulation of the population of noxious, destructive, or dangerous rodents through chemical, biological, or other means.
A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.
A publication issued at stated, more or less regular, intervals.
"The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.
The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... Ekblad CM, Friedler A, Veprintsev D, Weinberg RL, Itzhaki LS (Mar 2004). "Comparison of BRCT domains of BRCA1 and 53BP1: a ... "Entrez Gene: TP53BP1 tumor protein p53 binding protein 1". Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der ...
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... The TP53 gene is the most frequently mutated gene (>50%) in human cancer, indicating that the TP53 gene plays a crucial role in ... Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN (January 1999). "The second BRCT domain of BRCA1 proteins interacts with p53 ... Ekblad CM, Friedler A, Veprintsev D, Weinberg RL, Itzhaki LS (March 2004). "Comparison of BRCT domains of BRCA1 and 53BP1: a ...
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... gene. The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of ... "Mutational analysis of the BRCA1-interacting genes ZNF350/ZBRK1 and BRIP1/BACH1 among BRCA1 and BRCA2-negative probands from ...
CtIP binds to the BRCT repeats within the breast cancer gene BRCA1 and enables CtBP to influence BRCA1 activity. Both proteins ... 1999). "Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA ... "Binding of CtIP to the BRCT repeats of BRCA1 involved in the transcription regulation of p21 is disrupted upon DNA damage". J. ... C-terminal-binding protein 1 also known as CtBP1 is a protein that in humans is encoded by the CTBP1 gene. CtBP1 is one of two ...
Rodriguez M, Yu X, Chen J, Songyang Z (2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is ... Bai S, He B, Wilson EM (2005). "Melanoma antigen gene protein MAGE-11 regulates androgen receptor function by modulating the ... "Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor". Cancer Res. 60 (21): 5946-9. PMID ...
... is vital in the rapid relocation of BRCA1 to DNA damage sites.[13] BARD1 tandem BRCA1 C-terminus (BRCT) motifs fold into ... BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.[5][6][7] The human BARD1 ... "Entrez Gene: BARD1 BRCA1 associated RING domain 1".. *^ Fox, David; Le Trong, Isolde; Rajagopal, Ponni; Brzovic, Peter S.; ... BRCA1-A complex. • BRCA1-BARD1 complex. • ubiquitin ligase complex. • cell nucleus. • nucleoplasm. • nuclear speck. • ...
Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... "Entrez Gene: KIF1B kinesin family member 1B". Bunn, R C; Jensen M A; Reed B C (April 1999). "Protein Interactions with the ... Kinesin-like protein KIF1B is a protein that in humans is encoded by the KIF1B gene. It is associated with Charcot-Marie-Tooth ... Gong TL, Burmeister M, Lomax MI (1997). "The novel gene D4Mil1e maps to mouse chromosome 4 and human chromosome 1p36". Mamm. ...
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes Dev. 16 (5): 583-93. doi ... BRCA1 is a human tumor suppressor gene (also known as a caretaker gene) and is responsible for repairing DNA. BRCA1 and BRCA2 ... BRCA1 interacts with the NELF-B (COBRA1) subunit of the NELF complex. Certain variations of the BRCA1 gene lead to an increased ... BRCA1 Protein at the US National Library of Medicine Medical Subject Headings (MeSH) Genes, BRCA1 at the US National Library of ...
Shen Y, Tong L (May 2008). "Structural evidence for direct interactions between the BRCT domains of human BRCA1 and a phospho- ... Acetyl-CoA carboxylase 1 also known as ACC-alpha or ACCa is an enzyme that in humans is encoded by the ACACA gene. Acetyl-CoA ... "Entrez Gene: acetyl-Coenzyme A carboxylase alpha". CS1 maint: discouraged parameter (link) Abu-Elheiga L, Jayakumar A, Baldini ... There are two ACC forms, alpha and beta, encoded by two different genes. ACC-alpha is highly enriched in lipogenic tissues. The ...
Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (1998). "The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a ... This gene is thought to escape X inactivation. Two transcript variants encoding the same protein have been found for this gene ... two members of a novel cdc2/CDC28-related protein kinase gene family". Oncogene. 7 (11): 2249-58. PMID 1437147. "Entrez Gene: ... The protein encoded by this gene belongs to the cdc2/cdkx subfamily of the ser/thr family of protein kinases. It may play a ...
Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... "Entrez Gene: CTCFL CCCTC-binding factor (zinc finger protein)-like". Klenova EM, Morse HC, Ohlsson R, Lobanenkov VV (2003). " ... 2005). "Reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter coincides with derepression of this cancer-testis gene in ... FactorBook CTCFL Human CTCFL genome location and CTCFL gene details page in the UCSC Genome Browser. v t e. ...
Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... "Entrez Gene: CENPC1 centromere protein C 1". Human CENPC genome location and CENPC gene details page in the UCSC Genome Browser ... Centromere protein C 1 is a protein that in humans is encoded by the CENPC1 gene. Centromere protein C 1 is a centromere ... Genes Cells. 9 (2): 105-20. doi:10.1111/j.1365-2443.2004.00705.x. PMID 15009096. S2CID 21813024. Chung TL, Hsiao HH, Yeh YY, et ...
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure». Genes Dev. 16 (5): 583-93. PMC ... O gene BRCA1 apresenta penetrância incompleta. No caso do câncer de mama as mutações no gene BRCA1 apresentam uma penetrância ... Mutações encontradas no gene do BRCA1[editar , editar código-fonte]. Espectro de mutações deletérias em BRCA1 (n=57) e BRCA2 (n ... BRCA1 (em inglês, breast cancer 1, early onset) é um gene humano pertencente a classe dos genes supressores de tumor conservado ...
Yamane K, Tsuruo T (Sep 1999). "Conserved BRCT regions of TopBP1 and of the tumor suppressor BRCA1 bind strand breaks and ... DNA topoisomerase 2-binding protein 1 is an enzyme that in humans is encoded by the TOPBP1 gene. This gene encodes a binding ... "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) ... "Entrez Gene: TOPBP1 topoisomerase (DNA) II binding protein 1". ElInati E, Russell HR, Ojarikre OA, Sangrithi M, Hirota T, de ...
Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (1998). "The C-terminal (BRCT) domains of BRCA1 interact in vivo with CtIP, a ... It is suggested that this gene may itself be a tumor suppressor acting in the same pathway as BRCA1. Three transcript variants ... Yu X, Wu LC, Bowcock AM, Aronheim A, Baer R (September 1998). "The C-terminal (BRCT) domains of BRCA1 interact in vivo with ... Rodriguez M, Yu X, Chen J, Songyang Z (Dec 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains ...
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes Dev. 16 (5): 583-93. doi ... "BRCA1 gene tree". Ensembl.. *^ Duncan JA, Reeves JR, Cooke TG (October 1998). "BRCA1 and BRCA2 proteins: roles in health and ... Gene locationEdit. The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair ... BRCT domainsEdit. The dual repeat BRCT domain of the BRCA1 protein is an elongated structure approximately 70 Å long and 30-35 ...
Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... "Entrez Gene: HDAC10 histone deacetylase 10". Fischer, Denise D; Cai Richard; Bhatia Umesh; Asselbergs Fred A M; Song Chuanzheng ... Histone deacetylase 10 is an enzyme that in humans is encoded by the HDAC10 gene. Acetylation of histone core particles ... 2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome ...
... a super complex of BRCA1-associated proteins involved in the recognition and repair of aberrant DNA structures". Genes Dev. 14 ... NBS1 relocates to DSB sites by interaction of FHA/BRCT domains with phosphorylated histone H2AX. Once it interacts with nibrin ... Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is ... Zhong Q, Chen CF, Li S, Chen Y, Wang CC, Xiao J, Chen PL, Sharp ZD, Lee WH (July 1999). "Association of BRCA1 with the hRad50- ...
Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... Yin X, Rozakis-Adcock M (2002). "Genomic organization and expression of the human tumorous imaginal disc (TID1) gene". Gene. ... "Entrez Gene: DNAJA3 DnaJ (Hsp40) homolog, subfamily A, member 3". Ng, AC; Baird, SD; Screaton, RA (April 2014). "Essential role ... 2001). "A mouse homologue of the Drosophila tumor suppressor l(2)tid gene defines a novel Ras GTPase-activating protein (RasGAP ...
The Rad9 protein contains a carboxy-terminal tandem repeat of the BRCT (BRCA1 carboxyl terminus) motif, which is found in many ... Rad9 can also regulate transcription of the base excision repair gene NEIL by binding p53-like response elements in the gene ... "Entrez Gene: RAD9A RAD9 homolog A (S. pombe)". Hwang BJ, Jin J, Gunther R, Madabushi A, Shi G, Wilson GM, Lu AL (July 2015). " ... This gene product is highly similar to S. pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA ...
This protein also goes by the name Nuclear Factor with BRCT Domain 1 (NFBD1). The MDC1 gene encodes the MDC1 nuclear protein ... Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... BRCT domain The BRCT domain on MDC1 directly binds to the γH2AX of damaged chromatin. The BRCT domain creates an α/β fold which ... The BRCT domain is involved in the regulation of the decatenation checkpoint at the end of replication by binding Topo IIα this ...
Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ (Jun 2002). "Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase". The ... Ivanova VS, Hatch CL, Bonner WM (Sep 1994). "Characterization of the human histone H2A.X gene. Comparison of its promoter with ... "NBS1 localizes to γH2AX foci through interaction with the FHA/BRCT domain". Current Biology. 12 (21): 1846-51. doi:10.1016/ ... Ivanova VS, Zimonjic D, Popescu N, Bonner WM (Sep 1994). "Chromosomal localization of the human histone H2A.X gene to 11q23.2- ...
Chai YL, Cui J, Shao N, Shyam E, Reddy P, Rao VN (January 1999). "The second BRCT domain of BRCA1 proteins interacts with p53 ... Mutations in this gene cause Rubinstein-Taybi syndrome (RTS). Chromosomal translocations involving this gene have been ... CREB-binding protein, also known as CREBBP or CBP, is a protein that in humans is encoded by the CREBBP gene. The CREB protein ... "Entrez Gene: CREBBP (CREB-binding protein)". Siddique H, Rao VN, Reddy ES (August 2009). "CBP-mediated post-translational N- ...
Rodriguez M, Yu X, Chen J, Songyang Z (2004). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) domains". J. ... "Entrez Gene: HDAC8 histone deacetylase 8". Haberland M, Mokalled MH, Montgomery RL, Olson EN (July 2009). "Epigenetic control ... The protein encoded by this gene belongs to class I of the histone deacetylase/acuc/apha family. It has histone deacetylase ... Histone deacetylase 8 is an enzyme that in humans is encoded by the HDAC8 gene. Histones play a critical role in ...
Rodriguez M, Yu X, Chen J, Songyang Z (December 2003). "Phosphopeptide binding specificities of BRCA1 COOH-terminal (BRCT) ... Mutations to the p53 gene are often found in many types of cancers. The MAP4K4 gene contains four binding sites for p53. Upon ... Hao JM, Chen JZ, Sui HM, Si-Ma XQ, Li GQ, Liu C, Li JL, Ding YQ, Li JM (March 2010). "A five-gene signature as a potential ... p53 is a tumour suppressor gene and is involved with cellular response to stress. When expressed, the cell cycle is halted in ...
BRCT domeen===. Kaksikkordus BRCT domeenis BRCA1 valgus on pikendatud struktuur, mis on umbes 70 [[ongström,ongströmi]] pikk ja ... ref name="''Donovan''",O'DONOVAN, P. J. & LIVINGSTON, D. M. (2010) BRCA1 and BRCA2:breast/ovarian cancer susceptibility gene ... BRCA1-Associated Genome Surveillance Complex'') ehk BRCA1 seotud [[genoom]]i järelevalve kompleks. BRCA1 valk seostub [[ ... O'DONOVAN, P. J. & LIVINGSTON, D. M. (2010) BRCA1 and BRCA2:breast/ovarian cancer susceptibility gene products and participants ...
Dpb11 had two pairs of BRCA1 C Terminus (BRCT) domains which are known as a phosphopeptide-binding domains. The N-terminal pair ... Asf1 (and its partner Rtt109) has also been implicated in inhibiting gene expression from replicated genes during S-phase. The ... Hennessy KM, Lee A, Chen E, Botstein D (June 1991). "A group of interacting yeast DNA replication genes". Genes & Development. ... Watson J, Baker T, Bell S, Gann A, Levine M, Losick R, Molecular Biology of the Gene 6th Edition, Pearson Education Inc, 2008. ...
RNA polymerase II subunit A C-terminal domain phosphatase is an enzyme that in humans is encoded by the CTDP1 gene. This gene ... Scully, R; Anderson S F; Chao D M; Wei W; Ye L; Young R A; Livingston D M; Parvin J D (May 1997). "BRCA1 is a component of the ... 2003). "The BRCT domain is a phospho-protein binding domain". Science. 302 (5645): 639-42. Bibcode:2003Sci...302..639Y. doi: ... 1997). "BRCA1 is a component of the RNA polymerase II holoenzyme". Proc. Natl. Acad. Sci. U.S.A. 94 (11): 5605-10. Bibcode: ...
Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is ... Kang CH, Jang BG, Kim DW, Chung DH, Kim YT, Jheon S, Sung SW, Kim JH (2010). "The prognostic significance of ERCC1, BRCA1, ... Taylor RM, Wickstead B, Cronin S, Caldecott KW (Jul 1998). "Role of a BRCT domain in the interaction of DNA ligase III-alpha ... "Complementation of repair gene mutations on the hemizygous chromosome 9 in CHO: a third repair gene on human chromosome 19". ...
Other MCPH genes[edit]. In addition to MCPH1, other genes have been designated MCPH genes based on their role in brain size. ... C-terminal BRCT domain. Expression in the brain[edit]. MCPH1 is expressed in the fetal brain, in the developing forebrain, and ... CDK5RAP and BRCA1 not associated with general cognition, reading or language". Intelligence. 36 (6): 689-93. doi:10.1016/j. ... and common genetic variants within both the MCPH1 gene and another similarly studied microcephaly gene, CDK5RAP2.[12] ...
Author Summary Promiscuous proteins are commonly observed in biological systems, such as modular domains that recognize phosphopeptides during signal transduction. The use of phosphopeptides and compounds with phosphate groups as inhibitors to protein-protein interactions have attracted increasing interest for years. By using atomistic molecular dynamics simulations, we are able to perform detailed analyses of the dihedral space to explore protein fluctuation upon ligand binding to better understand promiscuous molecular recognition. Free energy calculation can further provide insights into the mechanism of binding, including both enthalpic and entropic contributions for molecular recognition, which assist in inhibitor design. Our calculation results show that pre-rigidifying a ligand is not always advantageous, suggesting the challenge in retaining optimized intermolecular interactions in pre-rigidified ligand. Instead, certain flexible ligands with multiple binding conformations can reduce entropic
... gene. HDR is substantially reduced in Brca1SF/SF ES cells. HDR in Atm−/− ES cells has no significant difference from WT cells, ... Brca1S1598F (Brca1SF), carrying a mutation in the BRCA1 C-terminal (BRCT) domain (31). We present evidence that ATM is critical ... Brca1Δ11/Δ11 mice that express the exon 10-12 spliced product of BRCA1 with an intact BRCT domain die during embryogenesis (36 ... Brca1SF/SF mice show a less penetrant phenotype than Brca1Δ11/Δ11 mice: Brca1SF/SF mice can be recovered, but they were ...
Impact of BRCA1 BRCT domain missense substitutions on phospho-peptide recognition: R1699Q ... Gene Names: BRCA1 (RNF53). EC: 2.3.2.27. Find proteins for P38398 (Homo sapiens) ... Impact of BRCA1 BRCT Domain Missense Substitutions on Phosphopeptide Recognition.. Coquelle, N., Green, R., Glover, J.N.. (2011 ... The BRCA1 BRCT domain binds pSer-x-x-Phe motifs in partner proteins to regulate the cellular response to DNA damage. ...
... considering the two variants as a single mutation of BRCT domain. 201 differentially expressed genes were found in M1775RvsWT- ... This is in line with the very recently suggested role of BRCT domain as the main effector of BRCA1 tumor suppressor activity. ... both located in the second BRCT (BRCA1 C Terminus) domain, have been investigated. Both these variants were isolated from ... Most of these genes mapped in pathways deregulated in cancer, such as cell cycle progression and DNA damage response and repair ...
2-5), but it remains unknown how BRCA1 function is limited to the S and G2 phases. We show that BRCA1 recruitment requires ... We identify the ankyrin repeat domain of BRCA1-associated RING domain protein 1 (BARD1)-the obligate BRCA1 binding partner3-as ... show that DNA repair pathway choice and initiation of homologous recombination is guided by the recruitment of BRCA1 to post- ... Collectively, this reveals that BRCA1-BARD1 monitors the replicative state of the genome to oppose 53BP1 function, routing only ...
Gene-, Name. Start. End. Subsequence. Logic. PDB. Organism. Length. ELMI001257. Q8WXE1 ATRIP. ATRIP_HUMAN 238. 242. VVIKPEA ... Phosphorylation of S239 in the BRCT-binding motif of ATR-interacting protein (ATRIP) induces binding to the Breast cancer type ...
BRCA1_1 (click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions). Acc., Gene-, Name. Start ... BRCT_BRCA1_2 LIG_BRCT_MDC1_1 ELM Description:. The LIG_BRCT_BRCA1_1 motif binds with low affinity to the BRCT domain of BRCA1. ... BRCT_BRCA1_2 LIG_BRCT_MDC1_1 LIG_CAP-Gly_1 LIG_CSK_EPIYA_1 LIG_CSL_BTD_1 LIG_EH_1 LIG_EVH1_1 LIG_EVH1_2 LIG_EVH1_3 LIG_FHA_1 ... Dna Damage Induced Protein Phosphorylation (also annotated in these classes: LIG_BRCT_BRCA1_2 LIG_BRCT_MDC1_1 MOD_PIKK_1 ) ...
View mouse Brca1 Chr11:101488764-101551955 with: phenotypes, sequences, polymorphisms, proteins, references, function, ... IPR036420 BRCT domain superfamily. IPR011364 Breast cancer type 1 susceptibility protein (BRCA1) ... C.129-Cdkn2ctm1Yxi Brca1tm1Bhk. J:198018 View. Brca1tm1Arge/Brca1tm1Thl. Waptm1(cre)Arge/0. involves: 129S/SvEv * 129S1/Sv * ... Brca1tm1Brn/Brca1tm1Brn. Trp53tm1Brn/Trp53tm1Brn. Tg(KRT14-cre)8Brn/0. involves: 129P2/OlaHsd * BALB/cJ * FVB/N. J:126551 View ...
BRCT_assocInterPro annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, without ... Gene namesi. Name:Brca1Imported. ,p>Information which has been imported from another database using automatic procedures.,/p> , ... tr,Q9JKL6,Q9JKL6_RAT BRCA1 (Fragment) OS=Rattus norvegicus GN=Brca1 PE=2 SV=1 ... BRCA1Imported. ,p>Information which has been imported from another database using automatic procedures.,/p> ,p>,a href="/manual ...
It contains three BRCT (BRCA1-carboxyl terminal) domains. The N-terminal region directly binds with chromatin remodeling ... tandem BRCT domains) are involved in cellular DNA damage response. The MCPH1 gene associates with evolution of brain size, and ... It contains three BRCT (BRCA1-carboxyl terminal) domains. The N-terminal region directly binds with chromatin remodeling ... In this study we solve the crystal structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone as well as ...
A) Molecular feature of the mutant form of BRCA1 lacking the second BRCT domain. BRCA1/pcDNA3 was digested by ApaI to generate ... Furthermore, mutant forms of BRCA1 lacking the C-terminal second BRCA1 C-terminal (BRCT) domain showed reduced p53-mediated ... Coimmunoprecipitation of BRCA1 and p53. (A) Endogenous BRCA1 protein was immunoprecipitated by anti-BRCA1 polyclonal antibody ( ... Lanes: 1 and 5, pcDNA3 vector; 2, p53; 3 and 7, BRCA1; 4, p53 plus BRCA1; 6, E2F1 plus DP1; 8, E2F1, DP1 plus BRCA1. ...
... by preventing unscheduled expression of developmental genes (By similarity). Plays a key role in establishing the ... facilitates the association of transcription initiation factors with the promoters of the metabolism-related genes (By ... Supports the transcription of genes involved in energy metabolism in cardiomyocytes; ... Interacts with the first BRCT repeat of BRCA1 (PubMed:11739404). Interacts with KIAA1191 (PubMed:21153684). ...
... really interesting new gene; PALB2, partner and localizer of BRCA2; BRCT, BRCA1 C-terminal; OB, oligonucleotide/oligosaccharide ... To find potential targetable gene mutations we developed a 157 ovarian cancer gene panel. This panel is comprised of all genes ... Illustration of the BRCA1 and BRCA2 genes, including exons, introns, and functional domains noting location of BRCA mutations ... Prevalence of mutations in a panel of breast cancer susceptibility genes in BRCA1/2-negative patients with early-onset breast ...
The human breast and ovarian cancer type 1 susceptibility gene (BRCA1) encodes a protein of 1,863 amino acids. BRCA1 has two ... which disrupts the BRCA1 BRCT domain interaction with phosphorylated proteins and the accumulation of BRCA1 at damage-induced ... The RING domain sequence encodes a folded protein structure and confers the E3 ubiquitin ligase activity of BRCA1, and the BRCT ... Subsequently, the BRCA1 core complex (BRCA1, BRCA2 (also known as FANCD1), partner and localizer of BRCA2 (PALB2; also known as ...
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. Genes Dev. 16, 583-593 (2002). ... of the DE genes. (C) Gene set enrichment analysis of iASPP-regulated genes in KEGG pathways (475 genes) (Top) and genes up- ... S1A). Gene set enrichment analysis of these DE genes showed that iASPP-regulated genes are enriched in the canonical p53 ... A) Intersection of DE genes identified by RNA-seq and genes with differential p53 binding identified by ChIP-seq in iASPP- ...
A homologue of the breast cancer-associated gene BARD1 is involved in DNA repair in plants.. EMBO J. 25 4326-37 2006 ... It also contains a BRCT C-terminal domain, an approximately 100 amino acid tandem repeat, which appears to act as a phospho- ... The aimal BRCA1 protein is a E3 ubiquitin-protein ligase that specifically mediates the formation of Lys-6-linked ... Arabidopsis BRCA1-related proteins includes AtBRCA1(AT4G21070, Q8RXD4) and AtBARD1 (AT1G04020, F4I443). Both are involved in ...
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... "Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes & Development. 16 (5): ... Ekblad CM, Friedler A, Veprintsev D, Weinberg RL, Itzhaki LS (Mar 2004). "Comparison of BRCT domains of BRCA1 and 53BP1: a ... "Entrez Gene: TP53BP1 tumor protein p53 binding protein 1". Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der ...
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes Dev. 16 (5): 583-93. doi ... BRCA1 is a human tumor suppressor gene (also known as a caretaker gene) and is responsible for repairing DNA. BRCA1 and BRCA2 ... BRCA1 interacts with the NELF-B (COBRA1) subunit of the NELF complex. Certain variations of the BRCA1 gene lead to an increased ... BRCA1 Protein at the US National Library of Medicine Medical Subject Headings (MeSH) Genes, BRCA1 at the US National Library of ...
Complete information for CCAR2 gene (Protein Coding), Cell Cycle And Apoptosis Regulator 2, including: function, proteins, ... with BRCA1 (via the BRCT domains) (PubMed:20160719). Interacts (via N-terminus) with CHEK2 (via protein kinase domain) (PubMed: ... Evolution for CCAR2 Gene. ENSEMBL:. Gene Tree for CCAR2 (if available). TreeFam:. Gene Tree for CCAR2 (if available). Aminode: ... Gene Ontology (GO) annotations related to this gene include enzyme inhibitor activity. An important paralog of this gene is ...
All three missense mutations affect the highly conserved BRCT domain of BRCA1, but their functional relevance is unknown. ... The same strategy was applied to scan 16140 nucleotides of the BRCA1 gene (19.1% of the total gene length) comprising the 22 ... of the total gene sequence. Whereas linkage analysis indicates an 81% contribution of the BRCA1 gene to the pathogenesis of ... BRCA1 is a tumor suppressor gene spanning a region of 81 kb of genomic DNA (4) and is characterized by 22 coding exons (open ...
BARD1 is vital in the rapid relocation of BRCA1 to DNA damage sites.[13] BARD1 tandem BRCA1 C-terminus (BRCT) motifs fold into ... BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.[5][6][7] The human BARD1 ... "Entrez Gene: BARD1 BRCA1 associated RING domain 1".. *^ Fox, David; Le Trong, Isolde; Rajagopal, Ponni; Brzovic, Peter S.; ... BRCA1-A complex. • BRCA1-BARD1 complex. • ubiquitin ligase complex. • cell nucleus. • nucleoplasm. • nuclear speck. • ...
The Mayo Clinic team investigated a specific kind of protein the BRCA1 gene codes for, known as a BRCT-domain protein. The BRCT ... the BRCA1 gene can function correctly to suppress tumors. Without phosphorylation of BRCA1 binding partners, BRCA1 cannot ... These proteins are essential to the effective tumor-suppression function that BRCA1 genes perform. Biology Backgrounder Genes ... "BRCA1 tumor suppressor gene." They focused on this gene because an estimated 50 percent of inherited breast cancers are linked ...
Structure of BRCA1-BRCT/Abraxas Complex Reveals Phosphorylation-Dependent BRCT Dimerization at DNA Damage Sites. Mol Cell 61(3 ... Genes Dev.29(8):803-16, 2015.. Yang Y, Hadjikyriacou A, Xia Z, Gayatri S, Kim D, Zurita-Lopez C, Kelly R, Guo A, Li W, Clarke ... Genes Dev. 29(6):591-602, 2015.. Zhan Y, Kost-Alimova M, Shi X, Leo E, Bardenhagen JP, Shepard HE, Appikonda S, Vangamudi B, ... MLL4 Is Required to Maintain Broad H3K4me3 Peaks and Super-Enhancers at Tumor Suppressor Genes. Mol Cell. 2018 Jun 7;70(5):825- ...
Genes Dev 2015; Zeqiraj et al. Mol Cell 2015). Cancer causing BRCA1 BRCT mutants fail to interact with RAP80 and consequently ... We have demonstrated that an interaction between the BRCA1 BRCT domain and the RAP80 ubiquitin binding protein targets BRCA1 to ... Germline mutations to the Breast Cancer 1 (BRCA1) or Breast Cancer 2 (BRCA2) genes are the major cause of hereditary breast and ... Sobhian B, Shao G, Lilli DR, Culhane AC, Moreau LA, Xia B, Livingston DM*, Greenberg RA*: RAP80 targets BRCA1 to specific ...
They identified Swift (Smad wing for transcriptional activation), a protein containing six BRCA1 COOH-terminal (BRCT) domains. ... K. Shimizu, P.-Y. Bourillot, S. J. Nielsen, A. M. Zorn, J. B. Gurdon, Swift is a novel BRCT domain coactivator of Smad2 in ... Swiftly Increasing TGF-β-Mediated Gene Expression Message Subject. (Your Name) has forwarded a page to you from Science ... Swift bound to Smad2 in vitro and in vivo, and the association of these two proteins required the three BRCT domains located ...
Mutation of Brca1 gene increases the phosphorylation and the kinase activity of AKT. The BRCA1-BRCT domains bind to ... WT, wild-type Brca1 plasmid; Mu, Brca1-BRCT mutant (M1775R, point mutation in BRCT domains). D, BRCA1 affects FOXO3a activity ... D, BRCA1-BRCT domains interact with pAKT. Lysates were incubated with GST-BRCA1-BRCT wild-type and M1775R and P1749R mutant ... Most BRCA1 mutations cause truncated BRCA1 gene products that lack one or both COOH-terminal BRCT domains. Clinically relevant ...
BRCT domains are homologous to the COOH-terminal region of the breast cancer susceptibility gene BRCA1 and are thought to ... Callebaut I., Mornon J. P. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair.. FEBS Lett., 400: ... DNA Repair Gene XRCC1 Polymorphisms, Smoking, and Bladder Cancer Risk. Mariana C. Stern, David M. Umbach, Carla H. van Gils, ... DNA Repair Gene XRCC1 Polymorphisms, Smoking, and Bladder Cancer Risk. Mariana C. Stern, David M. Umbach, Carla H. van Gils, ...
"Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure". Genes Dev. 16 (5): 583-93. doi ... "BRCA1 gene tree". Ensembl.. *^ Duncan JA, Reeves JR, Cooke TG (October 1998). "BRCA1 and BRCA2 proteins: roles in health and ... Gene locationEdit. The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair ... BRCT domainsEdit. The dual repeat BRCT domain of the BRCA1 protein is an elongated structure approximately 70 Å long and 30-35 ...
Complex rearrangement in BRCA1 results in the in-frame loss of exons in the BRCT domain. Am J Hum Genet1999;65:A1792. ... Color bar coding the BRCA1 gene on combed DNA: a useful strategy for detecting large gene rearrangements. Genes Chrom Cancer ... TheBRCA1 Exon 13 Duplication Screening Group 2000. The exon 13 duplication in the BRCA1 gene is a founder mutation present in ... In the BRCA1 gene, a number of different Alu mediated rearrangements, ranging from 510 bp to 23.8 kb, have been found to date.2 ...
Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure». Genes Dev. 16 (5): 583-93. PMC ... O gene BRCA1 apresenta penetrância incompleta. No caso do câncer de mama as mutações no gene BRCA1 apresentam uma penetrância ... Mutações encontradas no gene do BRCA1[editar , editar código-fonte]. Espectro de mutações deletérias em BRCA1 (n=57) e BRCA2 (n ... BRCA1 (em inglês, breast cancer 1, early onset) é um gene humano pertencente a classe dos genes supressores de tumor conservado ...
  • The BRCA1 BRCT domain binds pSer-x-x-Phe motifs in partner proteins to regulate the cellular response to DNA damage. (rcsb.org)
  • DNA damage-induced ubiquitylation by RING finger proteins 8 (RNF8) and 168 (RNF168) is also required for both 53BP1 and BRCA1 recruitment 14 , but these signalling pathways are not cell-cycle specific 14 . (nature.com)
  • BRCT domains are present in proteins that are associated with DNA damage response. (eu.org)
  • The RING domain sequence encodes a folded protein structure and confers the E3 ubiquitin ligase activity of BRCA1, and the BRCT domains bind phosphorylated proteins that are primarily involved in the DNA damage response. (nih.gov)
  • The sites at which other BRCA1-interacting proteins bind are also shown. (nih.gov)
  • Important clinical mutations routinely used in research settings are indicated, such as Cys61Gly and Cys64Gly, which target the RING domains, and Met1775Arg, which disrupts the BRCA1 BRCT domain interaction with phosphorylated proteins and the accumulation of BRCA1 at damage-induced foci. (nih.gov)
  • This entry includes animal BRCA1 (BREAST CANCER SUSCEPTIBILITY 1) proteins and their homologues from plants [ PMID: 22629260 ]. (ebi.ac.uk)
  • Arabidopsis BRCA1-related proteins includes AtBRCA1(AT4G21070, Q8RXD4 ) and AtBARD1 (AT1G04020, F4I443 ). (ebi.ac.uk)
  • 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 , and developmentally important genes such as the polycomb group of genes. (wikipedia.org)
  • 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. (wikipedia.org)
  • [13] Double stranded breaks (DSB) in DNA trigger poly(ADPribose) polymerase 1 (PARP1) to catalyze the formation of poly(ADPribose) (PAR) so that PAR can then bind to an array of DNA response proteins, including the BRCA1/BARD1 heterodimer, and target them to DNA damage sites. (wikipedia.org)
  • BRCA1 and BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. (wikipedia.org)
  • Our work has revealed a partial molecular understanding for how BRCA1 recognizes DNA damage and competes with opposing DNA repair proteins to control genome integrity. (upenn.edu)
  • Swift bound to Smad2 in vitro and in vivo, and the association of these two proteins required the three BRCT domains located nearest the Swift COOH-terminus. (sciencemag.org)
  • Glutathione S -transferase (GST) fusion BRCA1 proteins were produced in Escherichia coli and purified according to the manufacturer's instructions (Amersham Pharmacia Biotech). (aacrjournals.org)
  • In the language of science, their principal finding is this: That a specific biochemical modification known as "phosphorylation" (fos-for-a-LAY-shun) is required at certain cell-cycle stages to activate proteins associated with the BRCA1 gene. (innovations-report.com)
  • These proteins are essential to the effective tumor-suppression function that BRCA1 genes perform. (innovations-report.com)
  • BRCT domains are found in many proteins involved in cell-cycle regulation, and have for some years been thought to be key players in cell-cycle regulation. (innovations-report.com)
  • Understanding the interactions between BRCT domains and their targets will help researchers make the next move: to devise drug interventions that exploit phosphorylation bonds between key proteins. (innovations-report.com)
  • 000114857 520__ $$aComputer analysis of a conserved domain, BRCT, first described at the carboxyl terminus of the breast cancer protein BRCA1, a p53 binding protein (53BP1), and the yeast cell cycle checkpoint protein RAD9 revealed a large superfamily of domains that occur predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. (epfl.ch)
  • The BRCT domain consists of approximately 95 amino acid residues and occurs as a tandem repeat at the carboxyl terminus of numerous proteins, but has been observed also as a tandem repeat at the amino terminus or as a single copy. (epfl.ch)
  • The retinoblastoma protein (a universal tumor suppressor) and related proteins may contain a distant relative of the BRCT domain. (epfl.ch)
  • BRCA1 is a multifunctional protein that binds dozens of other proteins, the most important of which is BARD1 [ 9 - 11 ] (see Figure 1(a) ). (hindawi.com)
  • Once translated in the cytoplasm, BRCA1 can move to the centrosome where it dimerizes with BARD1 to ubiquitinate proteins such as gamma-tubulin that regulate centrosome duplication and microtubule nucleation, or to the mitochondria where it is implicated in cell survival and/or apoptosis regulation. (hindawi.com)
  • 53BP1 contains two breast cancer susceptibility gene 1 COOH terminus (BRCT) motifs, which are present in several proteins involved in DNA repair and/or DNA damage-signaling pathways. (rupress.org)
  • Both BRCA1 and BRCA2 proteins play a crucial role in the maintenance of genomic integrity through the process of precise DNA repair by homologous recombination [ 7 ], [ 8 ]. (jcancer.org)
  • TopBP1 ( top oisomerase IIβ b inding p rotein) contains eight BR CA1 c arboxyl- t erminal (BRCT) motifs, which are found in proteins involved in DNA repair and cell cycle checkpoints. (asm.org)
  • To determine potential binding partners of BRCA1 that might elucidate its role in DNA repair, we immunoprecipitated 35 S-methionine-labeled T24 human bladder carcinoma cells with BRCA1 antibodies, and three coprecipitated cellular proteins (150, 95, and 84 kD) were revealed ( 6 ). (sciencemag.org)
  • The BRCT domain is a protein binding site typically found on DNA repair proteins like BRCA1 that are responsible for maintaining genomic stability and facilitating DNA repair. (vcu.edu)
  • BASC is a protein complex that in part binds to the BRCT domain and serves as a "docking site" for other proteins and enzymes to come in, effectively repair the DNA damage and leave when repair is completed. (vcu.edu)
  • Localization of BRCA1 is regulated by interactions with other proteins such as the BRCA1-associated RING domain protein 1 (BARD1) [ 19 , 20 ]. (mdpi.com)
  • Therefore, proteins containing BRCT domains are important for DNA damage detection and signaling. (usf.edu)
  • In this dissertation, we focus on two BRCT-containing proteins BRCA1 and PAXIP1. (usf.edu)
  • To further analyze the function of BRCT-containing proteins, a study was previously undertaken to evaluate the role of BRCT-containing proteins and their interaction partners in the DNA damage response and consequently, cancer. (usf.edu)
  • BRCT domains of seven BRCT-containing proteins were used as baits and their binding partners were demonstrated to be highly enriched in the DDR process. (usf.edu)
  • Therefore, we probed this established dataset containing the protein-protein interaction network (PPIN) of seven BRCT-containing proteins to identify seventeen kinases. (usf.edu)
  • Overall, these studies indicate that BRCT-containing proteins through their role in the DDR and the cell cycle are crucial for both cancer prevention and therapy. (usf.edu)
  • The hereditary breast and ovarian cancer gene, BRCA1, encodes a large polypeptide that contains the cysteine-rich RING motif, a zinc-binding domain found in a variety of regulatory proteins. (nih.gov)
  • The manner by which the two BRCT repeats interact in BRCA1 may represent a general mode of interaction between homologous domains within proteins that interact to regulate the cellular response to DNA damage. (nih.gov)
  • The BRCA1 breast cancer gene contains a tandem pair of BRCT domains that function together a unit to bind to specific phosphorylated proteins involved in detection and repair of DNA damage. (mit.edu)
  • BRCA1 gene mutations may produce truncated proteins that lose the ability to interact with associated proteins. (foxchase.org)
  • Cells that contain dysfunctional BRCA1 proteins are hypersensitive to DNA damaging agents. (foxchase.org)
  • We are examining the ability of mutant BRCA1 proteins to contribute to homologous recombination in both cancer cell line models and genetically engineered mouse models. (foxchase.org)
  • Bona fide Fanconi anemia proteins, BRCA2 (FANCD1), PALB2 (FANCN), and BRIP1 (FANCJ), interact with BRCA1 during ICL repair. (aacrjournals.org)
  • To complicate matters, histone H2A is actually a large class of different proteins mined from different genes. (extremetech.com)
  • We report here that mus101 encodes a member of the BRCT (BRCA1 C terminus) domain superfamily of proteins implicated in DNA repair and cell cycle checkpoint control. (genetics.org)
  • There are 72534 BRCT domains in 52588 proteins in SMART's nrdb database. (embl-heidelberg.de)
  • Taxonomic distribution of proteins containing BRCT domain. (embl-heidelberg.de)
  • The complete taxonomic breakdown of all proteins with BRCT domain is also avaliable . (embl-heidelberg.de)
  • Click on the protein counts, or double click on taxonomic names to display all proteins containing BRCT domain in the selected taxonomic class. (embl-heidelberg.de)
  • The second BRCT domain of BRCA1 proteins interacts with p53 and stimulates transcription from the p21WAF1/CIP1 promoter. (embl-heidelberg.de)
  • These results demonstrate for the first time the presence of a second p53 interaction domain in BRCA1 proteins and suggests that BRCA1a and BRCA1b proteins, like BRCA1, function as p53 co-activators. (embl-heidelberg.de)
  • These results suggest that one of the mechanisms by which BRCA1 proteins function is through recruitment of CBP/p300 associated HAT/FAT activity for acetylation of p53 to specific promoters resulting in transcriptional activation. (embl-heidelberg.de)
  • Percentage points are related to the number of proteins with BRCT domain which could be assigned to a KEGG orthologous group, and not all proteins containing BRCT domain. (embl-heidelberg.de)
  • The results obtained showed that this mutation prevents the interaction of BRCA1 with key proteins of the cell cycle, subsequently impairing BRCA1-dependent induction of cell cycle arrest. (openaccesspub.org)
  • The BRCT domain mediates binding with phosphorylated proteins such as: Abraxas 3 , 4 , BACH1/BRIP1 5 , and CtlP 6 , forming three mutually exclusive protein complexes named A, B and C complexes (see below). (openaccesspub.org)
  • A number of other proteins also bind to the C-terminal region of BRCA1 and/or its central region 7 ( Figure 1 ). (openaccesspub.org)
  • BRCA1 domains and interacting proteins: BRCA1 contains a RING domain at its N-terminus, two BRCT domains at the C-terminus and a coiled-coil domain upstream of BRCT domains. (openaccesspub.org)
  • What is the Tissue in which BRCA1 is the most expressed, with which proteins does it interact? (bios-project.eu)
  • BACKGROUND/AIM: Numerous missense mutations have been determined in the BRCT domain of the BRCA1 gene, affecting localization and interaction of BRCA1 with other proteins. (bvsalud.org)
  • The identification and characterization of large and structurally complex genes involved in cancer predisposition, such as the breast and ovarian cancer predisposing genes BRCA1 and BRCA2 (1 , 2) , have stimulated efforts aimed at improving mutation detection in large DNA regions to enable the recognition of high-risk individuals. (aacrjournals.org)
  • If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. (wikipedia.org)
  • Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics. (wikipedia.org)
  • citation needed] BRCA1 is unrelated to BRCA2, i.e. they are not homologs or paralogs. (wikipedia.org)
  • BRCA1 polypeptides, in particular, Lys-48-linked polyubiquitin chains are dispersed throughout the resting cell nucleus, but at the start of DNA replication, they gather in restrained groups that also contain BRCA2 and BARD1. (wikipedia.org)
  • As a focal point to interrogate these interrelationships, we are devoted to the elucidation of BRCA1- and BRCA2- dependent homologous recombination DNA repair mechanisms and their roles in breast and ovarian cancer susceptibility. (upenn.edu)
  • Germline mutations to the Breast Cancer 1 (BRCA1) or Breast Cancer 2 (BRCA2) genes are the major cause of hereditary breast and ovarian cancer susceptibility. (upenn.edu)
  • Clinical BRCA1 and BRCA2 mutations render cells deficient in error-free mechanisms of DNA repair known as homologous recombination, implicating these activities in tumor suppression and response to genotoxic therapies. (upenn.edu)
  • [11] [12] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation , damaged DNA is not repaired properly, and this increases the risk for breast cancer . (wikipedia.org)
  • We tested German families with a strong history of breast and ovarian cancer for mutations in the BRCA1 and BRCA2 genes by direct sequencing and DHPLC. (bmj.com)
  • In order to assess the possibility that the families, previously tested negative for both BRCA1 and BRCA2 coding region mutations (153 families) and for BRCA -UV (47 families), could carry large DNA rearrangements in the BRCA1 gene, we screened them (total 200) for known founder mutations IVS21-36del510 and ins6kbEx13 by a mutation specific PCR based assay. (bmj.com)
  • The association of breast cancer susceptibility genes BRCA1 and BRCA2 with breast and ovarian cancer development was first demonstrated over 20 years ago. (jcancer.org)
  • In this review we discuss the biological functions of BRCA1 and BRCA2 genes and the role of BRCA mutations in tumor initiation, regulation of cancer stemness, therapy resistance and tumor progression. (jcancer.org)
  • Mutations in the tumor suppressor genes BRCA1 (breast cancer susceptibility gene 1) and BRCA2 (breast cancer susceptibility gene 2) predispose to different types of cancer. (jcancer.org)
  • Since then specific germline mutations in BRCA1 and BRCA2 genes were linked to increased risk of several additional types of human malignancies including prostate, colorectal, stomach and pancreatic cancers [ 3 ]-[ 5 ]. (jcancer.org)
  • Mutations in BRCA1 and BRCA2 genes are associated with about 20% of familial breast and ovarian cancers [ 4 ], [ 6 ]. (jcancer.org)
  • In contrast to the gynecological tumors, the reported contribution of BRCA1 and BRCA2 mutations to the hereditary of pancreatic, stomach and prostate cancer is marginal [ 3 ]-[ 5 ]. (jcancer.org)
  • Há também o domínio chamado Coiled Coil em BRCA1, por meio do qual este interage com BRCA2 por intermédio da proteínas PALB2 (partner and localizer of BRCA2) durante o reparo por recombinação homólogo. (wikipedia.org)
  • Espectro de mutações deletérias em BRCA1 (n=57) e BRCA2 (n=56) em mulheres jovens com câncer de mama unilateral (em amarelo) e contralateral (em vermelho). (wikipedia.org)
  • Nessa população foi encontrado duas mutações associadas ao gene BRCA1 , uma deleção dos nucleotídeos AG na posição 185 e uma inserção de uma C na posição 5382, e uma mutação associada ao gene BRCA2 . (wikipedia.org)
  • Hassan AIT Benhassou, Nadia Bouchoutrouch, Youssef Amar, Hassan Sefrioui (2014) Hereditary Breast Cancer in Moroccan Populations: BRCA1 & BRCA2 at the Glance. (omicsonline.org)
  • The aim of the present communication is to discuss the established relationship between the mutations occurring both in BRCA1 & BRCA2 genes and the inherited breast cancer in female Moroccan patients and to summarize most of the relevant Moroccan studies that have been performed in this field. (omicsonline.org)
  • Germline inactivating mutations in BRCA1 and BRCA2 genes are responsible for Hereditary Breast and Ovarian Cancer Syndrome (HBOCS). (plos.org)
  • Mutations in BRCA1 and BRCA2 genes confer high lifetime risks of breast and ovarian cancer, among other neoplasias [2] , [3] . (plos.org)
  • Thus, genetic analysis of BRCA1 and BRCA2 is a cornerstone of genetic counseling practice. (plos.org)
  • However, classification of genetic variants as pathogenic is challenging, particularly for missense changes and for silent or intronic variants that cannot be directly associated with increased cancer risk and are classified as variants of uncertain significance (VUS), which are found in 13% of BRCA1 and BRCA2 genetic tests [5] . (plos.org)
  • Diverse multifactorial likelihood algorithms have been developed and applied for both BRCA1 and BRCA2 variants (reviewed in Spurdle et al. (plos.org)
  • Therefore, functional analyses that assess specific properties of BRCA1 or BRCA2 may help to classify VUS [7] . (plos.org)
  • Identification of candidate cancer predisposing variants by performing whole-exome sequencing on index patients from BRCA1 and BRCA2-negative breast cancer families. (cancerindex.org)
  • Mutation of BRCA1 and BRCA2 is the most common cause of inherited breast and ovarian cancer. (bmj.com)
  • Functional assays provide an important alternative for classification of BRCA1 and BRCA2 VUS. (bmj.com)
  • 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. (bmj.com)
  • While functional assays have been developed to independently evaluate BRCA1 and BRCA2 VUS, high-throughput assays with sufficient sensitivity to characterise the large number of identified variants are lacking. (bmj.com)
  • Additionally, because of relatively low conservation of certain domains of BRCA1, and of BRCA2, between humans and rodents, heterologous expression in rodent cells may have limited reliability or capacity to assess variants present throughout either protein. (bmj.com)
  • In the 1990s, pathogenic variants in BRCA1 and BRCA2 were found to be associated with hereditary breast and ovarian cancer (HBOC). (bmj.com)
  • 1 2 Among genes associated with HBOC, BRCA1 and BRCA2 confer the highest lifetime risks of these cancers and are the most frequently mutated genes in women with HBOC. (bmj.com)
  • 3-6 Other cancers also show elevated incidence of mutations in BRCA1 (melanoma and testicular) and BRCA2 (male breast cancer, prostate cancer and pancreatic cancer). (bmj.com)
  • Genetic testing for pathogenic variants in BRCA1 , BRCA2 and other cancer susceptibility genes is recommended for individuals with a strong family and/or personal history of HBOC (see figure 1 ), since risk preventative strategies improve outcomes. (bmj.com)
  • Indeed, individuals who carry a pathogenic variant in BRCA1 and BRCA2 are recommended to consider prophylactic surgeries including bilateral risk-reducing mastectomy (RRM) and/or risk-reducing bilateral salpingo-oophorectomy (rrBSO). (bmj.com)
  • ICL recognition by the canonical ubiquitinated D2-I complex is thought to direct subsequent DNA replication-dependent processing of ICLs in S-phase to DNA double-strand break (DSB) intermediates that require BRCA1 and BRCA2 for homology-directed DNA repair ( 5, 6 ). (aacrjournals.org)
  • Mutations in the BRCA1 and BRCA2 genes constitute a risk factor for breast cancer development. (springer.com)
  • We intend to provide an overview of the current state of BRCA1 and BRCA2 mutation description and classification. (springer.com)
  • Capalbo C, Ricevuto E, Vestri A et al (2006) BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models. (springer.com)
  • Giannini G, Capalbo C, Ristori E et al (2006) Novel BRCA1 and BRCA2 germline mutations and assessment of mutation spectrum and prevalence in Italian breast and/or ovarian cancer families. (springer.com)
  • Eccles DM, Mitchell G, Monteiro ANA et al (2015) BRCA1 and BRCA2 genetic testing-pitfalls and recommendations for managing variants of uncertain clinical significance. (springer.com)
  • Lincoln SE, Yang S, Cline MS et al (2017) Consistency of BRCA1 and BRCA2 variant classifications among clinical diagnostic laboratories. (springer.com)
  • Chenevix-Trench G, Milne RL, Antoniou AC et al (2007) An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). (springer.com)
  • Spurdle AB, Healey S, Devereau A et al (2012) ENIGMA-evidence-based network for the interpretation of germline mutant alleles: an international initiative to evaluate risk and clinical significance associated with sequence variation in BRCA1 and BRCA2 genes. (springer.com)
  • In a candidate gene study aiming at identifying genetic determinants of breast cancer susceptibility, we undertook the full sequencing of the NBN gene in our cohort of 97 high-risk non-BRCA1 and -BRCA2 breast cancer families, along with 74 healthy unrelated controls, also from the French Canadian population. (cdc.gov)
  • A and Pro919Ser on familial BC risk by means of TaqMan allelic discrimination, analysing BRCA1/BRCA2 mutation-negative index patients of 571 German BC families and 712 control individuals. (springer.com)
  • median 45) without deleterious BRCA1 and BRCA2 mutations. (springer.com)
  • All women gave written consent to the molecular analysis of the BRCA1 and BRCA2 genes and potential new breast cancer susceptibility genes. (springer.com)
  • Mutations in the open reading frame of BRCA1 and BRCA2 were excluded by applying denaturing high performance liquid chromatography (DHPLC) on all exons, followed by direct sequencing of conspicuous exons. (springer.com)
  • Deleterious variants in the BRCA1 and BRCA2 genes account for approximately 20% of cases of hereditary breast and ovarian cancer. (openaccesspub.org)
  • BRCA1 and BRCA2 gene alterations are found in the majority of these cases. (bvsalud.org)
  • New therapies are needed to reduce recurrence in patients with BRCA1 or BRCA2 germline mutation-associated early breast cancer. (bvsalud.org)
  • METHODS: We conducted a phase 3, double-blind, randomized trial involving patients with human epidermal growth factor receptor 2 (HER2)-negative early breast cancer with BRCA1 or BRCA2 germline pathogenic or likely pathogenic variants and high-risk clinicopathological factors who had received local treatment and neoadjuvant or adjuvant chemotherapy. (bvsalud.org)
  • BACKGROUND: Women with pathogenic BRCA1 and BRCA2 mutations possess a high risk of developing breast and ovarian cancer. (bvsalud.org)
  • [7] [8] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation , damaged DNA is not repaired properly, and this increases the risk for breast cancer . (allbiomed.org)
  • Inherited mutations in the breast cancer susceptibility genes BRCA1 and BRCA2 are associated with a markedly increased risk of breast and ovarian cancer. (scienceintheclassroom.org)
  • Mutations in BRCA1 are present in 45% of families that segregate with susceptibility for breast cancer and in 80-90% of families with both breast and ovarian cancer. (nih.gov)
  • The breast and ovarian cancer type 1 susceptibility protein (BRCA1) has pivotal roles in the maintenance of genome stability. (nih.gov)
  • The human breast and ovarian cancer type 1 susceptibility gene ( BRCA1 ) encodes a protein of 1,863 amino acids. (nih.gov)
  • A model for targeting the breast and ovarian cancer type 1 susceptibility protein (BRCA1) to damage-induced foci at DNA double-stranded breaks that involves a ubiquitin-dependent signal transduction pathway. (nih.gov)
  • Seven breast/ovarian cancer families with high probability of BRCA1-related predisposition were screened. (aacrjournals.org)
  • [8] Three missense mutations , each affecting BARD1's BRCT domain, are known to be implicated in cancers: C645R is associated with breast and ovarian cancers, V695L is associated with breast cancer, and S761N is associated with breast and uterine cancers. (wikipedia.org)
  • The breast and ovarian cancer susceptibility gene BRCA1 contains an unusually high density (41.5%) of Alu elements. (bmj.com)
  • Thus, this is the first report of large rearrangements in the BRCA1 gene in German breast and ovarian cancer families. (bmj.com)
  • All families investigated participate in a study of the "German Consortium for Hereditary Breast and Ovarian Cancer" to establish a BRCA1 / 2 mutation profile and to determine family types with high frequencies of particular mutations. (bmj.com)
  • Inherited mutations in the BRCA1 gene predispose to a higher risk of breast/ovarian cancer. (hindawi.com)
  • in healthy cells it functions to maintain proper genomic repair and cell division, but inherited mutations in the BRCA1 gene encode altered forms of the protein that contribute to development of breast and ovarian cancer [ 2 - 4 ]. (hindawi.com)
  • While the BARD1 gene, also regarded as a tumor suppressor, is susceptible to germ-line and somatic mutations, these occur at a much lower frequency in a subset of breast/ovarian cancers [ 12 - 14 ]. (hindawi.com)
  • Mutations or alterations that affect the BRCA1 gene are linked to familial breast and ovarian cancer syndromes. (news-medical.net)
  • BRCA1 encodes a tumor suppressor that is mutated in familial breast and ovarian cancers. (sciencemag.org)
  • BRCA1 is a tumor-suppressor gene linked to familial breast and ovarian cancers ( 1 ). (sciencemag.org)
  • It is widely known that mutations in the breast cancer susceptibility 1 (BRCA1) gene significantly increase the chance of developing breast and ovarian cancers, but the mechanisms at play are not fully understood. (vcu.edu)
  • Recently published in the journal Aging, the study led by Kristoffer Valerie, Ph.D., discovered that certain BRCA1 mutations affecting the BRCA1 C-terminal (BRCT) binding site resulted in excessive DNA repair, or hyper-recombination, which may contribute to the development of breast and ovarian cancers. (vcu.edu)
  • Our findings suggest that caution should be exercised when targeting BRCA1 for breast and ovarian cancer therapies," says Valerie, co-leader of the Radiation Biology and Oncology program and a professor in the Department of Radiation Oncology at VCU Massey Cancer Center. (vcu.edu)
  • Mutations of BRCA1 are found in a high percentage of hereditary breast and ovarian cancers [ 1 ]. (mdpi.com)
  • BRCA1 is a gene that is known to be associated with increased risk of hereditary breast and ovarian cancer. (usf.edu)
  • Germline variants of BRCA1 are assessed to determine lifetime risk of developing breast and ovarian cancer. (usf.edu)
  • Evaluation of the functional impact of germline BRCA1 variants that are likely to be associated to breast and ovarian cancer could help to investigate the mechanism of BRCA1 tumorigenesis. (unboundmedicine.com)
  • Mutations in breast cancer susceptibility gene BRCA1 (breast cancer early-onset 1) are associated with increased risk of developing breast and ovarian cancers. (sigmaaldrich.com)
  • The breast cancer susceptibility gene, BRCA1 , is mutated in a high percentage of hereditary breast and ovarian cancers. (biomedcentral.com)
  • Eighty percent of women who inherit mutant forms of the BRCA1 protein develop breast cancer and 65% develop ovarian cancer. (mit.edu)
  • The BRCA1 gene is commonly mutated in hereditary breast and ovarian cancers. (foxchase.org)
  • Inherited mutations in the breast and ovarian cancer susceptibility gene BRCA1 are associated with high risk for developing breast and ovarian cancers. (embl-heidelberg.de)
  • In Spain, families that carry the deleterious mutation in the BRCA1 gene have a 52% cumulative risk of developing breast cancer and a 22% risk of developing ovarian cancer by the age of 70 1 . (openaccesspub.org)
  • The aim of this study was to analyse the BRCA1 gene in the ovarian cancer risk group to characterize the spectrum of its mutations in the Czech Republic. (bvsalud.org)
  • Mutations in this gene are responsible for approximately 40% of inherited breast cancers and more than 80% of inherited breast and ovarian cancers. (origene.com)
  • Germline mutations of the breast cancer 1 (BRCA1) gene are a major cause of familial breast and ovarian cancer. (scienceintheclassroom.org)
  • BRCA1 (breast and ovarian cancer susceptibility protein 1) is a RING finger protein containing a BRCT domain. (acris-antibodies.com)
  • Inherited loss of BRCA1 function confers an increased susceptibility for both breast and ovarian cancer. (acris-antibodies.com)
  • Screening of BRCA1 mutation using immunohistochemical staining with C-terminal and N-terminal antibodies in familial ovarian cancers. (acris-antibodies.com)
  • Familial Breast/Ovarian Cancer and BRCA1/2 Genetic Screening: The Role of Immunohistochemistry as an Additional Method in the Selection of Patients. (acris-antibodies.com)
  • Reduced BRCA1 gene expression is common in the sporadic form of ovarian carcinoma. (aacrjournals.org)
  • Therefore, a microenvironmental change that is manifested during the initial stages of ovarian carcinoma dissemination may, potentially, help suppress BRCA1 expression in sporadic tumors and thus promote their progression. (aacrjournals.org)
  • Given BRCA1′s myriad roles in acting to maintain genomic stability and differentiation, determining how its expression is silenced during the development of high-grade ovarian tumors is an important goal. (aacrjournals.org)
  • In mice carrying a breast cancer-derived mutation in the BRCA1 C-terminal (BRCT) domain, we find that ATM becomes essential for supporting the residual levels of HDR necessary to repair a DNA break. (pnas.org)
  • To investigate this question, we used the Brca1 S1598F mouse model carrying a mutation in the BRCA1 C-terminal domain of BRCA1. (pnas.org)
  • Structural consequences of a cancer-causing BRCA1-BRCT missense mutation. (rcsb.org)
  • The IlE26Ala mutation abrogates the BRCA1 E3 ubiquitin ligase activity and is predicted to maintain the RING structure. (nih.gov)
  • The aim of this study was to develop a protocol for reliable, sensitive, and cost-effective mutation scanning of the BRCA1 gene, based on a modification of fluorescence-assisted mismatch analysis. (aacrjournals.org)
  • Mutation of Brca1 gene increases the phosphorylation and the kinase activity of AKT. (aacrjournals.org)
  • Formation of irradiation-induced foci positive for BRCA1, hRad50, hMre11, or p95 was dramatically reduced in HCC/1937 breast cancer cells carrying a homozygous mutation in BRCA1 but was restored by transfection of wild-type BRCA1 . (sciencemag.org)
  • BRCA mutation research has been an active field since the discovery of the genes, and new mutations in both genes are constantly described and classified according to several systems. (springer.com)
  • G (p.Pro1812Ala) in the BRCA1 gene (detected in a patient from a high risk family) and also to mechanistically understand the effect of this mutation in DNA damage response, a key process in cancer development. (openaccesspub.org)
  • Learning more about the functions of these genes could help us develop prophylactic strategies to reduce this risk in BRCA mutation carriers-as well as better chemotherapeutics to treat tumors that harbor BRCA mutations. (scienceintheclassroom.org)
  • In contrast, a mutation that ablates phosphoprotein recognition by the BRCA C terminus (BRCT) domains of BRCA1 elicits tumors in each of the three GEM models. (scienceintheclassroom.org)
  • High-grade serous subtype tumors are also notable because they also have the highest rate of BRCA1 abnormalities, a considerable proportion of which occur due to epigenetic silencing rather than mutation ( 2 ). (aacrjournals.org)
  • BARD1 ankyrin repeat domain mutations disabling H4K20me0 recognition abrogate accumulation of BRCA1 at DSBs, causing aberrant build-up of 53BP1, and allowing anti-resection activity to prevail in S and G2. (nature.com)
  • Collectively, this reveals that BRCA1-BARD1 monitors the replicative state of the genome to oppose 53BP1 function, routing only DSBs within sister chromatids to HR. (nature.com)
  • BRCA1 exists as a stable heterodimer through its RING-mediated interaction with BRCA1-associated RING domain protein 1 (BARD1), which is inhibited by BRCA1-associated protein 1 (BAP1). (nih.gov)
  • A homologue of the breast cancer-associated gene BARD1 is involved in DNA repair in plants. (ebi.ac.uk)
  • BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene . (wikipedia.org)
  • Most, if not all, BRCA1 heterodimerizes with BARD1 in vivo . (wikipedia.org)
  • [9] BARD1 and BRCA1 form a heterodimer via their N-terminal RING finger domains . (wikipedia.org)
  • The BARD1-BRCA1 interaction is observed in vivo and in vitro and is essential for BRCA1 stability. (wikipedia.org)
  • BARD1 shares homology with the two most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. (wikipedia.org)
  • [8] BARD1 expression is upregulated by genotoxic stress and involved in apoptosis through binding and stabilizing p53 independently of BRCA1. (wikipedia.org)
  • BARD1 is vital in the rapid relocation of BRCA1 to DNA damage sites. (wikipedia.org)
  • [13] BARD1 tandem BRCA1 C-terminus (BRCT) motifs fold into a binding pocket with a key lysine residue (K619), and bind to poly(ADP-ribose) (PAR), which targets the BRCA1/BARD1 heterodimer to damaged DNA sites. (wikipedia.org)
  • [14] When the BRCA1/BARD1 heterodimer is transported to the damaged DNA site, it acts as an E3 ubiquitin ligase . (wikipedia.org)
  • [9] The BRCA1/BARD1 heterodimer ubiquitinates RNA polymerase II, preventing the transcription of the damaged DNA, and restoring genetic stability. (wikipedia.org)
  • Inhibiting cancer cells' BRCA1/BARD1 heterodimer from relocating to DNA damage sites would induce tumor cell death rather than repair. (wikipedia.org)
  • One inhibition possibility is the BARD1 BRCT key lysine residue (K619). (wikipedia.org)
  • Inhibiting this lysine residue's ability to bind poly(ADP-ribose) would prevent the BRCA1/BARD1 heterodimer from localizing to DNA damage sites and subsequently prevent DNA damage repair. (wikipedia.org)
  • These four helices combine to form a heterodimerization interface and stabilize the BRCA1-BARD1 heterodimer complex. (wikipedia.org)
  • BRCA1 nuclear transport and ubiquitin E3 ligase enzymatic activity are tightly regulated by the BRCA1 dimeric binding partner BARD1 and further modulated by cancer mutations and diverse signaling pathways. (hindawi.com)
  • BARD1 forms a stable heterodimer with BRCA1, stimulating its nuclear localization and ubiquitin E3 ligase activity. (hindawi.com)
  • a) Protein domain structure of BRCA1 showing the location of nuclear localization signals (NLSs), nuclear export signals (NESs), and binding sites for BARD1 and gamma-tubulin. (hindawi.com)
  • In response to DNA damage, BRCA1 is sequestered (as a dimer with BARD1) to different types of DNA repair complexes at foci. (hindawi.com)
  • The interaction with BARD1 tends to trap BRCA1 in the nucleus through the masking of its NES. (hindawi.com)
  • If BRCA1 is not bound to BARD1, it is exported to the cytoplasm by the CRM1 export receptor, and this has been linked to the roles of BRCA1 in apoptosis and in centrosome duplication as revealed by functional comparison of wild-type and NES-mutated forms of BRCA1. (hindawi.com)
  • We now show that these autoantibodies are directed against BARD1, originally identified as a protein interacting with the product of the breast cancer gene 1, BRCA1 . (aacrjournals.org)
  • Moreover, we show that the cleavage site of BARD1 is located NH2 terminally but downstream of the RING domain essential for BARD1 and BRCA1 protein interaction. (aacrjournals.org)
  • This BRCA1-associated RING domain (BARD1) protein contains an N-terminal RING motif, three tandem ankyrin repeats, and a C-terminal sequence with significant homology to the phylogenetically conserved BRCT domains that lie near the C terminus of BRCA1. (nih.gov)
  • The BARD1/BRCA1 interaction is disrupted by BRCA1 missense mutations that segregate with breast cancer susceptibility, indicating that BARD1 may be involved in mediating tumour suppression by BRCA1. (nih.gov)
  • The RING domain is located at the amino terminus of BRCA1, between amino acids 1 and 109 (exons 2 - 7), and it is responsible for the E3·ubiquitin·ligase activity of BRCA1 2 and binds to the BARD1 protein. (openaccesspub.org)
  • The BRCA1-BARD1 heterodimer specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. (abcam.com)
  • The homodimer is more susceptible to proteolytic cleavage than the BARD1/BRCA1 heterodimer. (abcam.com)
  • BRCA1 interacts with BRCA1-associated RING domain protein 1 (BARD1) to form a potent E3 ligase (5, 6) that is thought to regulate multiple pathways, including those responsible for tumor suppression ( 1 - 4 ). (scienceintheclassroom.org)
  • The BRCA1 protein has been reported to interact with RNA polymerase II holoenzyme and BARD1. (acris-antibodies.com)
  • Here we report that BRCA1 stimulates artificial and genomic promoter constructs containing p53-responsive elements. (nih.gov)
  • BRCA1 stimulates genomic promoters containing p53-responsive elements. (nih.gov)
  • BRCA1 is a tumor suppressor gene spanning a region of 81 kb of genomic DNA (4) and is characterized by 22 coding exons (open reading frame, 5592 nucleotides) including exon 11, which represents 61.3% of the coding sequence (3426 nucleotides). (aacrjournals.org)
  • BRCA1 has been implicated in DNA damage repair, cell cycle checkpoint control, transcriptional regulation, and maintenance of genomic stability, which are key factors in tumorigenesis ( 1 , 2 ). (aacrjournals.org)
  • Both AKT and BRCA1 regulate the cell cycle and genomic stability through the CHK1 pathway ( 2 , 13 ), and BRCA1 regulates estrogen receptor-α activity in a phosphoinositide 3-kinase/AKT-dependent manner ( 14 ), strongly supporting the notion that the AKT pathway contributes to BRCA1-mediated tumorigenesis. (aacrjournals.org)
  • Ectopic homologous recombination, such as that reported in the BRCA1 gene, leads to large genomic rearrangements, which subsequently may cause disease phenotypes. (bmj.com)
  • The primary tumor suppressing role of BRCA1 relates to the maintenance of genomic integrity through regulation of DNA replication, repair, and transcription, in addition to various cell cycle checkpoints that ensure survival of healthy cells [ 6 ]. (hindawi.com)
  • Since then the germline mutations within these genes were linked to genomic instability and increased risk of many other cancer types. (jcancer.org)
  • The p53 tumor suppressor gene serves as a checkpoint in maintaining genomic stability ( 19 ), and p53 function is impaired in the majority of human cancers. (asm.org)
  • Subsequently, the BRCA1 gene was cloned and analyzed to be composed of 22 coding exons distributed over ~100 kb of genomic DNA [ 4 , 5 ]. (mdpi.com)
  • The BRCA1 gene is conserved in mammals [ 21 , 22 ] and the BRCA1 protein has roles in various cellular events including cell cycle control, DNA damage signaling, maintaining genomic integrity, protein ubiquitination, and transcriptional regulation. (mdpi.com)
  • Sequence analysis of genomic DNA from ILV1 revertant clones showed that BRCA1-induced ilv1-92 reversion by base substitution when GR is at least 6-fold over the control. (unboundmedicine.com)
  • Our results suggest that both 53BP1 and SRC3 have a common function that converge at the BRCA1 promoter and possibly other genes important for DNA repair and genomic stability. (biomedcentral.com)
  • Five overlapping fragments amplified on both genomic DNA and cDNA were used to screen for the whole protein-coding sequence of the BRCA1 gene. (bvsalud.org)
  • This gene encodes a nuclear phosphoprotein that plays a role in maintaining genomic stability, and it also acts as a tumor suppressor. (origene.com)
  • These results suggest that, besides its role in maintaining genomic stability, BRCA1 directly regulates the expression of angiogenic factors to modulate the tumor microenvironment. (ncku.edu.tw)
  • Additionally, fluorescence polarization assays demonstrate that MCPH1 tandem BRCT domains show a binding selectivity on pSer +3 and prefer to bind phosphopeptide with free COOH-terminus. (rcsb.org)
  • The BRCA1 protein contains the following domains: Zinc finger, C3HC4 type (RING finger) BRCA1 C Terminus (BRCT) domain This protein also contains nuclear localization signals and nuclear export signal motifs. (wikipedia.org)
  • Clinically relevant missense mutations identified at the COOH terminus of BRCA1 abolish the BRCT structure ( 1 , 2 ), and Brca1 deficiency leads to tumor formation in mice ( 5 ). (aacrjournals.org)
  • The BRCA1 protein is also called RING finger protein 53 and has two known domains - Zinc finger, C3HC4 type (RING finger) and BRCA1 C Terminus (BRCT) domain. (news-medical.net)
  • Viral gene products target residues of the N terminus of p53 that are employed to interact with the transcriptional machinery of cells ( 20 ). (asm.org)
  • BRCA1 is a large protein of 1863 residues with two small structured domains at its termini: a RING domain at the N-terminus and a BRCT (BRCA1 C-terminus domain) repeat domain at the C-terminus. (sigmaaldrich.com)
  • It is likely that both protein context (location of the BRCT domains at the C-terminus of the large BRCA1 protein) and cellular environment (binding partners, molecular chaperones) buffer these destabilizing effects such that at least some mutant protein is able to adopt the folded functional state. (sigmaaldrich.com)
  • Here, we show that the Xenopus BRCA1 COOH terminus repeat-containing Xmus101 protein is required for loading of Cdc45 onto the origin. (rupress.org)
  • The breast cancer susceptibility gene contains at its C terminus two copies of a conserved domain that was named BRCT for BRCA1 C terminus. (embl-heidelberg.de)
  • An unusual feature of paired BRCT motifs is that the phosphopeptides bind across the domain-domain interface ( Clapperton,2004 ). (eu.org)
  • Many of the BRCT ligands are likely to be at pSQ motifs phosphorylated by the checkpoint kinases, ATM, ATR, DNA-PK ( Glover,2004 ). (eu.org)
  • BRCA1-binding motifs are S..F.K (high affinity) or S..F (lower affinity) ( Clapperton,2004 ). (eu.org)
  • Since consensus motifs have so far been defined for just a few BRCT domains, the range of different binding motif patterns could be quite large. (eu.org)
  • BRCA1 has two highly conserved motifs at its termini: the RING domain and tandem BRCT domains. (nih.gov)
  • The RAP80 ubiquitin interaction motifs (UIMs) provide an ubiquitin recognition element to target the BRCA1 E3 ligase and a K63-ubiquitin specific deubiquitinating enzyme BRCC36 to DNA double strand breaks. (upenn.edu)
  • The BRCA1 BRCT domains are phospho-protein binding motifs that are important for the tumor suppressor function of BRCA1 ( 4 - 6 ). (aacrjournals.org)
  • The protein encoded by this gene contains an N-terminal forkhead domain, two BRCA1 C-terminal (BRCT) motifs and a central domain with 13 repetitions of an approximately 41-amino acid sequence. (fishersci.com)
  • This nuclear protein interacts with phosphorylated histone H2AX near sites of DNA double-strand breaks through its BRCT motifs, and facilitates recruitment of the ATM kinase and meiotic recombination 11 protein complex to DNA damage foci. (fishersci.com)
  • Breast cancer type 1 susceptibility protein (BRCA1) promotes HR by antagonizing the anti-resection factor TP53-binding protein 1(53BP1) (refs. (nature.com)
  • However, H4K20me1/2 dilution cannot explain 53BP1 suppression and the shift to HR, as breast cancer type 1 susceptibility protein (BRCA1) is required to antagonize 53BP1 accumulation at DSBs in S/G2 (refs. (nature.com)
  • Phosphorylation of S239 in the BRCT-binding motif of ATR-interacting protein (ATRIP) induces binding to the Breast cancer type 1 susceptibility protein (BRCA1) protein. (eu.org)
  • Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene. (wikipedia.org)
  • Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 ( / ˌ b r æ k ə ˈ w ʌ n / ) gene . (wikipedia.org)
  • The LIG_BRCT_BRCA1_1 motif binds with low affinity to the BRCT domain of BRCA1. (eu.org)
  • The N-terminal region directly binds with chromatin remodeling complex SWI-SNF, and the C-terminal BRCT2-BRCT3 domains (tandem BRCT domains) are involved in cellular DNA damage response. (rcsb.org)
  • The BRCT-domain influences how the protein binds and with what protein partners it binds -- which in turn, affects the role the protein plays in the cycle of cell growth. (innovations-report.com)
  • The BRCT domain binds to the central domain of p53 which is required for sequence specific DNA binding. (embl-heidelberg.de)
  • This BRCT domain also binds in vitro to CBP. (embl-heidelberg.de)
  • Mouse B2 RNA binds Pol II and inhibits transcription of protein-coding genes during heat shock [ 17 , 18 ]. (portlandpress.com)
  • In Escherichia coli , 6 S RNA binds RNA polymerase and inhibits transcription of housekeeping genes upon entry of stationary cell growth [ 19 - 21 ]. (portlandpress.com)
  • Inactivating germline mutations in these genes account for 20-50% of familial cases, depending on the population [4] . (plos.org)
  • Patients with germline BRCA1/2 mutations should be educated regarding additional personal cancer risk, and risk for family members. (bvsalud.org)
  • Guidelines recommend that all men with metastatic prostate cancer should also undergo somatic tissue and germline testing for priority genes BRCA1/2, PALB2, ATM, and MSH2/6. (bvsalud.org)
  • ATM-mediated HDR is not affected by the status of 53BP1, an antagonizing factor of BRCA1. (pnas.org)
  • BRCA1 is essential for homology-directed repair (HDR) of DNA double-strand breaks in part through antagonism of the nonhomologous end-joining factor 53BP1. (pnas.org)
  • Whereas both ATM and BRCA1 promote end resection, which can be regulated by 53BP1, 53bp1 deletion does not rescue the HDR defects of Atm mutant cells, in contrast to Brca1 mutant cells. (pnas.org)
  • These results demonstrate that ATM has a role in HDR independent of the BRCA1-53BP1 antagonism and that its HDR function can become critical in certain contexts. (pnas.org)
  • Tumor suppressor p53-binding protein 1 also known as p53-binding protein 1 or 53BP1 is a protein that in humans is encoded by the TP53BP1 gene. (wikipedia.org)
  • In particular, BRCA1 and 53BP1 play a role in determining the balance between the two pathways. (wikipedia.org)
  • We have also gained an understanding of how chromatin environment affects DNA repair mechanism choice (i.e. whether a break is repaired by homologous recombination or nonhomologous end-joining), which revealed a basis for competition between BRCA1 and 53BP1, and responses to DNA damaging therapies such as PARP inhibitors (Tang et al. (upenn.edu)
  • However using chromatin immunoprecipitation(ChIP) and siRNA knockdown, we have demonstrated that both SRC3 and 53BP1 co-occupy the same region of the BRCA1 promoter and both are required for BRCA1 expression in HeLa cells. (biomedcentral.com)
  • Previous studies emphasized the importance of the BRCT domain, which shows homology with p53 binding protein (53BP1), in transcriptional activation, growth inhibition and tumor suppression. (embl-heidelberg.de)
  • Comprehensive analysis of missense variations in the BRCT domain of BRCA1 by structural and functional assays. (rcsb.org)
  • Structure and mechanism of BRCA1 BRCT domain recognition of phosphorylated BACH1 with implications for cancer. (rcsb.org)
  • Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. (rcsb.org)
  • This phospho-protein mediated interaction of the BRCT domain has a central role in cell-cycle check point and DNA repair functions. (eu.org)
  • The BRCT domain: signaling with friends? (eu.org)
  • The BRCT domain is a phospho-protein binding domain. (eu.org)
  • Furthermore, mutant forms of BRCA1 lacking the C-terminal second BRCA1 C-terminal (BRCT) domain showed reduced p53-mediated transcriptional activation. (nih.gov)
  • It also contains a BRCT C-terminal domain, an approximately 100 amino acid tandem repeat, which appears to act as a phospho-protein binding domain [ PMID: 14576433 ]. (ebi.ac.uk)
  • The three missense mutations affect the highly conserved BRCT domain. (aacrjournals.org)
  • The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. (wikipedia.org)
  • the Znf C3HC4- RING domain, the BRCA1 serine domain and two BRCT domains. (wikipedia.org)
  • We have demonstrated that an interaction between the BRCA1 BRCT domain and the RAP80 ubiquitin binding protein targets BRCA1 to K63-linked ubiquitin structures present at DNA damage sites. (upenn.edu)
  • K. Shimizu, P.-Y. Bourillot, S. J. Nielsen, A. M. Zorn, J. B. Gurdon, Swift is a novel BRCT domain coactivator of Smad2 in transforming growth factor-β signaling. (sciencemag.org)
  • The Mayo Clinic team investigated a specific kind of protein the BRCA1 gene codes for, known as a BRCT-domain protein. (innovations-report.com)
  • The Mayo team showed that phosphorylation of a binding partner is necessary to activate the BRCT-domain protein. (innovations-report.com)
  • Once activated, the BRCT-domain protein then helps regulate vital tasks in the cell cycle. (innovations-report.com)
  • RING, serine containing domain (SCD), and BRCT domains are indicated. (wikipedia.org)
  • Another previously described domain that is shared by bacterial NAD-dependent DNA-ligases, the large subunits of eukaryotic replication factor C, and poly(ADP-ribose) polymerases appears to be a distinct version of the BRCT domain. (epfl.ch)
  • Thus, the BRCT domain is likely to perform critical, yet uncharacterized, functions in the cell cycle control of organisms from bacteria to humans. (epfl.ch)
  • The carboxyterminal BRCT domain of BRCA1 corresponds precisely to the recently identified minimal transcription activation domain of this protein, indicating one such function. (epfl.ch)
  • BRCA1 domain structure and subcellular transport pathways. (hindawi.com)
  • The regulation is mediated by an interaction between the seventh and eighth BRCT domains of TopBP1 and the DNA-binding domain of p53, leading to inhibition of p53 promoter binding activity. (asm.org)
  • The hallmarks of BRCA1 protein include an NH 2 -terminal RING finger domain and BRCA1 COOH-terminal (BRCT) repeats that mediate binding to CtIP ( 2 ). (sciencemag.org)
  • When DNA damage occurs, various forms of BASC (BRCA1-associated genome surveillance complex) bind to the BRCT domain on BRCA1. (vcu.edu)
  • The BRCA1 protein contains an N -terminal really interesting new gene (RING) finger domain and two BRCA1 C -Terminal (BRCT) domains, which are involved in various protein-protein interactions [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. (mdpi.com)
  • The BRCA1 protein also has a DNA-binding domain [ 13 , 14 ] and an SQ-cluster domain (SCD) in its central region [ 15 ]. (mdpi.com)
  • Our group pioneered the use of functional assays to analyze mutations in the BRCA1 BRCT domain, and have developed computation models to predict their functional impact in the BRCA genes. (moffitt.org)
  • Several functional assays have been conducted to evaluate VUS in BRCA1 at the level of its global and domain-based functions, including ubiquitin ligase activity assays, protease sensitivity assays, phosphopeptide binding assays, small colony phenotype assays, yeast localization phenotype assays, and embryonic stem cell-based functional assays (review in Millot et al. (plos.org)
  • In the work presented here, we combine a functional assay - the transcription activation (TA) assay, which is based on the function of the BRCA1 carboxy-terminal region (aa 1396-1863) in transcriptional activation domain when linked to a sequence-specific DNA binding module - [10] with protein structural analyses [11] to assess the functional impact of seven BRCA1 C-terminal VUS. (plos.org)
  • rad51∆ strain, the pathogenic variants C61G and A1708E induced a weak but significant increase in GR. On the other hand, in rad50∆ mutant expressing the pathogenic variants localised at the BRCT domain, a further GR increase was seen. (unboundmedicine.com)
  • 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. (cancerindex.org)
  • Here we determine the crystal structure of the BRCT domain of human BRCA1 at 2.5 A resolution. (nih.gov)
  • The domain contains two BRCT repeats that adopt similar structures and are packed together in a head-to-tail arrangement. (nih.gov)
  • Prior to our studies only two domains had been identified - the N-terminal RING domain and the C-terminal BRCT domain - and while the structures of both these domains provide a platform from which the structural consequences of missense mutations can be predicted, they only account for 16% of the total protein and hundreds of mutations of unknown pathogenicity remain to be characterised. (biomedcentral.com)
  • Mutations occur most frequently in the N-terminal RING, exons 11-13, or the BRCA C-terminal (BRCT) domain. (foxchase.org)
  • Additionally, mutations in the BRCT domain of BRCA1 create protein-folding defects that result in protease-mediated degradation. (foxchase.org)
  • As the authors show, when this particular molecule uses its own BRCT domain to recognize its partner, they fit together like a hand and glove. (extremetech.com)
  • The BRCT domain is not limited to the C-terminal of protein sequences and can be found in multiple copies or in a single copy as in RAP1 and TdT. (embl-heidelberg.de)
  • Some data [( PUBMED:9799248 )] indicate that the BRCT domain functions as a protein-protein interaction module. (embl-heidelberg.de)
  • In addition, the C-terminal second BRCA1 (BRCT) domain is sufficient for p53 mediated transactivation of the p21 promoter. (embl-heidelberg.de)
  • The p53 interaction domain of BRCA1a/1b maps, in vitro, to the second BRCT domain (aa 1760-1863). (embl-heidelberg.de)
  • SwissProt sequences and OMIM curated human diseases associated with missense mutations within the BRCT domain. (embl-heidelberg.de)
  • G (p.Pro1812Ala) BRCA1, cause loss of BRCT domain activity. (openaccesspub.org)
  • The two most important domains of BRCA1 are the RING domain and the BRCT domain. (openaccesspub.org)
  • The authors developed Bractoppin, a drug-like inhibitor of phosphopeptide recognition by the human BRCA1 tandem BRCA1 C-terminal (BRCT) domain, which selectively inhibits substrate binding with nanomolar potency in vitro . (mammarycellnews.com)
  • The deletion of exons 21 and 22 affects the BRCT functional domain of the BRCA1 protein. (bvsalud.org)
  • MATERIALS AND METHODS: We examined whether the M1775K and V1809F mutations in the BRCT domain affect BRCA1 cellular localization. (bvsalud.org)
  • BRCA1 exerts transcriptional repression through interaction with CtIP in the C-terminal BRCT domain and ZBRK1 in the central domain. (ncku.edu.tw)
  • However, how ATM genetically interacts with BRCA1 in this process is unclear. (pnas.org)
  • The ATM kinase is involved in various aspects of DNA damage signaling and repair, but how ATM participates in HDR and genetically interacts with BRCA1 in this process is unclear. (pnas.org)
  • Here, it is shown that BRCA1 interacts in vitro and in vivo with hRad50, which forms a complex with hMre11 and p95/nibrin. (sciencemag.org)
  • BRCA1 interacts with hRad50 in vivo and in vitro. (sciencemag.org)
  • This gene encodes a protein which interacts with the N-terminal region of BRCA1. (cancerindex.org)
  • Here we describe a novel protein that interacts in vivo with the N-terminal region of BRCA1. (nih.gov)
  • It is localized predominantly in the nucleus and interacts with CTBP, with the C-terminal (BRCT) domains of BRCA1, and with the retinoblastoma protein. (emdmillipore.com)
  • In spite of extensive efforts studying BRCA1 and AKT individually, an interaction of BRCA1 and AKT has not been reported. (aacrjournals.org)
  • The BRCA1 tumor suppressor is a 1863 amino acid protein with multiple protein interaction domains that facilitate its roles in regulating DNA repair and maintenance, cell cycle progression, transcription, and cell survival/apoptosis. (hindawi.com)
  • The RING and BRCT protein interaction domains are shown at the amino and carboxy termini, respectively. (hindawi.com)
  • We combine detailed literature curation, large scale yeast two-hybrid screening and tandem-affinity purification coupled to mass spectrometry to generate an annotated protein-protein interaction network mediated by all BRCT domains in the human proteome. (moffitt.org)
  • We hypothesized that members of this BRCT-centric protein-protein interaction network could constitute targets for sensitization to DNA damaging chemotherapy agents in lung cancer. (usf.edu)
  • Since BRCA1 and BACH1 mutations targeting the BRCA1-BACH1 interaction have been associated with breast cancer susceptibility, the results of the present study thus provide evidence for a novel role of BACH1 in tumour suppression. (antikoerper-online.de)
  • Yeast screens identify the RNA polymerase II CTD and SPT5 as relevanttargets of BRCA1 interaction. (embl.de)
  • Such phenotypic similarity implies direct physical association and/or functional interaction between respective gene products. (springer.com)
  • hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. (ebi.ac.uk)
  • Without phosphorylation of BRCA1 binding partners, BRCA1 cannot function to suppress tumors. (innovations-report.com)
  • BRCA1 forms a complex with RBBP8 and MRN (MRE11/RAD50/NBN) in a cell cycle-dependent manner during S and G2 phase of the cell cycle through the BRCT domains of BRCA1 binding to phosphorylated S327, a CDK phosphorylation site of RBBP8 in a phospho-SPxF motif. (genenames.org)
  • Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. (abnova.com)
  • The BRCA1 protein displays E3 ubiquitin ligase activity, and this enzymatic function is thought to be required for tumor suppression. (scienceintheclassroom.org)
  • BRCA1 acts as a tumor suppressor and can function as a secreted growth inhibitory protein, participate in transcription coupled repair of oxidative DNA damage, X-chromosome inactivation, and can function as a E3 ubiquitin ligase. (acris-antibodies.com)
  • BRCT repeats as phosphopeptide-binding modules involved in protein targeting. (eu.org)
  • Interactions between BRCT repeats and phosphoproteins: tangled up in two. (eu.org)
  • BRCA1 mutant cells lacking the BRCT repeats accumulate nuclear pAKT and consequently inactivate the transcription functions of FOXO3a, a main nuclear target of pAKT. (aacrjournals.org)
  • They focused on this gene because an estimated 50 percent of inherited breast cancers are linked to growth errors -- also called mutations -- in this gene. (innovations-report.com)
  • Finally, we consider its significance in prevention and/or treatment of BRCA1-related cancers. (mdpi.com)
  • Investigators identified single aldehyde dehydrogenase positive cells with a hybrid epithelial/mesenchymal phenotype that express genes associated with aggressive triple-negative breast cancers. (mammarycellnews.com)
  • Finally, developing yeast-based assays to characterise BRCA1 missense variants could be useful to design more precise therapies. (unboundmedicine.com)
  • The identification of functional domains in BRCA1 will therefore be critical to the development of functional assays to evaluate their pathogenicity. (biomedcentral.com)
  • The tumor suppressors BRCA1 and ATM have both been implicated in the early steps of homologous recombination, also termed homology-directed repair (HDR). (pnas.org)
  • Expression of pathogenic BRCA1 missense variants increased homologous recombination (HR) and gene reversion (GR) in yeast. (unboundmedicine.com)
  • 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)
  • A host of reports implicate a role for BRCA1 in the repair of damaged DNA, in particular that of double-strand breaks by homologous recombination. (biomedcentral.com)
  • They identified Swift (Smad wing for transcriptional activation), a protein containing six BRCA1 COOH-terminal (BRCT) domains. (sciencemag.org)
  • Under these conditions, steady state levels of BRCA1 mRNA and protein fell significantly and the transcriptional activation state of the BRCA1 promoter was suppressed. (aacrjournals.org)
  • Inherited mutations in cancer susceptibility genes play a causal role in 5-10% of newly diagnosed tumours. (bvsalud.org)
  • Approximately 120 distinct missense variants have been identified in the BRCA1 BRCT through breast cancer screening, and several of these have been linked to an increased cancer risk. (rcsb.org)
  • Here we probe the structures and peptide-binding activities of variants that affect the BRCA1 BRCT phosphopeptide-binding groove. (rcsb.org)
  • We focus on the role of BRCA1 in cancer and integrate statistical, structural, and functional data to aid in clinical annotation of hundreds of variants found in the population. (moffitt.org)
  • 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). (usf.edu)
  • We have a developed a visualization resource to aid in functional analysis of BRCA1 missense variants that occur due to single amino acid changes. (usf.edu)
  • This tool is known as BRCA1 Circos (http://research.nhgri.nih.gov/bic/circos/) and it aggregates, harmonizes and allows interpretation of data from all published studies on functional analysis of BRCA1 missense variants. (usf.edu)
  • Functional studies of BRCA1 also demonstrate that majority of the variants that have a functional impact on the protein lie in the BRCT region of the protein. (usf.edu)
  • Genetic testing of these genes is available, although approximately 15% of tests identify variants of uncertain significance (VUS). (plos.org)
  • Structural analysis of the three variants located in the BRCT domains (Y1703S, W1718L and G1770V) reveals significant alterations of BRCT structure. (plos.org)
  • The TA assay shows that variants Y1703S, W1718L and G1770V dramatically compromise the transcriptional activity of BRCA1, while variants Q1409L, S1473P, E1586G and R1589H behave like wild-type BRCA1. (plos.org)
  • In conclusion, our results suggest that variants Y1703S, W1718L and G1770V can be classified as likely pathogenic BRCA1 mutations. (plos.org)
  • Thus, BRCA1 missense variants require specific genetic functions and presumably induced GR by different mechanisms. (unboundmedicine.com)
  • As DNA repair is regulated by cell cycle, we determined the effect on GR of BRCA1 variants in cell cycle-arrested RSYwt cells. (unboundmedicine.com)
  • TY - JOUR T1 - Effect of BRCA1 missense variants on gene reversion in DNA double-strand break repair mutants and cell cycle-arrested cells of Saccharomyces cerevisiae. (unboundmedicine.com)
  • Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. (cancerindex.org)
  • As an initial step toward determining which ESEs predicted by the web-based tool ESEfinder in the breast cancer susceptibility gene BRCA1 are likely to be functional, we have determined their evolutionary conservation and compared their location with known BRCA1 sequence variants. (biomedcentral.com)
  • This is the first report on the prediction of the frequency and distribution of ESEs in the BRCA1 gene, and it is the first reported attempt to predict which ESEs are most likely to be functional and therefore which sequence variants in ESEs are most likely to be pathogenic. (biomedcentral.com)
  • Studies of the pathogenicity of nucleotide sequence variants in disease-associated genes usually focus on the effect on encoded protein structure and function. (biomedcentral.com)
  • BRCA1 splice variants BRCA1a (p110) and BRCA1b (p100) associates with CBP/p300 co-activators. (embl-heidelberg.de)
  • Many alternatively spliced transcript variants, some of which are disease-associated mutations, have been described for this gene, but the full-length natures of only some of these variants has been described. (origene.com)
  • In addition, recent proteomic and genetic studies have revealed the presence of distinct BRCA1 complexes in vivo, each of which governs a specific cellular response to DNA damage. (nih.gov)
  • The BRCA1 gene is a genetic sequence that is located on the long arm of chromosome 17 at the 17q21 position. (news-medical.net)
  • Our study demonstrated that BRCA1 may interfere with yeast DNA repair functions that are active in S-phase causing high level of GR. In addition, we confirmed here that yeast could be a reliable model to investigate the mechanism and genetic requirements of BRCA1-induced genome instability. (unboundmedicine.com)
  • Further genetic analysis revealed that mus101 is an essential gene. (rupress.org)
  • Genetic control of these cell‐cycle delays was first demonstrated when the RAD9 gene was shown to be required for the G 2 /M arrest after irradiation with X‐rays ( Weinert and Hartwell, 1988 ). (embopress.org)
  • Genetic analysis has resulted in the identification of several genes in addition to RAD9 that are required for all DNA damage checkpoints. (embopress.org)
  • So far, seven genetic loci (MCPH1-7) for this condition have been mapped with seven corresponding genes ( MCPH1 , WDR62 , CDK5RAP2 , CEP152 , ASPM , CENPJ , and STIL ) identified from different world populations. (biomedcentral.com)
  • BRCA1 inactivating mutations lead to genetic instability, indirectly causing tumours to occur as a result of an accumulation of mutations in cell cycle regulatory genes. (openaccesspub.org)
  • ATM loss is associated with synthetic lethality of BRCT mutant mice, which provides insight into the therapeutic potential of utilizing ATM kinase inhibitors in combination with PARP-inhibitor therapy for certain BRCA1-deficient tumors. (pnas.org)
  • When these tasks are accomplished, the BRCA1 gene can function correctly to suppress tumors. (innovations-report.com)
  • Overexpression of TopBP1 to a level comparable to that seen in breast tumors leads to inhibition of p53 target gene expression and DNA damage-induced apoptosis and G 1 arrest. (asm.org)
  • Consistently, Brca1-deficient mouse mammary tumors exhibit accelerated growth, pronounced vascularization, and overexpressed ANG1. (ncku.edu.tw)
  • The aimal BRCA1 protein is a E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage [ PMID: 10500182 , PMID: 10724175 ]. (ebi.ac.uk)
  • This paper will focus on the transport, dynamics, and multiple intracellular destinations of BRCA1 with emphasis on how regulation of these events has impact on, and determines, a broad range of important cellular functions. (hindawi.com)
  • BRCA1 gene mutations disrupt these processes and result in chromosome instability and defective checkpoints that accelerate cellular transformation [ 6 - 8 ]. (hindawi.com)
  • The gene helps in deoxyribonucleic acid (DNA) repair and keeps cellular proliferation in check. (news-medical.net)
  • These data suggest that BRCA1 is important for the cellular responses to DNA damage that are mediated by the hRad50-hMre11-p95 complex. (sciencemag.org)
  • Second, we seek to understand how BRCT domains convey signals during the cellular response to DNA Damage. (moffitt.org)
  • In the PPIN, WEE1 was shown to interact with PAXIP1 (PTIP), a BRCT-containing protein involved in transcription and in the cellular response to DNA damage. (usf.edu)
  • However, the lack of detailed phenotypic and cellular characterization of a patient with biallelic BRCA1 mutations has precluded assignment of BRCA1 as a definitive Fanconi anemia susceptibility gene. (aacrjournals.org)
  • By and large, primary microcephaly patients are phenotypically indistinguishable, however, recent studies in patients with mutations in MCPH1, WDR62 and ASPM genes showed a broader clinical and/or cellular phenotype. (biomedcentral.com)
  • Ataxia-telangiectasia (A-T) and Nijmegen breakage syndrome (NBS) are well-known single-gene disorders, which have similar cellular phenotypes, including chromosome instability, radioresistant DNA synthesis, and hypersensitivity to radiation. (springer.com)
  • PDZ) and extra-cellular signalling ( e.g. integrin-binding RGD), control of gene expression ( e.g. (rsc.org)
  • A recently discovered mechanism for gene regulation involves non-coding RNAs that bind and inhibit cellular RNA polymerases. (portlandpress.com)
  • Among the human genome, p53 is one of the first tumor suppressor genes to be discovered. (ijbs.com)
  • The breast cancer susceptibility gene 1 ( Brca1 ) has been shown to play a key role in both hereditary and sporadic mammary tumorigenesis ( 1 - 3 ). (aacrjournals.org)
  • BRCA1 and its toolbox for the maintenance of genome integrity. (nih.gov)
  • Thus, BRCA1 is emerging as the master regulator of the genome through its ability to execute and coordinate various aspects of the DNA damage response. (nih.gov)
  • 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)
  • BRCA1 orthologs have been identified in most vertebrates for which complete genome data are available. (wikipedia.org)
  • Gorodetska I, Kozeretska I, Dubrovska A. BRCA Genes: The Role in Genome Stability, Cancer Stemness and Therapy Resistance. (jcancer.org)
  • This is a large protein complex known of as the BRCA1-associated genome surveillance complex (BASC). (news-medical.net)
  • The breast cancer susceptibility gene 1 (BRCA1) has been well established as a tumor suppressor and functions primarily by maintaining genome integrity. (mdpi.com)
  • We thought to exploit yeast genetics to shed light on BRCA1-induced genome instability and tumorigenesis. (unboundmedicine.com)
  • Human CENPC genome location and CENPC gene details page in the UCSC Genome Browser . (wikidoc.org)
  • Our findings identify a new scrambled gene in the micronuclear genome of a spirotrichous ciliate, and suggest that even more complicated structures may be present. (labome.org)
  • Nijmegen breakage syndrome gene, NBS1, and molecular links to factors for genome stability. (springer.com)
  • BRCA1 regulates p53-dependent gene expression. (nih.gov)
  • mutants with truncated BRCA1 protein survive, have a kinky tail, pigmentation anomalies, male infertility and increased tumor incidence. (jax.org)
  • Cancer causing BRCA1 BRCT mutants fail to interact with RAP80 and consequently demonstrate inefficient recruitment to DNA damage sites. (upenn.edu)
  • However, certain BRCT mutants unable to bind to BASC disrupt the delicate DNA repair process. (vcu.edu)
  • Valerie and his colleagues showed through experiments with cultured breast cancer cells and tissue samples from breast cancer patients that BRCT mutants increased ubiquination of BASC, which, in turn, increased recombination several-fold over normal levels. (vcu.edu)
  • In the present study, we ask whether and how reduced thermodynamic stability of the isolated BRCT mutants translates into loss of function of the full-length protein in the cell. (sigmaaldrich.com)
  • To identify the mosthighly conserved of the many BRCA1 functions, we screened theevolutionarily distant eukaryote Saccharomyces cerevisiae for mutants thatsuppressed the G1 checkpoint arrest and lethality induced followingheterologous BRCA1 expression. (embl.de)
  • However, several lines of evidence suggest a role for BRCA1 in the regulation of AKT. (aacrjournals.org)
  • The Mayo Clinic research reveals the details of a molecular mechanism involved in cell cycle regulation of a gene known as the "BRCA1 tumor suppressor gene. (innovations-report.com)
  • These genes encode an Srb/mediator component, a CTD kinase, a CTD phosphatase, and a protein involved in the regulation of transcription by chromatin structure, respectively. (genetics.org)
  • Thus, it is essential to understand the function of BRCA1 in oxidative stress regulation. (mdpi.com)
  • In this review, we briefly summarize BRCA1's many binding partners and mechanisms, and discuss data supporting the function of BRCA1 in oxidative stress regulation. (mdpi.com)
  • It also participates in the quantitative and qualitative regulation of gene expression in a variety of biological processes through the selection of single or alternative poly(A) signals in transcription units. (pubmedcentralcanada.ca)
  • The C-terminal BRCT region of BRCA1 is essential for its DNA repair, transcriptional regulation and tumor suppressor functions. (nih.gov)
  • Several studies link BRCA1 to transcriptional regulation, DNA repair, apoptosis and growth/tumor suppression. (embl-heidelberg.de)
  • A, which may affect gene regulation, and Pro919Ser, on a large German familial BC study cohort. (springer.com)
  • BRCT domains were first identified in and named after the breast cancer susceptibility protein BRCA1 ( Zhang,1999 ). (eu.org)
  • Homologs of breast cancer genes in plants. (ebi.ac.uk)
  • Characterization of Arabidopsis thaliana ortholog of the human breast cancer susceptibility gene 1: AtBRCA1, strongly induced by gamma rays. (ebi.ac.uk)
  • The predominant allele has a normal, tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer. (wikipedia.org)
  • The first evidence for the existence of a gene encoding a DNA repair enzyme involved in breast cancer susceptibility was provided by Mary-Claire King's laboratory at UC Berkeley in 1990. (wikipedia.org)
  • The breast cancer susceptibility gene 1 ( BRCA1 ) plays a key role in mammary tumorigenesis. (aacrjournals.org)
  • With this breast cancer gene, the understanding is that if this gene is mutated it may trigger additional mutations throughout your lifetime and that contributes to a lifetime risk of developing breast cancer. (innovations-report.com)
  • 2- 13 Two of them, a 510 bp deletion of exon 22 (IVS21-36del510) and a 3835 bp deletion of exon 13 (IVS12-1643del3835), are founder mutations in Dutch breast cancer patients and represent 36% of all BRCA1 mutations in this population. (bmj.com)
  • In fact, the families described here with a rearrangement in the BRCA1 gene are in the most severe categories with respect to their family history (B19, group A1 and BN8, group B). Up to now the deletion IVS21-36del510 comprising exon 22 has exclusively been detected in Dutch breast cancer patients. (bmj.com)
  • Misregulation and reduced expression of BRCA1 also contribute to sporadic forms of breast cancer [ 5 ]. (hindawi.com)
  • BRCA1 (em inglês, breast cancer 1, early onset ) é um gene humano pertencente a classe dos genes supressores de tumor conservado nos mamíferos é responsável pela síntese da proteína de mesmo nome BRCA1. (wikipedia.org)
  • Regiões de aglomerados de mutações associadas ao câncer de mama (BCCRs - breast cancer cluster regions) foram encontradas para três regiões de BRCA1 (de acordo com a posição nucleotídica): c.179-c.505, c.4328-c.4945 e c.5261-c.5563. (wikipedia.org)
  • Now, researchers at Virginia Commonwealth University Massey Cancer Center have shown that certain BRCA1 mutations result in excessive, uncontrolled DNA repair, which challenges the prior assumption that mutations in BRCA1 only contribute to breast cancer through a reduction in function. (vcu.edu)
  • By disrupting ubiquitination we may be able to prevent hyper-recombination and stop the growth of cancer cells with these BRCT mutations. (vcu.edu)
  • This might sensitize the cancer cells to radiation therapy while having little effect on cells with normal BRCA1 function. (vcu.edu)
  • The researchers hope to continue studying the role of BRCA1 in DNA double-strand break repair in order to determine whether the mutations they examined are important for the onset of cancer and whether targeted therapies can be developed. (vcu.edu)
  • In the early 1990s, chromosome 17q21 was assigned to contain the locale of a gene responsible for inherited susceptibility to breast cancer in families with early-onset disease [ 2 , 3 ]. (mdpi.com)
  • DNA repair genes PAXIP1 and TP53BP1 expression is associated with breast cancer prognosis. (moffitt.org)
  • This indicates that the BRCT region is important in cancer development. (usf.edu)
  • Sturdy A, Naseem R, Webb M: Purification and characterisation of a soluble N-terminal fragment of the breast cancer susceptibility protein BRCA1. (biomedcentral.com)
  • A new mechanism for the breast cancer gene BRCA1. (mit.edu)
  • However, disruption of the tandem BRCT domains of BRCA1 that our lab has identified may allow tumor cells to be more susceptible to anti-cancer drugs. (mit.edu)
  • Here, we report the presence of biallelic BRCA1 mutations in a woman with multiple congenital anomalies consistent with a Fanconi anemia-like disorder and breast cancer at age 23. (aacrjournals.org)
  • From data from 20 triple-negative breast cancer patients, our approaches effectively prioritize genes that are essential for breast cancer cell fitness and predict patient survival, including those implicating convergent evolution. (biomedcentral.com)
  • Luciferase reporter gene assay of the promoter construct bearing this variant did not suggest a variation of expression in the MCF-7 breast cancer cell line, but indicated a reduction of luciferase expression in both the HEK293 and LNCaP cell lines. (cdc.gov)
  • Inactivating and truncating mutations of the nuclear BRCA1-interacting protein 1 (BRIP1) have been shown to be the major cause of Fanconi anaemia and, due to subsequent alterations of BRCA1 function, predispose to breast cancer (BC). (springer.com)
  • BRCA1 has been implicated in numerous DNA repair pathways that maintaingenome integrity, however the function responsible for its tumorsuppressor activity in breast cancer remains obscure. (embl.de)
  • Magnetic nanoparticles and lipid-based gene transfection methods were performed to provide active Fas expression in breast cancer cells. (mammarycellnews.com)
  • CONCLUSION: There is a correlation between subcellular localization of BRCA1 and diminished DNA repair observed in breast cancer cells, which may be explained by structural variations and altered binding properties of phosphopeptides. (bvsalud.org)
  • The medical research revealed a need to develop separate decision aids for women with BRCA1/2 mutations (A) without a history of cancer (previvors) and (B) with a history of unilateral breast cancer (survivors). (bvsalud.org)
  • We found that this mutant Brca1 prevents tumor formation to the same degree as does wild-type Brca1 in three different genetically engineered mouse (GEM) models of cancer. (scienceintheclassroom.org)
  • In several types of human cancer, the gene expression of Reprimo, a highly glycosylated protein, is frequently silenced via methylation of its promoter. (aacrjournals.org)
  • BRCA1 was first identified as a nuclear phosphoprotein, but has since been shown to contain different transport sequences including nuclear export and nuclear localization signals that enable it to shuttle between specific sites within the nucleus and cytoplasm, including DNA repair foci, centrosomes, and mitochondria. (hindawi.com)
  • Upon DNA damage, BRCA1 becomes hyperphosphorylated and shows alterations in subnuclear localization ( 4 ) and CtIP binding ( 2 ). (sciencemag.org)
  • Patient cells exhibited deficiency in BRCA1 and RAD51 localization to DNA-damage sites, combined with radial chromosome formation and hypersensitivity to ICL-inducing agents. (aacrjournals.org)
  • These results indicate that M1775K and V1809F mutations may change the function of the protein by affecting BRCA1 localization. (bvsalud.org)
  • Alternative splicing plays a role in modulating the subcellular localization and physiological function of this gene. (origene.com)
  • BRCA1 contains at least two nuclear localization signals and is proposed to be a tumor suppressor protein. (acris-antibodies.com)
  • The motif has the consensus sequence S..F and these residues are specially recognized by the binding pocket in the BRCT domains. (eu.org)
  • p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence. (uniprot.org)
  • section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. (uniprot.org)
  • Two ( PGluc , SRFluc , NFκBluc , and E2Fluc ) or four ( Mycluc and GAL4luc ) copies of DNA binding sequences were cloned upstream of c-fos promoter TATA sequence and luciferase genes. (nih.gov)
  • Introns contain a large number of repetitive sequences of the Alu family, amounting to 41.5% of the total gene sequence. (aacrjournals.org)
  • Aberrant pre-mRNA splicing can be more detrimental to the function of a gene than changes in the length or nature of the encoded amino acid sequence. (biomedcentral.com)
  • Approximately 11% of these ESEs (23/211) either are identical at the nucleotide level in human, primates, mouse, cow, dog and opossum Brca1 (conserved) or are detectable by ESEfinder in the same position in the Brca1 sequence (shared). (biomedcentral.com)
  • Sequence-specific transcriptional regulators function by stably bindingcognate DNA sequences followed by recruitment of both general andspecialized factors to target gene promoters. (embl.de)
  • The molecular sequence of this clone aligns with the gene accession number as a point of reference only. (origene.com)
  • There are six known isoforms of BRCA1, with isoforms 1 and 2 comprising 1863 amino acids each. (wikipedia.org)
  • The gene spans around 100 kilobases and codes for a protein containing 1863 amino acids. (news-medical.net)
  • The full-length BRCA1 cDNA encodes a large protein of 1863 amino acids ( Figure 1 ) [ 4 ]. (mdpi.com)
  • In particular, BRCA1 encodes for a protein of 1,863 amino acids and with multiple functional domains [8] . (plos.org)
  • The BRCA1 protein is a protein of 1863 amino acids. (openaccesspub.org)
  • BRCA1 enters the nucleus through the importin-alpha/beta pathway and locates at nuclear DNA replication sites. (hindawi.com)
  • We observed NF-kB p65 subunit nuclear translocation and increased gene expression of IL-1ß, IL-6, and TNF-α in the first hours following TNF-α stimulation. (bvsalud.org)
  • Transcriptional levels of p53 downstream target genes can be generally increased by p53 nuclear accumulation and the release of chromatin-bound p53 from repression state. (ijbs.com)
  • The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. (springer.com)
  • In this study we solve the crystal structures of MCPH1 natural variant (A761) C-terminal tandem BRCT domains alone as well as in complex with γH2AX tail. (rcsb.org)
  • Compared with other structures of tandem BRCT domains, the most significant differences lie in phosphopeptide binding pocket. (rcsb.org)
  • e em sua região carboxi (C) terminal um domínio BRCT em tandem, que constitui um domínio fosfopeptídeo de reconhecimento que se liga a peptídeos contendo um padrão fosfo-SXXF (S para Serina, F para Fenilalanina e X para variável). (wikipedia.org)
  • Many of these mutations eliminate the phosphopeptides-binding function of the tandem BRCT domains, preventing propogation of the DNA damage signal. (mit.edu)
  • Finally, we found that BRCA1 coimmunoprecipitates with p53, in vitro and in vivo. (nih.gov)
  • Although cleavage and polyadenylation can be studied as isolated processes in vitro , mRNA 3′ end formation in vivo is an integral component of the coupled network in which the different machines carrying out separate steps of the gene expression pathway are tethered to each other to form a gene expression factory. (pubmedcentralcanada.ca)
  • Mus101, which contains seven BRCT domains distributed throughout its length, is most similar to human TopBP1, a protein identified through its in vitro association with DNA topoisomerase IIβ. (genetics.org)
  • Atualmente as mutações encontradas no gene BRCA1 são inúmeras e são encontradas ao longo de toda a sua sequência codificadora espalhada em seus 24 exons. (wikipedia.org)
  • The frequency of conserved and shared predicted ESEs between human and mouse is higher in BRCA1 exons (2.8 per 100 nucleotides) than in introns (0.6 per 100 nucleotides). (biomedcentral.com)
  • However, the extent to which BRCA1-activated molecular pathways contribute to its tumor suppressor activity remains unclear. (aacrjournals.org)
  • The gene deletion is especially common in Asian men , notes Jenny Jakobsson Schulze, a molecular geneticist at the Karolinska University Hospital in Stockholm. (gnxp.com)
  • It is evident that the molecular cloning of this gene should bring important new insights into the function of its encoded protein. (genetics.org)
  • In second part, molecular genetics of autosomal recessive primary microcephaly including a comprehensive appraisal of the seven mapped loci (MCPH1 - MCPH7), their corresponding genes, protein products of the genes, their likely role in normal brain development and the details of the mutations reported in these genes, especially with reference to Pakistan, have been reviewed. (biomedcentral.com)
  • The comparison of the molecular mechanisms associated with the native BRCA1 protein and the mutated variant function in DNA damage response showed that the latter undergoes a reduction in its ability to modulate pathways that are critical for DNA repair and cell cycle control. (openaccesspub.org)
  • F ) Activation of mutant mdm2 promoters by BRCA1. (nih.gov)
  • The eggshell abnormalities observed in this mutant result from defective amplification of clusters of chorion protein genes, which is a form of DNA replication specific to follicle cells (for review see C alvi and S pradling 1999 ). (genetics.org)
  • The BRCA1 RING motif is flanked by alpha helices formed by residues 8-22 and 81-96 of the BRCA1 protein. (wikipedia.org)
  • A phospho specific peptide corresponding to residues surrounding S1423 of human BRCA1. (abcam.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)
  • This article on a gene on human chromosome 4 is a stub . (wikidoc.org)
  • Other alleles of mus101 causing different phenotypes were later isolated: a female sterile allele results in a defect in a tissue-specific form of DNA synthesis (chorion gene amplification) and lethal alleles cause mitotic chromosome instability that can be observed genetically and cytologically. (genetics.org)
  • The phenotypes associated with the various mus101 alleles summarized above suggest roles for the mus101 + gene product in different aspects of chromosome metabolism. (genetics.org)
  • Ohira, Seki, Nagase, Ishikawa, Nomura, Ohara: Characterization of a human homolog (BACH1) of the mouse Bach1 gene encoding a BTB-basic leucine zipper transcription factor and its mapping to chromosome 21q22.1. (antikoerper-online.de)
  • It has been proposed that mutations in MCPH genes can cause the disease phenotype by disturbing: 1) orientation of mitotic spindles, 2) chromosome condensation mechanism during embryonic neurogenesis, 3) DNA damage-response signaling, 4) transcriptional regulations and microtubule dynamics, 5) certain unknown centrosomal mechanisms that control the number of neurons generated by neural precursor cells. (biomedcentral.com)
  • The BRCA1 gene is found on the long arm of chromosome 17 (17q21) and plays a crucial role in DNA damage response. (openaccesspub.org)
  • A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 1q22-23. (springer.com)
  • 293T cells were transfected with empty vector or BRCA1 expression plasmids together with several reporter plasmids indicated, and luciferase activity was measured. (nih.gov)
  • 293T cells were cotransfected with p53, E2F1, and DP1 expression plasmids and/or BRCA1 to detect activation of PGluc or E2Fluc . (nih.gov)
  • plays an important role in maintaining the undifferentiated state of embryonic stem cells (ESCs) by preventing unscheduled expression of developmental genes (By similarity). (uniprot.org)
  • Microinjection of Swift mRNA and an mRNA for constitutively activated activin receptor (ActRIB*) into Xenopus embryos led to synergistic gene expression compared to expression of ActRIB* alone. (sciencemag.org)
  • The gene usually repairs breaks in double-stranded DNA, regulates transcription by controlling the expression of genes in response to stress, and terminates the cell cycle. (news-medical.net)
  • Ectopic expression of wild-type, but not mutated, BRCA1 in these cells rendered them less sensitive to the DNA damage agent, methyl methanesulfonate. (sciencemag.org)
  • This process, which consists in the recognition of defined poly(A) signals of the pre-mRNAs by a large cleavage/polyadenylation machinery, plays a critical role in gene expression. (pubmedcentralcanada.ca)
  • In eukaryotes, 3′ end cleavage of transcripts generated by RNA polymerase II (pol II) is a universal step of gene expression that proceeds through the recognition of cis -acting elements of the pre-messenger RNA (mRNA) [defined as the poly(A) signal] by a complex machinery. (pubmedcentralcanada.ca)
  • Search the gene expression profiles from curated DataSets in the Gene Expression Omnibus (GEO) repository. (cancerindex.org)
  • Consequently, the type and specific sites of covalent modifications in SRC3 determine the affinity for the liganded-NR, as well the association with different coactivating partners, resulting in the formation of diverse multimeric complexes which are believed to regulate distinct gene expression programs. (biomedcentral.com)
  • Expression varies depending on the nature of the gene. (origene.com)
  • BRCA1 is supported by BioGPS gene expression data to be expressed in K562. (acris-antibodies.com)
  • Western blot analysis of BRCA1 expression in HeLa (left lane) and NIH3T3 (right lane) cell lysate. (acris-antibodies.com)
  • Gene expression analyses as a prognosticator of survival in head and neck squamous cell carcinoma. (biotechsciencenews.com)
  • Cervical lymph node metastasis prediction in head and neck squamous cell carcinoma based on its gene expression. (biotechsciencenews.com)
  • BRCA1, CtIP, and ZBRK1 form a complex that coordinately represses ANG1 expression via a ZBRK1 recognition site in the ANG1 promoter. (ncku.edu.tw)
  • facilitates the association of transcription initiation factors with the promoters of the metabolism-related genes (By similarity). (uniprot.org)
  • BRCA1-deficient embryonic stem cells are hypersensitive to ionizing radiation and are defective in transcription-coupled repair of oxidative DNA damage ( 3 ). (sciencemag.org)
  • All of these gene products have been directly or indirectly implicated in transcription elongation, indicating that Rtf1 may also regulate this process. (genetics.org)
  • The BRCA1 protein and its binding transcription factors. (mdpi.com)
  • The aim of the present study is to functionally assess a set of 7 missense VUS (Q1409L, S1473P, E1586G, R1589H, Y1703S, W1718L and G1770V) located in the C-terminal region of BRCA1 by combining in silico prediction tools and structural analysis with a transcription activation (TA) assay. (plos.org)
  • BRCA1 associates with p53 and stimulates transcription in both p53 dependent and p53-independent manners. (embl-heidelberg.de)
  • We report here that BRCA1 deficiency activates the AKT oncogenic pathway, one of the most common alterations associated with human malignancy. (aacrjournals.org)
  • We present a Minimal Event Distance Aneuploidy Lineage Tree (MEDALT) algorithm that infers the evolution history of a cell population based on single-cell copy number (SCCN) profiles, and a statistical routine named lineage speciation analysis (LSA), whichty facilitates discovery of fitness-associated alterations and genes from SCCN lineage trees. (biomedcentral.com)