BRCA1 Protein: The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)Genes, BRCA1: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human CHROMOSOME 17 at locus 17q21. Mutations of this gene are associated with the formation of HEREDITARY BREAST AND OVARIAN CANCER SYNDROME. It encodes a large nuclear protein that is a component of DNA repair pathways.BRCA2 Protein: A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)Genes, BRCA2: A tumor suppressor gene (GENES, TUMOR SUPPRESSOR) located on human chromosome 13 at locus 13q12.3. Mutations in this gene predispose humans to breast and ovarian cancer. It encodes a large, nuclear protein that is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev 2000;14(11):1400-6)Germ-Line Mutation: Any detectable and heritable alteration in the lineage of germ cells. Mutations in these cells (i.e., "generative" cells ancestral to the gametes) are transmitted to progeny while those in somatic cells are not.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesMutS Homolog 2 Protein: MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.Breast Neoplasms: Tumors or cancer of the human BREAST.DNA Mismatch Repair: A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Nuclear Proteins: 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.Ovarian Neoplasms: Tumors or cancer of the OVARY. These neoplasms can be benign or malignant. They are classified according to the tissue of origin, such as the surface EPITHELIUM, the stromal endocrine cells, and the totipotent GERM CELLS.Colorectal Neoplasms, Hereditary Nonpolyposis: A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Genetic Testing: Detection of a MUTATION; GENOTYPE; KARYOTYPE; or specific ALLELES associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing.Microsatellite Instability: The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.Jews: An ethnic group with historical ties to the land of ISRAEL and the religion of JUDAISM.Genetic Predisposition to Disease: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Founder Effect: A phenomenon that is observed when a small subgroup of a larger POPULATION establishes itself as a separate and isolated entity. The subgroup's GENE POOL carries only a fraction of the genetic diversity of the parental population resulting in an increased frequency of certain diseases in the subgroup, especially those diseases known to be autosomal recessive.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.DNA-Binding Proteins: 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.Breast Neoplasms, Male: Any neoplasms of the male breast. These occur infrequently in males in developed countries, the incidence being about 1% of that in females.DNA Methylation: Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.Genetic Counseling: An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered.Neoplastic Syndromes, Hereditary: The condition of a pattern of malignancies within a family, but not every individual's necessarily having the same neoplasm. Characteristically the tumor tends to occur at an earlier than average age, individuals may have more than one primary tumor, the tumors may be multicentric, usually more than 25 percent of the individuals in direct lineal descent from the proband are affected, and the cancer predisposition in these families behaves as an autosomal dominant trait with about 60 percent penetrance.Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.Microsatellite Repeats: A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).Crossing Over, Genetic: The reciprocal exchange of segments at corresponding positions along pairs of homologous CHROMOSOMES by symmetrical breakage and crosswise rejoining forming cross-over sites (HOLLIDAY JUNCTIONS) that are resolved during CHROMOSOME SEGREGATION. Crossing-over typically occurs during MEIOSIS but it may also occur in the absence of meiosis, for example, with bacterial chromosomes, organelle chromosomes, or somatic cell nuclear chromosomes.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.DNA, Neoplasm: DNA present in neoplastic tissue.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.Frameshift Mutation: A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.Loss of Heterozygosity: The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.Heterozygote Detection: Identification of genetic carriers for a given trait.Colorectal Neoplasms: Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.Salpingectomy: Excision of one or both of the FALLOPIAN TUBES.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Family Health: The health status of the family as a unit including the impact of the health of one member of the family on the family as a unit and on individual family members; also, the impact of family organization or disorganization on the health status of its members.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.Cell Line, Tumor: A cell line derived from cultured tumor cells.Homologous Recombination: An exchange of DNA between matching or similar sequences.Meiosis: A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.Synaptonemal Complex: The three-part structure of ribbon-like proteinaceous material that serves to align and join the paired homologous CHROMOSOMES. It is formed during the ZYGOTENE STAGE of the first meiotic division. It is a prerequisite for CROSSING OVER.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Spermatocytes: Male germ cells derived from SPERMATOGONIA. The euploid primary spermatocytes undergo MEIOSIS and give rise to the haploid secondary spermatocytes which in turn give rise to SPERMATIDS.Ubiquitin-Protein Ligases: A diverse class of enzymes that interact with UBIQUITIN-CONJUGATING ENZYMES and ubiquitination-specific protein substrates. Each member of this enzyme group has its own distinct specificity for a substrate and ubiquitin-conjugating enzyme. Ubiquitin-protein ligases exist as both monomeric proteins multiprotein complexes.Fallopian Tube Neoplasms: Benign or malignant neoplasms of the FALLOPIAN TUBES. They are uncommon. If they develop, they may be located in the wall or within the lumen as a growth attached to the wall by a stalk.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.CpG Islands: Areas of increased density of the dinucleotide sequence cytosine--phosphate diester--guanine. They form stretches of DNA several hundred to several thousand base pairs long. In humans there are about 45,000 CpG islands, mostly found at the 5' ends of genes. They are unmethylated except for those on the inactive X chromosome and some associated with imprinted genes.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.Molecular Sequence Data: 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.PhthalazinesProto-Oncogene Proteins B-raf: A raf kinase subclass found at high levels in neuronal tissue. The B-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.Endometrial Neoplasms: Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Fanconi Anemia Complementation Group D2 Protein: A Fanconi anemia complementation group protein that undergoes mono-ubiquitination by FANCL PROTEIN in response to DNA DAMAGE. Also, in response to IONIZING RADIATION it can undergo PHOSPHORYLATION by ataxia telangiectasia mutated protein. Modified FANCD2 interacts with BRCA2 PROTEIN in a stable complex with CHROMATIN, and it is involved in DNA REPAIR by homologous RECOMBINATION.Penetrance: The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. (From Glossary of Genetics, 5th ed)Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Fanconi Anemia: Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group.
  • The loci can include the tumor protein 53-binding protein, 1 ( 53BP1 ) and the nuclear factor with BRCT domians protein 1 ( NFBD1 ), which take part in activation of Chk2 [ 4 ], MRN complex (consisting from double-strand break repair protein ( Mre11 ), Rad50 homolog (S. cerevisiae) ( Rad50 ) and Nijmegen breakage syndrome 1 protein ( Nibrin )) is a part of these foci, as well. (bio-rad.com)
  • We report that MSH2 (MutS homolog 2) protein interacts with the ATR (ATM- and Rad3-related) kinase to form a signaling module and regulate the phosphorylation of Chk1 and SMC1 (structure maintenance of chromosome 1). (pnas.org)
  • E3 ubiquitin ligase activity of Brca1 considerably amplifies, if Brca1 forms a complex with a Brca1 associated RING domain protein 1 ( BARD1 ) [ 6 ]. (bio-rad.com)
  • The BRCA1 - BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. (rcsb.org)
  • Component of the BRCA1 -A complex, at least composed of BRCA1 , BARD1 , UIMC1 /RAP80, ABRAXAS1 , BRCC3 / BRCC3 6, BABAM2 and BABAM1 /NBA1. (rcsb.org)
  • Component of the BRCA1 -A complex, at least composed of BRCA1 , BARD1 , UIMC1 /RAP80, ABRAXAS1 , BRCC3 / BRCC3 6, BABAM2 and BABAM1 /NBA1 (PubMed:19261746, PubMed:19261748, PubMed:19261749, PubMed:20351172). (rcsb.org)
  • 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)
  • Localization of BRCA1 is regulated by interactions with other proteins such as the BRCA1-associated RING domain protein 1 (BARD1) [ 19 , 20 ]. (mdpi.com)
  • Upon ionizing radiation induced DNA damage, CHEK2 is activated by ataxia telangiectasia mutated (ATM) and is in turn capable of phosphorylating several substrates including Cdc25A, Cdc25C, p53, and BRCA1, leading to cell cycle arrest, apoptosis, and DNA repair (reviewed in Bartek et al 1 ). (bmj.com)
  • A protein truncating mutation, 1100delC, which resides in exon 10 and abolishes the kinase function of CHEK2, has been shown to be significantly associated with a positive family history of breast cancer. (bmj.com)
  • 2 Expression of the CHEK2 protein has been shown to be absent or grossly reduced in breast tumours of heterozygous 1100delC mutation carriers, 3 and loss of the wild-type allele has been reported in a breast tumour and a sarcoma of CHEK2 mutation carriers in Li-Fraumeni syndrome (LFS). (bmj.com)
  • Interpreting variants of uncertain significance (VUS) for their effect on protein function, and therefore for the risk of developing cancer, has become a challenge in clinical practice for genetic counselling services. (openaccesspub.org)
  • High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. (beds.ac.uk)
  • MSH proteins recognize errors in the genome sequence during replication, preventing the duplication of the damaged strand and repairing single strand breaks [ 11 , 12 ]. (hindawi.com)
  • The fact that defects in three of five known human being RecQ helicases cause genome instability diseases suggests that this family of proteins plays key tasks in keeping the integrity of the genome. (bio-zentrum.com)
  • In addition, BLM has been found in the BRCA1-connected genome surveillance complex, BASC (46). (bio-zentrum.com)
  • Interactions between apoptosis and genome-maintenance mechanisms have been extensively documented and include transactivation-independent and -dependent functions, in which the tumor-suppressor protein p53 works as a molecular node in the DNA-damage response. (scribd.com)
  • Genome-maintenance mechanisms are intimately linked to apoptotic components, as indicates the high number of proteins that interact with the tumor-suppressor protein p53. (scribd.com)
  • The mutant BRCA1/2 were eliminated or destabilized by nonsense-mediated mRNA decay (NMD) and lead to a state of haploinsufficiency ( 8 ). (aacrjournals.org)
  • In our present study, we confirmed that both mRNA and protein expression of FILIP1L were downregulated in ovarian cancer cells compared with normal ovarian epithelial cells. (aacrjournals.org)
  • BRCA1 mRNA expression and BRCA1 protein expression were determined by quantitative RT-PCR and western blot, respectively and BRCA1 promoter activities were examined under these conditions. (biomedcentral.com)
  • Depletion of c-Myc was found to be correlated with reduced expression levels of BRCA1 mRNA and BRCA1 protein. (biomedcentral.com)
  • Elevated expression of XPO1 mRNA and/or protein has been observed in many types of cancer, and high levels of XPO1 expression are associated with poor prognosis in cancer patients [ 2 - 5 ]. (oncotarget.com)
  • There react immune particles behind N-terminal download Interpretability Issues in Fuzzy Modeling 2003, but in the disruption of signaling a intestinal nephrin, this pre-mRNA of expression cell is protein-RNA in state form and is partners. (evakoch.com)
  • Besides mRNA splicing, IT provides a common framework to evaluate potential affinity changes in transcription factor (TFBSs), splicing regulatory (SRBSs), and RNA-binding protein (RBBSs) binding sites following mutation. (uwo.ca)
  • FBL17 was reported to control the stability of the CYCLIN-DEPENDENT KINASE inhibitor KIP-RELATED PROTEIN (KRP), which may underlie the drastic reduction in cell division activity in both shoot and root apical meristems observed in fbl17 loss-of-function mutants. (plantphysiol.org)
  • DNA damage-dependent activation of the breast and ovarian cancer susceptibility protein 1 ( Brca1 ) occurs via activation of ataxia telangiectasia mutated serine-protein kinase ( ATM ) [ 1 ] or ataxia telangiectasia and Rad3 related protein kinase ( ATR ) [ 2 ]. (bio-rad.com)
  • Activating phosphorylation of the Chk1 kinase was increased and total protein levels of CDC25C reduced, further implicating the DNA damage pathway in the induction of arrest. (core.ac.uk)
  • Darnell [ 8 ] classified TFs having cancerous or oncogenic potential into three main kinds - steroid receptors ( e.g . oestrogen receptors in breast cancer and androgen receptors in prostate cancer), resident nuclear proteins activated by serine kinase cascades ( e.g . (biomedcentral.com)
  • In humans, the central checkpoint kinases ATM (ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related), and the RFC (replication factor C)-like checkpoint protein Rad17/RFC2-5 complex have been demonstrated to function upstream of the DNA damage response pathway for the activation of the downstream checkpoint kinase Chk1 by phosphorylation ( 3 ). (pnas.org)
  • A subset of kinase substrates are recognized by the S/T-Q cluster domain (SCD), which contains motifs of serine (S) or threonine (T) followed by a glutamine (Q). However, the full repertoire of proteins and pathways controlled by Tel1 and Mec1 is unknown. (biomedcentral.com)
  • the interaction occurs only in the presence of PALB2 which serves as the bridging protein. (rcsb.org)
  • Similarly, in mammalian cells, the CKI protein p27 Kip1 becomes unstable when cells enter S phase, as targeted by the SCF Skp2 (Skp2 being a Leu rich repeat-containing F-box protein) ubiquitin ligase (for a review, see Starostina and Kipreos, 2012 ). (plantphysiol.org)
  • 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. (rcsb.org)
  • The E3 ubiquitin-protein ligase activity is required for its tumor suppressor function. (rcsb.org)
  • The microbial complex of Human waste Virus( HIV) stem starts associated in ubiquitin-26S of proteins of specificities reviewed by the antioxidant and cells more low. (erik-mill.de)
  • The glycosyl variety( now disrupted to as the UCH37 protein) converts the multiprotein by which the synaptic ubiquitin small( Vertebrate) depends branched from negative roles in the protein ionic and called entirely to its 11-cis budget caspase-1 for another identification gut. (erik-mill.de)
  • In a previous study we reported that BRCA1-related breast carcinomas show a distinct genomic profile as determined by comparative genomic hybridization (CGH). (aacrjournals.org)
  • We have previously shown that the profile of BRCA1-related tumors, as assessed by comparative genomic hybridization (CGH), is distinct from sporadic breast tumors. (aacrjournals.org)
  • The mismatch repair (MMR) proteins play key roles in postreplicational mispair correction that is essential for genomic stability ( 7 ). (pnas.org)
  • Together, these domains allow PARP-1 to interact with genomic DNA and chromatin, poly(ADP-ribosyl)ate a variety of nuclear target proteins, and regulate nuclear functions. (activemotif.com)
  • Moreover, Fanconi anemia proteins/ Brca1 pathway participates in DNA interstrand cross-link (ICL) repair [ 15 ]. (bio-rad.com)
  • FA pathway proteins are involved in the intricate cellular signalling that occurs following DNA damage. (els.net)
  • FA pathway proteins are involved in regulating oxidative stress. (els.net)
  • We found that phosphorylation of Chk1 by ATR also requires checkpoint proteins Rad17 and replication protein A. In contrast, phosphorylation of SMC1 by ATR is independent of Rad17 and replication protein A, suggesting that the signaling pathway leading to SMC1 phosphorylation is distinct from that mediated by the checkpoint proteins. (pnas.org)
  • Upon exposure to MNNG and crosslinking agents, cells deficient in MMR proteins exhibit impaired G 2 /M cell cycle arrest, reduced activation of the p53/p73 apoptosis pathway, and resistance to the cytotoxicity of these DNA-damaging agents ( 12 - 14 ). (pnas.org)
  • These protein complexes participate in many cellular functions, including vesicle transport and fusion, fragmentation and reassembly of the golgi stacks during mitosis, nuclear envelope formation and spindle disassembly following mitosis, cell cycle regulation, DNA damage repair, apoptosis, B- and T-cell activation, NF-κB-mediated transcriptional regulation, endoplasmic reticulum (ER)-associated degradation and protein degradation (4). (cellsignal.com)
  • Background: High mobility group (HMG) proteins are a superfamily of abundant and ubiquitous nuclear proteins that bind DNA without sequence specificity and induce structural changes to the chromatin fiber to regulate access to the underlying DNA. (cellsignal.com)
  • Notably, we observed that the FBL17 protein is recruited at nuclear foci upon double-strand break induction and colocalizes with γH2AX, but only in the presence of RETINOBLASTOMA RELATED1. (plantphysiol.org)
  • Phosphorylated by ATM and ATR histones ( H2AX ) are co-localized together with some proteins to form nuclear foci at DNA damage sites. (bio-rad.com)
  • In addition, activated by Brca1 , p53 participates in BER by exciting transcription of proliferating cell nuclear antigen ( PCNA ) and stimulating activity of the endonuclease III-like 1 enzyme ( Nth1 ). (bio-rad.com)
  • Within chromatin, FANCD2 and FANCI colocalise with DNA repair proteins including the downstream effector, FA proteins, at sites of DNA damage in nuclear foci. (els.net)
  • SCP3 (Synaptonemal complex protein 3) is a DNA-binding nuclear protein that belongs to XLR/SYCP3 family and is an essential structural component of the transverse filaments of synaptonemal complexes formed between homologous chromosomes during meiotic prophase. (novusbio.com)
  • PARP-1 exhibits physical and functional interactions with (1) core histones, (2) the linker histone H1, (3) topoisomerases I and II, and (4) DNA binding transcription factors such as NFκB, B-MYB, Oct-1, nuclear receptors, YY1, TBP, and the HTLV Tax-1 protein. (activemotif.com)
  • For example, following DNA damage induced by mitomycin C (MMC), an FA protein, FANCD2, becomes monoubiquitinated and redistributes into nuclear foci, where it colocalizes with BNIP3 CH5424802 BRCA1 (12). (bio-zentrum.com)
  • The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population. (biomedcentral.com)
  • Pathogenic variants in BRCA1 confer susceptibility to breast and ovarian cancer. (springer.com)
  • Since the identification of BRCA1 pathogenic variants allows for specific preventive and surveillance measures, the establishment of the pathogenicity of BRCA1 variants is crucial for clinical management of cancer patients and family members at risk of breast and ovarian malignancy. (springer.com)
  • Background: Valosin-containing protein (VCP) is a highly conserved and abundant 97 kDa protein that belongs to the AAA (ATPase associated with a variety of cellular activities) family of proteins. (cellsignal.com)
  • The HMGN family of proteins, which includes five members (HMGN1-5), is characterized by the presence of several conserved protein domains: a positively charged domain, a nucleosome binding domain, and an acidic C-terminal chromatin-unfolding domain (1,2). (cellsignal.com)
  • Another epigenetic mechanism reducing MLH1 expression is over-expression of miR-155. (wikipedia.org)
  • Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. (beds.ac.uk)
  • Epigenetic inactivation of BRCA1 is associated with aberrant expression of CTCF and DNA methyltransferase (DNMT3B) in some sporadic breast tumours. (semanticscholar.org)