Ataxia Telangiectasia: An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).Ataxia Telangiectasia Mutated Proteins: 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.Telangiectasis: Permanent dilation of preexisting blood vessels (CAPILLARIES; ARTERIOLES; VENULES) creating small focal red lesions, most commonly in the skin or mucous membranes. It is characterized by the prominence of skin blood vessels, such as vascular spiders.Telangiectasia, Hereditary Hemorrhagic: An autosomal dominant vascular anomaly characterized by telangiectases of the skin and mucous membranes and by recurrent gastrointestinal bleeding. This disorder is caused by mutations of a gene (on chromosome 9q3) which encodes endoglin, a membrane glycoprotein that binds TRANSFORMING GROWTH FACTOR BETA.Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or PERIPHERAL NERVE DISEASES. Motor ataxia may be associated with CEREBELLAR DISEASES; CEREBRAL CORTEX diseases; THALAMIC DISEASES; BASAL GANGLIA DISEASES; injury to the RED NUCLEUS; and other conditions.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.Cerebellar Ataxia: Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)Cell Cycle Proteins: 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.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Retinal Telangiectasis: A group of rare, idiopathic, congenital retinal vascular anomalies affecting the retinal capillaries. It is characterized by dilation and tortuosity of retinal vessels and formation of multiple aneurysms, with different degrees of leakage and exudates emanating from the blood vessels.Friedreich Ataxia: An autosomal recessive disease, usually of childhood onset, characterized pathologically by degeneration of the spinocerebellar tracts, posterior columns, and to a lesser extent the corticospinal tracts. Clinical manifestations include GAIT ATAXIA, pes cavus, speech impairment, lateral curvature of spine, rhythmic head tremor, kyphoscoliosis, congestive heart failure (secondary to a cardiomyopathy), and lower extremity weakness. Most forms of this condition are associated with a mutation in a gene on chromosome 9, at band q13, which codes for the mitochondrial protein frataxin. (From Adams et al., Principles of Neurology, 6th ed, p1081; N Engl J Med 1996 Oct 17;335(16):1169-75) The severity of Friedreich ataxia associated with expansion of GAA repeats in the first intron of the frataxin gene correlates with the number of trinucleotide repeats. (From Durr et al, N Engl J Med 1996 Oct 17;335(16):1169-75)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.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.Spinocerebellar Ataxias: A group of dominantly inherited, predominately late-onset, cerebellar ataxias which have been divided into multiple subtypes based on clinical features and genetic mapping. Progressive ataxia is a central feature of these conditions, and in certain subtypes POLYNEUROPATHY; DYSARTHRIA; visual loss; and other disorders may develop. (From Joynt, Clinical Neurology, 1997, Ch65, pp 12-17; J Neuropathol Exp Neurol 1998 Jun;57(6):531-43)Radiation, Ionizing: 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.Checkpoint Kinase 2: Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.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.Gait Ataxia: Impairment of the ability to coordinate the movements required for normal ambulation (WALKING) which may result from impairments of motor function or sensory feedback. This condition may be associated with BRAIN DISEASES (including CEREBELLAR DISEASES and BASAL GANGLIA DISEASES); SPINAL CORD DISEASES; or PERIPHERAL NERVOUS SYSTEM DISEASES.Gamma Rays: Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.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.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.Epistaxis: Bleeding from the nose.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Pyrones: Keto-pyrans.Activin Receptors, Type II: One of the two types of ACTIVIN RECEPTORS. They are membrane protein kinases belonging to the family of PROTEIN-SERINE-THREONINE KINASES. The major type II activin receptors are ActR-IIA and ActR-IIB.Arteriovenous Malformations: Abnormal formation of blood vessels that shunt arterial blood directly into veins without passing through the CAPILLARIES. They usually are crooked, dilated, and with thick vessel walls. A common type is the congenital arteriovenous fistula. The lack of blood flow and oxygen in the capillaries can lead to tissue damage in the affected areas.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.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.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.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.Dose-Response Relationship, Radiation: The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.Cell Cycle: 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.Nijmegen Breakage Syndrome: A chromosome instability syndrome resulting from a defective response to DNA double-strand breaks. In addition to characteristic FACIES and MICROCEPHALY, patients have a range of findings including RADIOSENSITIVITY, immunodeficiency, increased cancer risk, and growth retardation. Causative mutations occur in the NBS1 gene, located on human chromosome 8q21. NBS1 codes for nibrin, the key regulator protein of the R/M/N (RAD50/MRE11/NBS1) protein complex which senses and mediates cellular response to DNA DAMAGE caused by IONIZING RADIATION.Streptonigrin: Complex cytotoxic antibiotic obtained from Streptomyces flocculus or S. rufochronmogenus. It is used in advanced carcinoma and causes leukopenia.CREST Syndrome: A mild form of LIMITED SCLERODERMA, a multi-system disorder. Its features include symptoms of CALCINOSIS; RAYNAUD DISEASE; ESOPHAGEAL MOTILITY DISORDERS; sclerodactyly, and TELANGIECTASIS. When the defect in esophageal function is not prominent, it is known as CRST syndrome.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.G2 Phase: The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.DNA Replication: The process by which a DNA molecule is duplicated.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.Microcephaly: A congenital abnormality in which the CEREBRUM is underdeveloped, the fontanels close prematurely, and, as a result, the head is small. (Desk Reference for Neuroscience, 2nd ed.)Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Heterozygote: An individual having different alleles at one or more loci regarding a specific character.X-Rays: Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Infrared Rays: That portion of the electromagnetic spectrum usually sensed as heat. Infrared wavelengths are longer than those of visible light, extending into the microwave frequencies. They are used therapeutically as heat, and also to warm food in restaurants.Genes, cdc: Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Cell Line, Tumor: A cell line derived from cultured tumor cells.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.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.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.G2 Phase Cell Cycle Checkpoints: CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE.Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.Telomeric Repeat Binding Protein 2: A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Iron-Binding Proteins: Proteins that specifically bind to IRON.Cell Cycle Checkpoints: Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Cardiac Output, High: A state of elevated cardiac output due to conditions of either increased hemodynamic demand or reduced cardiac oxygen output. These conditions may include ANEMIA; ARTERIOVENOUS FISTULA; THYROTOXICOSIS; PREGNANCY; EXERCISE; FEVER; and ANOXIA. In time, compensatory changes of the heart can lead to pathological form of high cardiac output and eventual HEART FAILURE.Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.Activin Receptors, Type I: One of the two types of ACTIVIN RECEPTORS or activin receptor-like kinases (ALK'S). There are several type I activin receptors. The major active ones are ALK-2 (ActR-IA) and ALK-4 (ActR-IB).MorpholinesMutation, 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)Comet Assay: A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.HeLa Cells: 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.Chromosome Disorders: Clinical conditions caused by an abnormal chromosome constitution in which there is extra or missing chromosome material (either a whole chromosome or a chromosome segment). (from Thompson et al., Genetics in Medicine, 5th ed, p429)Homozygote: An individual in which both alleles at a given locus are identical.Bleomycin: A complex of related glycopeptide antibiotics from Streptomyces verticillus consisting of bleomycin A2 and B2. It inhibits DNA metabolism and is used as an antineoplastic, especially for solid tumors.Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases.Cerebellum: The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills.Chromosomes, Human, Pair 11: A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Syndrome: A characteristic symptom complex.Immunologic Deficiency Syndromes: Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.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.DNA Ligases: 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 126.96.36.199 (ATP) and EC 188.8.131.52 (NAD).Cell Aging: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.G1 Phase: The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.Mice, 129 Strain: Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.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.Chromosomal Proteins, Non-Histone: Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Chromosomes, Human, Pair 14: A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.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)Machado-Joseph Disease: A dominantly-inherited ATAXIA first described in people of Azorean and Portuguese descent, and subsequently identified in Brazil, Japan, China, and Australia. This disorder is classified as one of the SPINOCEREBELLAR ATAXIAS (Type 3) and has been associated with a mutation of the MJD1 gene on chromosome 14. Clinical features include progressive ataxia, DYSARTHRIA, postural instability, nystagmus, eyelid retraction, and facial FASCICULATIONS. DYSTONIA is prominent in younger patients (referred to as Type I Machado-Joseph Disease). Type II features ataxia and ocular signs; Type III features MUSCULAR ATROPHY and a sensorimotor neuropathy; and Type IV features extrapyramidal signs combined with a sensorimotor neuropathy. (From Clin Neurosci 1995;3(1):17-22; Ann Neurol 1998 Mar;43(3):288-96)Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Retinal DiseasesRecombination, 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.HCT116 Cells: Human COLORECTAL CARCINOMA cell line.Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.Poly(ADP-ribose) Polymerases: 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.Lymphoma: A general term for various neoplastic diseases of the lymphoid tissue.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Gene Rearrangement, T-Lymphocyte: Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Leucine Zippers: DNA-binding motifs formed from two alpha-helixes which intertwine for about eight turns into a coiled coil and then bifurcate to form Y shaped structures. Leucines occurring in heptad repeats end up on the same sides of the helixes and are adjacent to each other in the stem of the Y (the "zipper" region). The DNA-binding residues are located in the bifurcated region of the Y.Angiodysplasia: Acquired degenerative dilation or expansion (ectasia) of normal BLOOD VESSELS, often associated with aging. They are isolated, tortuous, thin-walled vessels and sources of bleeding. They occur most often in mucosal capillaries of the GASTROINTESTINAL TRACT leading to GASTROINTESTINAL HEMORRHAGE and ANEMIA.Trinucleotide Repeat Expansion: An increased number of contiguous trinucleotide repeats in the DNA sequence from one generation to the next. The presence of these regions is associated with diseases such as FRAGILE X SYNDROME and MYOTONIC DYSTROPHY. Some CHROMOSOME FRAGILE SITES are composed of sequences where trinucleotide repeat expansion occurs.cdc25 Phosphatases: A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.Phosphatidylinositol 3-Kinases: Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.Topoisomerase I Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE I.Translocation, Genetic: A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Karyotyping: Mapping of the KARYOTYPE of a cell.Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.Intracranial Arteriovenous Malformations: Congenital vascular anomalies in the brain characterized by direct communication between an artery and a vein without passing through the CAPILLARIES. The locations and size of the shunts determine the symptoms including HEADACHES; SEIZURES; STROKE; INTRACRANIAL HEMORRHAGES; mass effect; and vascular steal effect.Proto-Oncogene Proteins c-abl: Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.Androstadienes: Derivatives of the steroid androstane having two double bonds at any site in any of the rings.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Proto-Oncogene Proteins c-mdm2: An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.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.Protein Binding: 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.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Telomerase: An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.Mice, Mutant Strains: Mice bearing mutant genes which are phenotypically expressed in the animals.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
... has been shown to interact with: Ataxia telangiectasia and Rad3 related, Ataxia telangiectasia mutated, HUS1, NHP2L1, ... Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene. The protein encoded by this gene ... "Toward a Catalog of Human Genes and Proteins: Sequencing and Analysis of 500 Novel Complete Protein Coding Human cDNAs". Genome ... This protein binds to chromatin prior to DNA damage and is phosphorylated by ATR after the damage. This protein recruits the ...
... has been shown to interact with SMC3 and Ataxia telangiectasia mutated. SMC protein Cornelia de Lange Syndrome GRCh38: ... Structural maintenance of chromosomes protein 1A is a protein that in humans is encoded by the SMC1A gene. Proper cohesion of ... indicating a potential role for this protein in DNA repair. This gene, which belongs to the SMC gene family, is located in an ... Therefore, the encoded protein is thought to be an important part of functional kinetochores. In addition, this protein ...
... protein and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint ... BRCA1-associated ATM activator 1 is a protein in humans that is encoded by the BRAT1 gene. The protein encoded by this ... The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. GRCh38: ... "Entrez Gene: BRCA1-associated ATM activator 1". Human BRAT1 genome location and BRAT1 gene details page in the UCSC Genome ...
Ataxia telangiectasia mutated has been shown to interact with: Abl gene, BRCA1, Bloom syndrome protein, DNA-PKcs, FANCD2, ... An earlier name for the protein that is still widely used, ataxia-telangiectasia mutated, reflected that the disorder ataxia- ... NIH/UW entry on Ataxia telangiectasia OMIM entries on Ataxia telangiectasia Human ATM genome location and ATM gene details page ... "Entrez Gene: ATM ataxia telangiectasia mutated (includes complementation groups A, C and D)". Lee JH, Paull TT (December 2007 ...
... has been shown to interact with: Abl gene, Ataxia telangiectasia mutated, BARD1, BRCA1, BRCA2, BRCC3, BRE, Bloom syndrome ... RAD51 is a eukaryotic gene. The enzyme encoded by this gene is a member of the RAD51 protein family which assists in repair of ... "RadA protein is an archaeal RecA protein homolog that catalyzes DNA strand exchange". Genes & Development. 12 (9): 1248-1253. ... In mammals, microRNAs (miRNAs) regulate about 60% of the transcriptional activity of protein-encoding genes. Some miRNAs also ...
... has been shown to interact with Mdm2 and Ataxia telangiectasia mutated. Abnormalities in this gene are one of the causes ... The gene encoding the RRM2B protein is located on chromosome 8, at position 8q23.1. The gene and its products are also known by ... Microarray analysis reveals defective induction of p53 target genes and upregulation of chaperone genes". Oncogene. 24 (28): ... "Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in ...
Ataxia telangiectasia mutated (ATM) Ataxia telangiectasia and Rad3 related (ATR) 5' AMP-activated protein kinase (AMPK) RAF ... recessive disease in which the genes required to express the tumor-suppressant proteins that form the TSC complex is mutated or ... 5' adenosine-monophospate-activated protein kinase (AMPK) has also been found to be an effector for RHEB. AMPK is a protein ... "Isolation of cDNA and genomic clones of a human Ras-related GTP-binding protein gene and its chromosomal localization to the ...
... a protein), MAPRE2 (Microtubule-associated protein RP/EB, a protein), ATM (Ataxia telangiectasia mutated, a protein kinase), ... TERF1 has been shown to interact with: Abl gene, Ataxia telangiectasia mutated, MAPRE1, NME1, PINX1 SALL1, TINF2, TNKS2, and ... TERF 1 gene encodes a telomere specific protein which is a component of the telomere nucleoprotein complex. This protein is ... This gene encodes a telomere specific protein which is a component of the shelterin nucleoprotein complex. This protein is ...
... the ataxia telangiectasia-mutated ATM kinase, and 53BP1. Because Artemis can remove damaged ends from DNA, it has been proposed ... "Protein Knowledgebase: Gene DCLRE1C - DNA cross-link repair 1C protein (Protein artemis)". Retrieved June 2, 2011. de Villartay ... Artemis is a protein that in humans is encoded by the DCLRE1C (DNA cross-link repair 1C) gene. Artemis is a nuclear protein ... "Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated ...
2000). "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder". ... Double-strand break repair protein MRE11A is a protein that in humans is encoded by the MRE11A gene. This gene encodes a ... By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 ... This gene has a pseudogene on chromosome 3. Alternative splicing of this gene results in two transcript variants encoding ...
"Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM". J. Biol. Chem. ... Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome. The Bloom ... the causative gene of Bloom syndrome) protein translocation into the nucleus by a nuclear localization signal". Biochem. ... "Direct association of Bloom's syndrome gene product with the human mismatch repair protein MLH1". Nucleic Acids Res. 29 (21): ...
... apolipoprotein A-IV ARCN1 encoding protein Archain 1 ASRGL1: encoding enzyme L-asparaginase ATM: ataxia telangiectasia mutated ... So CCDS's gene number prediction represents a lower bound on the total number of human protein-coding genes. See also: Category ... encoding protein Uncharacterized protein C11orf16 C11orf49: encoding protein UPF0705 protein C11orf49 C11orf52 encoding protein ... encoding protein Acrosomal protein SP-10 AKIP1: A kinase interacting protein 1 ALKBH3 encoding protein AlkB homolog 3, alpha- ...
... or FRAP-related protein 1 (FRP1) is an enzyme that, in humans, is encoded by the ATR gene. ATR belongs to the ... Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and ... Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) ... Chen J (Sep 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following ...
M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity". The Journal of Biological Chemistry. 275 ... The CHK2 protein encoded by the CHEK2 gene is a serine threonine kinase. The protein consists of 543 amino acids and the ... Educational resources Gene Reviews Gene Tests CHEK2 protein, human at the US National Library of Medicine Medical Subject ... The CHEK2 gene encodes for checkpoint kinase 2 (CHK2), a protein that acts a tumor suppressor. CHK2 regulates cell division, ...
Gatei, M; Zhou B B, Hobson K, Scott S, Young D, Khanna K K (2001). «Ataxia telangiectasia mutated (ATM) kinase and ATM and Rad3 ... Identification of a RING protein that can interact in vivo with the BRCA1 gene product». Nat. Genet. 14 (4): 430-40. PMID ... Chen, J (2000). «Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic ... Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response». Nature. 406 (6792): 210-5. PMID ...
At a DSB, MRE11-RAD50-NBS1 (MRN) protein complex recruits ataxia telangiectasia mutated (ATM) kinase which phosphorylates ... HMGA2 protein specifically targets the promoter of ERCC1, thus reducing expression of this DNA repair gene. ERCC1 protein ... April 2003). "Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in ... BRCA-mutated ovarian cancer, and BRCA-mutated serous ovarian cancer. Other genes in the MMEJ pathway are also over-expressed in ...
... has been shown to interact with: Ataxia telangiectasia mutated, BRCA1, H2AFX, MRE11A, Rad50, and TERF2 GRCh38: Ensembl ... Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the NBN gene. Nibrin is a protein associated with ... The central role is carried out by ataxia telangiectasia mutated (ATM) by activating the DSB signaling cascade, phosphorylating ... It has been linked to mutations within exons 6-10 in the NBS1 gene which results in a truncated protein. Characteristics of NBS ...
Matsuoka S, Rotman G, Ogawa A, Shiloh Y, Tamai K, Elledge SJ (2000). "Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo ... "The polo-like protein kinases Fnk and Snk associate with a Ca(2+)- and integrin-binding protein and are regulated dynamically ... a cell cycle gene localized to 8p21, is downregulated in head and neck cancer". Genes Chromosomes Cancer. 27 (3): 332-6. doi: ... Li B, Ouyang B, Pan H, Reissmann PT, Slamon DJ, Arceci R, Lu L, Dai W (1996). "Prk, a cytokine-inducible human protein serine/ ...
Ataxia telangiectasia mutated) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved ... April 2003). "Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in ... BRCA-mutated ovarian cancer, and BRCA-mutated serous ovarian cancer. Other genes in the MMEJ pathway are also over-expressed in ... If a cell retains DNA damage, transcription of a gene can be prevented, and thus translation into a protein will also be ...
For instance two dominant-negative germ line mutations were identified in the Ataxia telangiectasia mutated (ATM) gene which ... For example, in humans the Hb gene locus is responsible for the Beta-chain protein (HBB) that is one of the two globin proteins ... The bb combination is not dominant to the A allele: rather, the B gene shows recessive epistasis to the A gene, because the B ... Such dominant-negative mutations occur in the tumor suppressor gene p53. The P53 wild-type protein is normally present ...
For instance two dominant-negative germ line mutations were identified in the Ataxia telangiectasia mutated (ATM) gene which ... For example, in humans the Hb gene locus is responsible for the Beta-chain protein (HBB) that is one of the two globin proteins ... an aggregate of multiple copies of the same protein, otherwise known as a homomultimeric protein or homooligomeric protein. In ... Such dominant-negative mutations occur in the tumor suppressor gene p53. The P53 wild-type protein is normally present as a ...
Ataxia telangiectasia mutated, ATR and DNA-PKcs) are responsible for this phosphorylation, especially ATM. The modification can ... This protein, heterochromatin protein 1 (HP1)-beta (CBX1), is bound to histone H3 methylated on lysine 9 (H3K9me). Half-maximum ... H2AFX (H2A histone family, member X) is one of several genes coding for histone H2A. In humans and other eukaryotes, the DNA is ... Other proteins that stably assemble on the extensive γH2AX-modified chromatin are the MRN complex (a protein complex consisting ...
In the presence of ionizing radiation (IR), the Smc1 subunit of cohesin is phosphorylated by the ataxia telangiectasia mutated ... The proteins encoded by these genes all function in the chromosome cohesion pathway that is employed in the cohesion of sister ... Though the protein was originally identified as a Topoisomerase I redundant factor, the TRF4 gene product was later shown to be ... The Pds5 gene was also identified in yeast as necessary for the establishment of cohesion. In humans, the gene has two homologs ...
FANCI Ataxia telangiectasia mutated, BARD1, BRCA1. BRCA2, FANCE, HTATIP, and MEN1. GRCh38: Ensembl release 89: ENSG00000144554 ... This gene encodes the protein for complementation group D2. This protein is monoubiquitinated in response to DNA damage, ... Fanconi anemia group D2 protein is a protein that in humans is encoded by the FANCD2 gene. The Fanconi anemia complementation ... Castillo P, Bogliolo M, Surralles J (2011). "Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in ...
Ataxia telangiectasia mutated (ATM) is a kinase that (similar to mTOR) can phosphorylate KAP1 resulting in the switch from ... KRAB-associated protein-1), is a protein that in humans is encoded by the TRIM28 gene. The protein encoded by this gene ... "Entrez Gene: TRIM28 tripartite motif-containing 28". Iyengar, Sushma; Farnham, Peggy (2011-07-29). "KAP1 Protein: An Enigmatic ... The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of ...
Other protein degradation genes that can cause ALS when mutated include VCP, OPTN, TBK1, and SQSTM1. Three genes implicated in ... Friedreich's ataxia. *Ataxia-telangiectasia. MND. *UMN only: *Primary lateral sclerosis. *Pseudobulbar palsy ... There are a number of ALS genes that encode for RNA-binding proteins. The first to be discovered was TDP-43 protein, a ... C9orf72 is the most commonly mutated gene in ALS and causes motor neuron death through a number of mechanisms. The ...
The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein ... The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein ... The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein ... The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein ...
The second experimental therapeutic approach for hereditary cerebellar ataxias is neurotransplantation. Grafted cells might ... shown to affect the pathogenetic process and thereby to delay the progress of the disease in mouse models of cerebellar ataxias ... Thus, silencing of the mutated genes expression might be helpful. In a mouse model of spinocerebellar ataxia type 3 (SCA3), ... Weaver mice carry the missense Grik Wv mutation of the gene encoding a G-protein coupled with inward rectifying potassium ...
Learn about this gene and related health conditions. ... The ATM gene provides instructions for making a protein that is ... ataxia telangiectasia mutated (includes complementation groups A, C and D). *ataxia telangiectasia mutated protein ... Hall J. The Ataxia-telangiectasia mutated gene and breast cancer: gene expression profiles and sequence variants. Cancer Lett. ... Ataxia-telangiectasia. Researchers have identified several hundred mutations in the ATM gene that cause ataxia-telangiectasia. ...
Mutation at intronic repeats of the ataxia-telangiectasia mutated (ATM) gene and ATM protein loss in primary gastric cancer ... Mutation at Intronic Repeats of the Ataxia-Telangiectasia Mutated (ATM) Gene and ATM Protein Loss in Primary Gastric Cancer ... Mutation at Intronic Repeats of the Ataxia-Telangiectasia Mutated (ATM) Gene and ATM Protein Loss in Primary Gastric Cancer ... Mutation at Intronic Repeats of the Ataxia-Telangiectasia Mutated (ATM) Gene and ATM Protein Loss in Primary Gastric Cancer ...
May play a role in vesicle and/or protein transport. Could play a role in T-cell development, gonad and neurological function. ... Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic ... Serine-protein kinase ATM (EC:184.108.40.206). Alternative name(s):. Ataxia telangiectasia mutated homolog. Short name: ... Protein-protein interaction databases. STRING: functional protein association networks. More...STRINGi. 9823.ENSSSCP00000019250 ...
Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An ... Ataxia Telangiectasia Mutated Proteins / genetics* * Chromatin / genetics * DNA Damage / radiation effects * DNA-Binding ... Gene Expression Regulation / radiation effects * Green Fluorescent Proteins / genetics * Humans * Mice * Nuclear Proteins / ... Ataxia telangiectasia mutated and Rad3-related (ATR) kinase is a key factor activated by DNA damage and replication stress. An ...
IRS-1 protein binds to several oncogene proteins. Oxidative stress and reactive oxygen species (ROS) are involved in the ... AMP-activated protein kinase; ATM, Ataxia-telangiectasia mutated; LKB, Liver kinase B; DMEM, Dulbeccos modified Eagle medium; ... Gene Expression Regulation, Neoplastic. Humans. Insulin Receptor Substrate Proteins* / genetics, metabolism. Mice. NIH 3T3 ... Oxidative stress activates AMPK by stimulation of ataxia-telangiectasia mutated protein (ATM), an upstream activator of AMPK [ ...
Ataxia-telangiectasia mutated (ATM) also can activate transcription of secondary molecules including p53, which regulate genes ... The ataxia-telangiectasia mutated (ATM) protein physically interacts with the tyrosine kinase c-Abl (20, 21) and is required ... Response to DNA damage is detected by the ataxia-telangiectasia mutated (ATM) (reviewed in refs. 12 and 13), which activates ... To generate G2A-GFP fusion protein, the murine G2A gene was fused to green fluorescence protein (GFP) in pEGFP-N1 vector ( ...
ADA =adenosine deaminase; ATM = ataxia telangiectasia-mutated; DOCK = dedicator of cytokinesis; IL-2RG = IL-2 receptor gamma; ... protein tyrosine phosphatase, receptor type, C; RAG = recombination activating gene; STAT = signal transducer and activator of ... Examples are ataxia-telangiectasia, cartilage-hair hypoplasia, DiGeorge syndrome, hyper-IgE syndrome, and Wiskott-Aldrich ... Ataxia, telangiectasias, recurrent sinopulmonary infections, endocrine abnormalities (eg, gonadal dysgenesis, testicular ...
AT3G48190, ARABIDOPSIS THALIANA ATAXIA-TELANGIECTASIA MUTATED, ATATM, PIG1, ataxia-telangiectasia mutated, pcd in male ... Serine/Threonine-kinase ATM-like protein [Arabidopsis thaliana (thale cress)]. Chromosome 3, NC_003074.8 (17801289..17828553). ... ataxia telangiectasia mutated [Mus musculus (house mouse)]. Chromosome 9, NC_000075.6 (53437122..53536816, complement). ... db=gene,term=atm[gene]%20AND%20alive[prop]%20NOT%20newentry[gene],query=1,qty=276,blobid=NCID_1_130036433_220.127.116.11_9001_ ...
Functional link between BLM defective in Blooms syndrome and the ataxia-telangiectasia mutated protein, ATM.J Blol Chem. 277 ... Functional link between BLM defective in Blooms syndrome and the ataxia-telangiectasia mutated protein, ATM.J Biol Chem. 277 ... Functional link between BLM defective in Blooms syndrome and the ataxia-telangiectasia-mutated protein, ATMJ Biol Chem.. 277 ... Publications] Kaneko H, Kondo N et al: BLM (the causative gene of Bloom syndrome) protein translocation into the nucleus by a ...
... proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium ... Protein Coding), DNA Cross-Link Repair 1C, including: function, ... Publications for DCLRE1C Gene * Ataxia-telangiectasia-mutated ... Summaries for DCLRE1C Gene Entrez Gene Summary for DCLRE1C Gene. * This gene encodes a nuclear protein that is involved in V(D) ... Domains & Families for DCLRE1C Gene Gene Families for DCLRE1C Gene. Human Protein Atlas (HPA):. *Disease related genes ...
The gene responsible for A-T is called ATM, for Ataxia-Telangiectasia Mutated. The ATM gene produces a large protein that is ... ATAXIA-TELANGIECTASIA OVERVIEW. Howard M. Lederman and Thomas O. Crawford. Ataxia-telangiectasia (A-T) is a rare degenerative ... Scientists are intensively studying the ATM gene and protein, trying to learn more about what it does, how it does it, and why ... People with A-T have defective genes on both copies of chromosome 11 and therefore do not produce the protein. ...
Abbreviations: ATR, ataxia telangiectasia mutated- and Rad3-related; eRF, eukaryotic release factor; NMD, nonsense-mediated ... Search Tool for the Retrieval of Interacting Genes/Proteins; TERRA, telomeric repeat-containing RNA; UPF1, up-frameshift 1 ... UPF1 (up-frameshift 1) is a protein conserved in all eukaryotes that is necessary for NMD (nonsense-mediated mRNA decay). UPF1 ... Our bioinformatics survey of the interaction network of UPF1 with other human proteins, however, highlights that UPF1 also ...
Epidermal growth factor sensitizes cells to ionizing radiation by down-regulating protein mutated in ataxia-telangiectasia ... Cellular localization of the ataxia-telangiectasia-mutated (ATM) gene product and discrimination between mutated and normal ... The ataxia-telangiectasia gene product, a constitutively expressed nuclear protein that is not up-regulated following genome ... Analysis of the ATM protein in wild-type and ataxia telangiectasia cells. LAKIN N. D. ...
... showing that a prior exposure to a low dose of ionising radiation induces an adaptive response expressed as a reduction of gene ... 17699107 - Ataxia telangiectasia-mutated dependent dna damage checkpoint functions regulate gene e.... 17611227 - Helt ... 1614537 - Amplification of a gene encoding a p53-associated protein in human sarcomas.. 15298727 - Alterations of the p16ink4a/ ... There is some evidence that the protein kinase C-mediated signalling pathway is a key step for the transduction of the low-dose ...
... the protein encoded by the gene mutated in the radiosensitive syndrome ataxia-telangiectasia. Int. J. Radiat. Biol. 75: 1201- ... This pathway depends upon the presence of the protein products of the RAD52 epistasis group of genes. These proteins, which ... This is proved by the radiosensitive phenotype of the human syndrome ataxia telangiectasia, in which large defects in the ... In this regard, a lot of genes could be involved in the radiosensitive phenotype, only a few of which are known (Table II) and ...
... ataxia-telangiectasia; ATM and atm, mutated AT gene from human and mouse, respectively; ATM and Atm, AT protein from human and ... The gene mutated in AT was recently identified by positional cloning (8, 9). This gene, designated ATM, codes for a protein ... Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Ari Elson, Yaoqi Wang, Cathie J. Daugherty, Cynthia C. ... Pleiotropic defects in ataxia-telangiectasia protein-deficient mice. Ari Elson, Yaoqi Wang, Cathie J. Daugherty, Cynthia C. ...
AT stands for Ataxia-Telangiectasia. AT is defined as Ataxia-Telangiectasia very frequently. ... Comparison of ataxia-telangiectasia mutated protein expression in .... These conditions include molluscum, ataxia- ... The ataxia-telangiectasia mutated (ATM) gene encodes a nuclear 370-kd phosphoprotein known to be associated with chromosomal ... Blocking DNA repair protein likely to make cancer therapy safer. DIAGNOSIS Ataxia-telangiectasia DISCUSSION Ataxia- ...
ATR = ATAXIA TELANGIECTASIA-MUTATED AND RAD3-RELATED ATXR5 = ARABIDOPSIS TRITHORAX-RELATED PROTEIN 5 ... Identification of multiple proteins coupliing transcriptional gene-silencing to genome stability in Arabidopsis thaliana. PLoS ... Short-range interactions also occur between the 5′ and the 3′ end of genes, in particular in highly expressed genes . One ... As this association is more frequent in expressed genes, there is a possibility that different mechanisms for defining gene-TE ...
... proteins, disorders, pathways, orthologs, and expression. GeneCards - The Human Gene Compendium ... Protein Coding), X-Ray Repair Cross Complementing 5, including: function, ... KARP-1 is induced by DNA damage in a p53- and ataxia telangiectasia mutated-dependent fashion. (PMID: 9636207) Myung K. … ... Summaries for XRCC5 Gene Entrez Gene Summary for XRCC5 Gene. * The protein encoded by this gene is the 80-kilodalton subunit of ...
... ataxia telangiectasia-mutated), a 370-kDa protein kinase (58). The ATM gene is mutated in the human genetic disorder ataxia ... 2000) Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc. Natl. Acad. Sci. USA 97:10389-10394. ... 1999) The ataxia-telangiectasia related protein ATR mediates DNA-dependent phosphorylation of p53. Oncogene 18:3989-3995. ... 2000) Functional link of BRCA1 and ataxia telangiectasia gene product in DNA damage response. Nature 406:210-215. ...
Ataxia telangiectasia mutated. NM_000051. Gene Info. AURKAIP1. Aurora kinase A interacting protein 1. NM_017900. NM_001127229. ... TIMELESS interacting protein. NM_017858. Gene Info. TPR. Translocated promoter region, nuclear basket protein. NM_003292. Gene ... F-box protein 5. NM_001142522. NM_012177. Gene Info. FBXW7. F-box and WD repeat domain containing 7, E3 ubiquitin protein ... Charged multivesicular body protein 1A. NM_002768. NM_001083314. Gene Info. CLSPN. Claspin. NM_022111. NM_001190481. Gene Info ...
Ataxia Telangiectasia Mutated Proteins Human genes 0 description 1 * 108010004586 Ataxia Telangiectasia Mutated Proteins ...
Ataxia telangiectasia mutated homolog (human). NM_007499. Gene Info. Bmp4. Bone morphogenetic protein 4. NM_007554. Gene Info. ... F-box protein 5. NM_025995. Gene Info. Fbxw7. F-box and WD-40 domain protein 7. NM_001177773. NM_001177774. NM_080428. Gene ... RIKEN cDNA 5730590G19 gene. NM_029835. Gene Info. Apbb1. Amyloid beta (A4) precursor protein-binding, family B, member 1. NM_ ... MLX interacting protein-like. NM_021455. Gene Info. Mre11a. Meiotic recombination 11 homolog A (S. cerevisiae). NM_018736. Gene ...
KinaseImmunodeficiencyNeurodegenerativeCellsSuppressorApoptosisPhosphorylationPatients with ataxia-telangiectasiaAbstractPathwayDisorderResponse to DNA damageGenomeAntigenSusceptibilityDownstreamRadiationDefectsRecognizing abnormalChromosomeRegulationSinopulmonary infectionsAntibodyTarget genesEncodes a nuclearCellularIdentified genes that are differentially expressedMitochondrialTranscriptionOnset1995GeneticTranscriptionalAdaptorCharacteristicCodes for a proteinCellChromatinSyndromesTyrosineTelomereDifferentially expressed genesCancers
- At the cellular level, IR sensitivity and increased frequency of spontaneous and IR-induced chromosomal breakage and rearrangements are the hallmarks of A-T. The ATM gene, mutated in this syndrome, has been cloned and codes for a protein sharing homology with DNA-PKcs, a protein kinase involved in DNA double-strand break (DSB) repair and DNA damage responses. (elsevier.com)
- The characteristics of the A-T cellular phenotypes and ATM gene suggest that ATM may play a role similar to that of DNA-PKcs in DSB repair and that there is a primary DNA repair defect in A-T cells. (elsevier.com)
- Expression of the ATM protein in A-T cells corrected the defect in DSB repair in A-T nuclear extracts. (elsevier.com)
- One key protein that coordinates DNA repair with cell cycle progression and apoptosis is the tumor suppressor protein p53. (rupress.org)
- In vitro experiments demonstrated that downregulation of Ido1 in tumor cells was associated with decreased cell proliferation, increased apoptosis, and changed expression of cell cycle regulatory genes, whereas upregulation of Ido1 in the cells had the opposite effects. (hindawi.com)
- The protein encoded by this gene is a member of a family of proteins that inhibits apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. (antibodies-online.com)
- Particularly, ATM plays a primary role in transducing DSB signal to a broad spectrum of proteins involved in DNA repair, cell cycle checkpoints, and apoptosis (Shiloh, 2003 ). (pubmedcentralcanada.ca)
- in addition, induction of NF-κB target genes that counter apoptosis was impaired in Parp1 -/- MEFs. (sciencemag.org)
- miR-26a overexpression effectively reduced ATM expression, apoptosis, and apoptosis-related proteins in OGD-treated H9c2 cells. (bvsalud.org)
- Activated Akt targets downstream signaling substrates to regulate cell processes that are associated with tumor development, including regulators of apoptosis, gene transcription, cell cycle progression, and cellular metabolism (Figure 1). (thermofisher.com)
- The known up-regulated genes in the Rama 37-OPN library code for proteins with a variety of functions including those involved in metabolism, cell adhesion and migration, signal transduction and in apoptosis. (biomedcentral.com)
- BRCA1 is necessary for cellular processes ranging from cell cycle checkpoint control, DNA repair, regulation of transcription, protein ubiquitination, and apoptosis to chromatin remodeling ( 28 , 48 , 54 , 63 ). (asm.org)
- Tumor protein p53 is a nuclear transcription factor that regulates the expression of a wide variety of genes involved in apoptosis, growth arrest, or senescence in response to genotoxic or cellular stress. (thermofisher.com)
- p53 promotes apoptosis through multiple mechanisms, including transactivation of specific target genes, down-regulation of a distinct set of genes, and transcription-independent mechanisms [1, (thermofisher.com)
- This activates transcription of pro-apoptotic genes and renders cells susceptible to elimination via both apoptosis and natural killer cells. (pubfacts.com)
- Gene expression microarray data for 109 tumor cell lines with known sensitivity to the death ligand cytokine tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was used to identify genes with potential functional relationships determining responsiveness to TRAIL-induced apoptosis. (biomedcentral.com)
- IR induces rapid, de novo phosphorylation of endogenous p53 at two serine residues within the first 24 amino acids of the protein, one of which was identified as Ser 15 ( 7 , 8 ). (sciencemag.org)
- Phosphorylation of p53 at Ser 15 in response to DNA damage correlates with both the accumulation of total p53 protein as well as with the ability of p53 to transactivate downstream target genes in wild-type cells ( 8 ). (sciencemag.org)
- This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. (wikipedia.org)
- The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. (wikipedia.org)
- In this Perspective , we specifically highlight the role of sumoylation and ubiquitylation in ataxia-telangiectasia mutated (ATM) signaling in response to DNA double-strand breaks and hypothesize that ATM-induced phosphorylation is a unique node in regulating SUMO-targeted ubiquitylation in mammalian cells to combat DNA damage and to maintain genome integrity. (pubmedcentralcanada.ca)
- Phosphorylation of p56 chk1 did not occur when other checkpoint genes were inactive. (sciencemag.org)
- Life Technologies has developed a wide selection of Novex® primary antibodies, including phosphorylation site-specfic (phosphospecific) antibodies that allow you to analyze differential patterns of protein phosphorylation in the Akt pathway. (thermofisher.com)
- DSBs trigger a multitude of post-translational modifications that alter both, catalytic activities and the specificity of protein interactions including: phosphorylation, methylation, ubiquitylation, acetylation, and SUMOylation, followed by the turnaround of these changes as repair has been completed. (wikipathways.org)
- The BRCA1 protein becomes phosphorylated in response to DNA damage, but the effects of phosphorylation on recombinational repair are unknown. (asm.org)
- Recently, it has been shown that DNA damaging checkpoint proteins are activated by phosphorylation at the sites of DNA double strand breaks caused by ionizing radiation. (go.jp)
- Enhanced phosphorylation of transcription factor sp1 in response to herpes simplex virus type 1 infection is dependent on the ataxia telangiectasia-mutated protein. (pubfacts.com)
- In constitutive heterochromatin of mammals, DSB repair is delayed and relies on phosphorylation of the proteins HP1 and KAP1 by ATM [2, 8- (readbyqxmd.com)
- Treatment with prophylactic antibiotics or immune globulin may help patients with ataxia-telangiectasia. (merckmanuals.com)
- Thus, p56 chk1 appears to function downstream of several of the known Schizosaccharomyces pombe checkpoint gene products, including that encoded by rad3 + , a gene with sequence similarity to the ATM gene mutated in patients with ataxia telangiectasia. (sciencemag.org)
- An elevated alpha-fetoprotein level, present in almost all patients with ataxia-telangiectasia, often is associated with pathologic conditions of the liver and chronic hepatitis. (medscape.com)
- The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. (sciencemag.org)
- Parvovirus B19 NS1 protein induces cell cycle arrest at G2-phase by activating the ATR-CDC25C-CDK1 pathway. (sigmaaldrich.com)
- The resulting pairs of blunt phosphorylated signal ends (SEs) and hairpin-sealed coding ends (CEs) are processed and joined into a signal joint and coding joint, respectively, by proteins of the nonhomologous end-joining pathway of DNA DSB repair ( 5 ). (rupress.org)
- The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. (nih.gov)
- This is a prospective, open label, randomised, multi-centre Phase 2 study that will assess the efficacy and safety of olaparib monotherapy versus olaparib in combination with an inhibitor of ATR (AZD6738) and olaparib monotherapy versus olaparib in combination with an inhibitor of WEE1 (AZD1775) in second or third line setting in patients with TNBC prospectively stratified by presence/absence of qualifying tumour mutation in genes involved in the HRR pathway. (clinicaltrials.gov)
- During both the latent and the lytic cycle, KSHV is programmed to express genes which selectively modulate the DNA damage response (DDR) through the activation of the ataxia telangiectasia mutated (ATM) pathway and by phosphorylating factors associated with the DDR, including the major tumor suppressor protein p53 tumor suppressor p53. (mdpi.com)
- Explore and order pathway-specific siRNAs, real-time PCR assays, or optimized protein expression vectors. (qiagen.com)
- In addition to ABfinity™ antibodies, antibody pairs, and ELISA kits, we also offer Novex® multiplex assay panels for measuring the levels of total and phosphorylated proteins in the Akt pathway using the Luminex® platform. (thermofisher.com)
- The new Akt Pathway Total Magnetic 7-Plex and Phospho Magnetic 7-Plex Panels provide accurate quantitation of seven different proteins simultaneously in cell lysates and tissue homogenates (Figure 6). (thermofisher.com)
- To obtain a better understanding of this phenomenon and, in particular, the downstream target genes in the OPN signaling pathway, the technique of suppression subtractive hybridization (SSH) has been employed. (biomedcentral.com)
- An overview of this pathway and common sites where mutated upstream receptors and products of chromosomal translocation may activate the pathway is presented in Figure 1 . (nature.com)
- The pathway determining malignant cellular transformation, which depends upon mutation of the BRCA1 tumor suppressor gene, is poorly defined. (asm.org)
- Therefore, it is worthwhile to understand the accumulated data available describing the functioning of these proteins in various settings, in order to fully appreciate their relationship to the Hippo pathway. (pubmedcentralcanada.ca)
- Ataxia-telangiectasia (A-T) is a rare degenerative disorder that first becomes apparent during childhood. (atcp.org)
- Ataxia-telangiectasia (AT) is a human autosomal recessive disorder characterized by a wide variety of progressive clinical symptoms (for review, see ref. 1 ). (pnas.org)
- The ATM gene is mutated in the human genetic disorder ataxia telangiectasia ( 58 ). (asm.org)
- Ataxia-telangiectasia is an autosomal-recessive primary immunodeficiency disorder that involves combined humoral and cellular deficiencies . (merckmanuals.com)
- Ataxia-Telangiectasia or A-T, is a rare and complex genetic disorder. (atsociety.org.uk)
- For example, Fanconi's anemia, a disorder where individuals are prone to development of myeloid leukemias, results from inheritance of one of several different mutated genes involved in repair of DNA cross-links. (aacrjournals.org)
- Ataxia telangiectasia (AT) is a rare human autosomal recessive disorder with pleiotropic phenotypes, including neuronal degeneration, immune dysfunction, premature ageing and increased cancer risk. (uptodate.com)
- Ataxia-telangiectasia (A-T), also called Louis-Bar syndrome, is a rare, genetic neurological disorder of childhood that progressively destroys part of the motor control area of the brain, leading to a lack of balance and coordination. (thefreedictionary.com)
- Ataxia Telangiectasia (AT) is a rare and progressive genetic disorder characterized by primary immunodeficiency and a resultant degradation of the nervous system. (cags.org.ae)
- ATM protein, which is the product of the gene mutated in radiation sensitive disorder called ataxia-telangiectasia (AT), functions as the primary sensor for DNA double strand breaks, and when visualized with an antibody recognizing phosphorylated ATM at S1981, phosphorylated ATM appears as nuclear foci after irradiation. (go.jp)
- Response to DNA damage is detected by the ataxia-telangiectasia mutated (ATM) (reviewed in refs. (pnas.org)
- The protein also functions in the regulation of the cell cycle in response to DNA damage. (genecards.org)
- In response to DNA damage, cells with wild-type ATM accumulate p53 protein and show a subsequent increase in p53 activity, whereas cells with defective ATM show a smaller increase in the amount of p53 protein in response to IR ( 4 , 6 ). (sciencemag.org)
- However, the induction of Wip1 proteins seems to have a delayed onset in contrast to an immediate induction of the WIP1 transcripts in response to DNA damage. (aacrjournals.org)
- The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. (wikipedia.org)
- DNA repair syndromes are heterogeneous disorders caused by pathogenic variants in genes encoding proteins key in DNA replication and/or the cellular response to DNA damage. (aacrjournals.org)
- The finding, published online in Nature Cell Biology, illuminates a connection between proteins involved in neurodegenerative disease and in cells' response to DNA damage. (emory.edu)
- This protein and ATM share similarity with Schizosaccharomyces pombe rad3, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. (origene.com)
- In response to DNA damage, Chk1 and Chk2, activated by ATR (Ataxia-Telangiectasia and Rad3 Related) and ATM Ataxia Telangiectasia Mutated Gene), respectively, phosphorylate p53. (thermofisher.com)
- Another apoptotic gene, PERP, is induced in response to DNA damage. (thermofisher.com)
- Bloom syndrome and ataxia-telangiectasia are autosomal recessive human disorders characterized by immunodeficiency, genome instability and predisposition to develop cancer. (nii.ac.jp)
- Importantly, these chromatin domains, which were scattered along the genome, represented active and repressed genes in euchromatin, silent heterochromatin, and intergenic regions. (biomedcentral.com)
- We are particularly interested in understanding how DNA damage is identified and resolved during DNA replication, when the genome is particularly vulnerable due to stalling of the replication fork at naturally arising and induced DNA lesions, structures or protein-DNA complexes. (stanford.edu)
- New Pathways for Genome Stability/Human Disease: Recently, we performed a genome-wide siRNA screen to define the processes and proteins that protect cells from DNA damage, particularly during DNA replication. (stanford.edu)
- We are currently characterizing proteins identified in this screen with interesting ties to genome maintenance and human disease. (stanford.edu)
- Perhaps the best that can be said is that the repertoire of proteins inferred from the genome sequence establishes beyond a doubt that S. cerevisiae is a bone fide eukaryote. (asm.org)
- Finally, many of the genes from the endosymbiont were either lost or incorporated into the nuclear genome. (asm.org)
- We recently developed a novel system to create DNA DSBs at defined endogenous sites in the human genome and used this system to detect protein recruitment and loss at and around these breaks by chromatin immunoprecipitation. (aacrjournals.org)
- ATM is thought to be a master controller of cell cycle checkpoint signalling pathways that are required for cellular responses to DNA damage such as double-strand breaks that are induced by ionizing radiation and complexes with BRCA1 in the multi-protein complex BASC (BRAC1-associated genome surveillance complex). (nih.gov)
- A new Tel Aviv University study identifies elevated levels of a protein called ubiquilin-4 as a new biomarker for genome instability. (medicalxpress.com)
- The response is composed of a broad, fine-tuned signaling network involving a standing army of proteins fully dedicated to this mission, as well as reserve proteins recruited temporarily to help resolve genome integrity. (medicalxpress.com)
- In 1995, the Shiloh lab discovered the gene encoding of one of the major sentries at the gate of genome stability-the protein ataxia-telangiectasia mutated (ATM). (medicalxpress.com)
- It concluded a long effort to identify the gene mutated in a severe genome instability syndrome, ataxia-telangiectasia (A-T). (medicalxpress.com)
- Gene expression relies on dynamic interplay among cis elements, chromatin domains, and genome architecture. (upenn.edu)
- The latter is of intense interest as ~10% of human diseases may arise from defects in genome topology that impact gene transcription. (upenn.edu)
- Foundational questions remain about mechanisms of genome architecture reorganization and its impact on gene expression during cellular differentiation. (upenn.edu)
- Owing to its high sensitivity and full coverage of the human genome, transcriptomics is one of the most widely applied tools for biomarker research by selecting genes that are differentially expressed in the majority of the samples, or in a specific subgroup. (biomedcentral.com)
- Required for V(D)J recombination, the process by which exons encoding the antigen-binding domains of immunoglobulins and T-cell receptor proteins are assembled from individual V, (D), and J gene segments. (genecards.org)
- We demonstrate that there is an increase in the accumulation of unrepaired coding ends during different steps of antigen receptor gene assembly at both the immunoglobulin and T cell receptor loci in developing ATM-deficient B and T lymphocytes. (rupress.org)
- The exons encoding the variable region of lymphocyte antigen receptor chains are assembled from V, J, and in some cases D gene segments through the process of V(D)J recombination ( 1 ). (rupress.org)
- Most lymphoid malignancies in A-T patients have karyotypic abnormalities with chromosome breakpoints clustering near antigen receptor genes ( 11 ). (rupress.org)
- Collectively, these findings suggest that ATM functions during antigen receptor gene assembly. (rupress.org)
- However, mice deficient in either p53 or Chk2 are not lymphopenic and are not prone to lymphoid tumors with antigen receptor gene translocations, as are ATM-deficient mice ( 24 , 25 ). (rupress.org)
- Antibody - Any of a large number of proteins produced by specialized blood cells after stimulation by an antigen and that act specifically against the antigen in an immune response. (thefreedictionary.com)
- Innate lymphocytes express invariant germline-encoded antigen receptors, while adaptive lymphocytes express diverse antigen receptors somatically-assembled from recombination of germline variable (V), diversity (D), and joining (J) gene segments. (upenn.edu)
- Developing B and T cells share developmental strategies that include mono-allelic gene recombination and feedback mechanisms, which link antigen protein expression from functional V(D)J rearrangements to further developmental progression or negative selection of auto-reactive cells. (upenn.edu)
- In the past few years, we have discovered that RAG DSBs activate tissue-specific DNA damage responses and transcend hazardous intermediates during antigen receptor gene assembly. (upenn.edu)
- Also, reduced androgen receptor, prostate particular antigen, p53 and p21 proteins levels were confirmed in response to treatment with NU9056. (cylch.org)
- 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)
- The breast/ovarian cancer susceptibility gene BRCA1 exerts its tumor suppressor function, at least in part, by participating in DNA repair and/or DNA damage-responsive pathways. (aacrjournals.org)
- Since nasal secretions are associated with antiviral activity and are deficient in ataxia-telangiectasia, there appears to be a causal relationship to the susceptibility for respiratory infection observed in ataxia-telangiectasia. (medscape.com)
- Further analyses showed a pronounced induction of ATM also at the protein level, and the phosphorylations of ATM and its downstream target, Chk2. (uio.no)
- In doing so, it activates expression of downstream genes leading to programmed cell death and/or cell cycle arrest, thus functioning as a tumor suppressor. (thermofisher.com)
- This is defined as the transfer of phosphoryl groups [(PO3)2-] from one molecule to another, and serves as a transfer of energy that results in the activation, or deactivation of downstream proteins. (biolegend.com)
- Cells without any functional ATM protein are hypersensitive to radiation and do not respond normally to DNA damage. (medlineplus.gov)
- Radiosensitivity in ataxia-telangiectasia : anomalies in radiation-induced cell cycle delay. (nii.ac.jp)
- The work provides new insights into mechanisms of how the body fixes environmentally induced DNA damage and into the deadly neurological disease ataxia-telangiectasia (A-T), said senior author Christopher Bakkenist, assistant professor of radiation oncology, pharmacology and chemical biology at UPCI and the School of Medicine. (acronymfinder.com)
- Its cognate gene, ATM (see below), is mutated in ataxia telangiectasia, a rare neurodegenerative disease characterised by ataxia telangiectasias, increased chromosome fragility when exposed to ionising radiation and predisposition to lymphomas. (thefreedictionary.com)
- We show that Granta-519 and UPN2 cells have low levels of ATM protein, are defective in DNA damage-induced ATM-dependent signaling, are radiation sensitive, and have cell cycle checkpoint defects: all characteristics of defective ATM function. (aacrjournals.org)
- Ataxia telangiectasia (A-T) patients are extremely sensitive to ionizing radiation, such as X- and γ-rays (Lavin, 2008 ). (pubmedcentralcanada.ca)
- Tumors with high levels of ubiquilin-4 may be more resistant to radiation and some chemotherapies than those with normal levels of this protein. (medicalxpress.com)
- Cell lines derived from A-T patients exhibit hypersensitivity to IR and defects in several IR-inducible cell-cycle checkpoints, including a diminished irradiation-induced arrest in the G 1 phase of the cell-cycle mediated by the p53 tumor suppressor gene product ( 4 , 5 ). (sciencemag.org)
- Specifically, we found that defects in some RNA processing genes lead to DNA damage through the formation of toxic RNA-DNA hybrids and R-loops. (stanford.edu)
- Ataxia-telangiectasia mutated (ATM)-deficient lymphocytes exhibit defects in coding joint formation during V(D)J recombination in vitro. (rupress.org)
- However, whether this approach is applicable to other human cancers with defects in other DNA repair genes has yet to be determined. (aacrjournals.org)
- A-T is caused by defects in Ataxia-Telagiectasia Mutated (Atm) gene. (unina.it)
- Ataxia-telangiectasia is associated with glucose intolerance and insulin resistance probably due to defects in the affinity of the receptors for insulin. (medscape.com)
- Phenotypic characterization of uvsB mutants shows that they possess defects in additional aspects of the DNA damage response besides checkpoint control, including inhibition of septum formation, regulation of gene expression, and induced mutagenesis. (genetics.org)
- ATM gene located on chromosome 11q22-23 spanning over 160 kb of genomic DNA and produces an approximately 350 kDa protein that plays a key role in DNA damage response, especially for double-strand break [ 19 ]. (hindawi.com)
- Thymocytes from ATM-deficient mice have an increased frequency of biallelic loss of distal Vα gene segments, and 11% of nontransformed αβ T cells in these mice have karyotypic abnormalities involving chromosome 14, which contains the TCRα/δ locus ( 17 , 18 ). (rupress.org)
- More than half of all bladder tumors (all grades and stages) contain chromosome 9 alterations suggesting that chromosome 9 genes may be involved in early tumor development. (frontiersin.org)
- In vertebrate cells, the elimination of DSBs with minimal nucleotide sequence change involves the spatiotemporal orchestration of an apparently endless number of proteins ranging, according to their action, from the nucleotide level to nucleosome organization and chromosome architecture. (wikipathways.org)
- Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. (cancerindex.org)
- A better understanding of the basic regulatory processes that control cancer metabolism is critical for eventually targeting this process for the development of novel cancer therapeutics," said Rugang Zhang Ph.D., associate professor in Wistar's Gene Expression and Regulation Program and corresponding author of the study. (medicalxpress.com)
- PERP is a putative tetraspan transmembrane protein that represents a new member of the PMP-22/Gas family of proteins implicated in cell growth regulation. (thermofisher.com)
- Gene co-regulation and statistical interaction was assessed with q-order partial correlation analysis and non-rejection rate. (biomedcentral.com)
- a-synuclein may be involved in the regulation of dopamine release and transport and also may function to induce fibrillization of microtubule-associated protein tau. (biolegend.com)
- ATM Antibody AP08052PU detects endogenous levels of total ATM protein. (antibodies-online.com)
- Immunological abnormalities in ataxia-telangiectasia include the following: decreased peripheral lymphoid tissue, stunted growth, lymphopenia, absence of delayed hypersensitivity, impaired skin homograft rejection, impaired circulating antibody response to some (weak) antigens, and impaired T-cell function. (medscape.com)
- Ataxia-telangiectasia involves combined humoral and cellular deficiencies. (merckmanuals.com)
- Although sumoylation and ubiquitylation have distinct functions, they are often tightly associated with each other to fine-tune protein fate in transducing signals to regulate a wide variety of cellular functions, including DNA damage response, cell proliferation, DNA replication, embryonic development, and cell differentiation. (pubmedcentralcanada.ca)
- The symptoms associated with A-T reflect the main role of the AT gene, which is to induce several cellular responses to DNA damage, such as preventing damaged DNA from being reproduced. (thefreedictionary.com)
- Mutant forms of this gene result in non-functional protein, which cause cellular death, especially in the cerebellum. (cags.org.ae)
- The genes in the panel are co-regulated and at least 40% of them functionally interact in signal transduction pathways that regulate cell death and cell survival, cellular differentiation and morphogenesis. (biomedcentral.com)
- Since that time many cellular features have been discovered to utilize this protein. (cylch.org)
- Moreover, HCV affects the steady-state levels of a mitochondrial protein chaperone known as prohibitin, leading to impaired function of the mitochondrial respiratory chain with the overproduction of ROS [ 9 ]. (mdpi.com)
- If these nuclear genes that encode mitochondrial proteins were once confined to an endosymbiont, how did they get out of the mitochondrion and enter the nucleus? (asm.org)
- This gene encodes an integral outer mitochondrial membrane protein that blocks the apoptotic death of some cells such as lymphocytes. (antibodies-online.com)
- The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (VDAC) opening. (antibodies-online.com)
- In the present study, an extracellular copper-zinc superoxide dismutase (ecCuZnSOD) gene and a mitochondrial manganese superoxide dismutase (mtMnSOD) gene were cloned from hemocytes of red claw crayfish, Cherax quadricarinatus. (jove.com)
- Ataxia-telangiectasia mutated (ATM) also can activate transcription of secondary molecules including p53, which regulate genes including p21Cip/Waf-1 and 14-3-3 σ (reviewed in refs. (pnas.org)
- GO annotations related to this gene include poly(A) RNA binding and transcription regulatory region DNA binding . (genecards.org)
- This protein belongs to the basic helix-loop-helix family of transcription factors. (cancerindex.org)
- It is a transcriptional repressor of genes that require a bHLH protein for their transcription. (cancerindex.org)
- These transcription factors will lead to the activation of various genes, which contributes to the proliferative and anti-apoptotic effects that are common drivers of cancer progression [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. (pubmedcentralcanada.ca)
- The protein encoded by this gene is a member of the STAT family of transcription factors. (novusbio.com)
- Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. (medlineplus.gov)
- How are genetic conditions and genes named? (nih.gov)
- The genetic hallmark of MCL is a chromosomal translocation t(11;14)(q13;q32) that juxtaposes IgH gene promoter elements upstream of CCND1 ( 15 ). (aacrjournals.org)
- The tumor suppressor p53 binding protein 1 (53BP1) binds to the DNA-binding domain of p53 and enhances p53-mediated transcriptional activation. (rupress.org)
- Moreover, we studied the transcriptional targets in these cells in response to cisplatin, particularly the expression profiles of genes associated with DNA damage response. (uio.no)
- Acetylation outcomes in an open up chromatin structure by detatching positive fees from histones, hence inducing proteins conformational changes, that allows transcriptional equipment to gain access to the DNA and promote transcriptional activity. (cylch.org)
- AR acetylation is usually considered to regulate the recruitment of co-activators towards the transcriptional equipment of androgen reactive genes . (cylch.org)
- In particular, he has conducted research on signals and adaptor proteins that mediate protein sorting in the endosomal-lysosomal system. (asbmb.org)
- This caspase cascade is triggered when initiator procaspases (e.g. procaspases 8, 9, 10) are aggregated with the help of adaptor proteins, thus facilitating mutual activation due to low protease activity or conformational changes of the procaspases. (antibodies-online.com)
- The 14-3-3 proteins are a family of conserved adaptor and scaffolding proteins expressed in all eukaryotic cells. (qiagen.com)
- Research suggests that people who carry one mutated copy of the ATM gene in each cell may have an increased risk of developing several other types of cancer. (medlineplus.gov)
- E) Immunohistochemistry of ATM protein in gastric cancer cell-lines. (cdc.gov)
- Knockdown of autophagy-related gene 5 inhibited basal autophagy and diminished oxidative stress-induced autophagy and cell death. (biomedsearch.com)
- We have isolated an anti-proliferative cell cycle regulator named G2A (for G 2 accumulation), which is predominantly expressed in immature T and B lymphocyte progenitors and is a member of the seven membrane-spanning G protein-coupled receptor family. (pnas.org)
- Consistent with an oncogenic function, the WIP1 gene is present in amplified copy numbers and is overexpressed in many human cancer types, including breast carcinomas, ovarian clear cell adenocarcinomas, neuroblastomas, pancreatic adenocarcinomas, gastric carcinomas, and medulloblastomas ( 10 - 16 ). (aacrjournals.org)
- We presented that the level of miR-16 is rapidly induced on DNA damage stress, which postpones the accumulation of the Wip1 protein and thus allows cells to initiate functional cell cycle checkpoints in the early stage of DNA damage response. (aacrjournals.org)
- Fluorescence-activated cell sorting (FACS) analysis confirmed ∼85% and ∼83% of CMs differentiated from ESCs and iPSCs, respectively, were positive for cardiac troponin T. At a single-cell level, both cell types displayed similar calcium handling and electrophysiological properties, with gene expression comparable to the human fetal heart marked by striated sarcomeres. (stanford.edu)
- Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene. (wikipedia.org)
- Despite reduced levels of several NER proteins in the testis cancer cell lines, a proficient removal of UVC-induced DNA lesions by NER was observed using an alkaline comet assay. (uio.no)
- Required for protein stability of MTOR and MTOR-related proteins, and cell cycle progress by growth factors (PubMed:25657994). (nih.gov)
- The ataxia telangiectasia mutated ( ATM ) gene is altered in several human cancers including mantle cell lymphoma (MCL). (aacrjournals.org)
- When the AT gene is mutated into ATM, the signaling networks are affected and the cell no longer responds correctly to minimize the damage. (thefreedictionary.com)
- The root cause of A-T-associated ataxia is cell death in the brain, specifically the large branching cells of the nervous system (Purkinje's cells) which are located in the cerebellum. (thefreedictionary.com)
- In this study, we have utilized suppressive subtractive hybridization (SSH) to evaluate OPN regulated gene expression, using the Rama 37 benign non-invasive rat mammary cell line and a subclone, Rama 37-OPN. (biomedcentral.com)
- Four of the most differentially expressed genes between the benign and in vitro malignant rat mammary cell lines are tumor protein translationally controlled I (TPTI), aryl hydrocarbon receptor nuclear translocator (ARNT), ataxia telangiectasia mutated (ATM) and RAN GTPase (RAN). (biomedcentral.com)
- SSH has been used in the present study to determine differential gene expression between the benign rat mammary cell line Rama 37 (R37) and R37 cells stably transfected with an expression vector for OPN, termed R37-OPN cells. (biomedcentral.com)
- Some of the differentially expressed genes were then tested further by Real Time PCR for the relative level of their expressed mRNAs in a series of cell lines established from human breast cancer and the mRNA species which changes the most has been identified as RAN GTPase. (biomedcentral.com)
- The production of DSBs can be quantified by biochemical techniques, e.g., pulsed field gel electrophoresis (PFGE) and cell imaging, either globally or damage specific, through immunostaining of marker proteins or recruitment of fluorescent proteins to the DNA breaks. (wikipathways.org)
- RAG1/RAG2 (RAG) endonuclease-mediated assembly of immunoglobulin (Ig) and T cell receptor (TCR) genes in immature B and T lymphocytes, respectively, is essential for the development and function of adaptive immunity. (upenn.edu)
- The advantage of co-acting gene clusters is that this analysis does not depend on differential expression and is able to incorporate direct- and indirect gene interactions as well as tissue- and cell-specific characteristics. (biomedcentral.com)
- This approach (1) identified a descriptor of TRAIL sensitivity which performs significantly better as a predictor of TRAIL sensitivity than any previously reported gene signatures, (2) identified potential novel regulators of TRAIL-responsiveness and (3) provided a systematic view highlighting fundamental differences between the molecular wiring of sensitive and resistant cell types. (biomedcentral.com)
- Full length human recombinant protein of human TP53 (NP_000537) produced in HEK293T cell. (novusbio.com)
- Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. (novusbio.com)
- Hence, proteins acetylation and deacetylation can possess significant results on cell function, as well as for cells to keep normal development and differentiation it's important these two features maintain equilibrium. (cylch.org)
- However, the substrate for these processes is not the naked DNA molecule, but chromatin, a highly structured and dynamic macromolecular entity formed by the association of genomic DNA with histones and non-histone proteins. (biomedcentral.com)
- This protein binds to chromatin prior to DNA damage and is phosphorylated by ATR after the damage. (wikipedia.org)
- Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT , TERC , RTEL1 , CTC1 and ACD . (springer.com)
- Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed. (springer.com)
- Identification of differentially expressed genes from transcriptomic studies is one of the most common mechanisms to identify tumor biomarkers. (biomedcentral.com)
- The machine learning technique Random Forest in the statistical environment "R" with backward elimination was used to identify the key predictors of TRAIL sensitivity and differentially expressed genes were identified using the software GeneSpring. (biomedcentral.com)