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Ataxia TelangiectasiaAtaxia Telangiectasia Mutated ProteinsTelangiectasisTelangiectasia, Hereditary HemorrhagicAtaxiaTumor Suppressor ProteinsCerebellar AtaxiaCell Cycle ProteinsProtein-Serine-Threonine KinasesRetinal TelangiectasisFriedreich AtaxiaDNA-Binding ProteinsDNA DamageSpinocerebellar AtaxiasRadiation, IonizingCheckpoint Kinase 2DNA RepairGait AtaxiaGamma RaysRadiation ToleranceTumor Suppressor Protein p53DNA Breaks, Double-StrandedDNA-Activated Protein KinaseEpistaxisPhosphorylationPyronesActivin Receptors, Type IIArteriovenous MalformationsHistonesNuclear ProteinsFibroblastsMutationDose-Response Relationship, RadiationCell CycleNijmegen Breakage SyndromeStreptonigrinCREST SyndromeCell LineProtein KinasesSignal TransductionG2 PhaseDNA ReplicationChromosome BreakageMicrocephalyUltraviolet RaysHeterozygoteX-RaysChromosome AberrationsApoptosisInfrared RaysGenes, cdcNucleic Acid Synthesis InhibitorsReplication Protein ACell Line, TumorS PhaseCell Line, TransformedDNA Repair EnzymesGenomic InstabilityCell SurvivalCells, CulturedLymphocytesG2 Phase Cell Cycle CheckpointsTelomereAphidicolinTelomeric Repeat Binding Protein 2Mice, KnockoutIron-Binding ProteinsCell Cycle CheckpointsDNAPhenotypeCardiac Output, HighHydroxyureaActivin Receptors, Type IMorpholinesMutation, MissenseComet AssayHeLa CellsChromosome DisordersHomozygoteBleomycinCaffeineAlkylating AgentsCerebellumChromosomes, Human, Pair 11SerineProteinsSyndromeImmunologic Deficiency SyndromesIntracellular Signaling Peptides and ProteinsRNA, Small InterferingMolecular Sequence DataDNA LigasesCell AgingG1 PhaseMice, 129 StrainRNA InterferenceBase SequencePedigreeChromosomal Proteins, Non-HistoneCell NucleusChromosomes, Human, Pair 14BRCA1 ProteinMachado-Joseph DiseaseCyclin-Dependent Kinase Inhibitor p21Oxidative StressChromatinEnzyme ActivationDNA Mutational AnalysisImmunoblottingRetinal DiseasesRecombination, GeneticHCT116 CellsCamptothecinPoly(ADP-ribose) PolymerasesLymphomaBlotting, WesternGene Rearrangement, T-LymphocyteChromosomal InstabilityLeucine ZippersAngiodysplasiaTrinucleotide Repeat Expansioncdc25 PhosphatasesPhosphatidylinositol 3-KinasesTopoisomerase I InhibitorsTranslocation, GeneticModels, BiologicalKaryotypingRadiation-Sensitizing AgentsThreonineMitosisIntracranial Arteriovenous MalformationsProto-Oncogene Proteins c-ablAndrostadienesFlow CytometryProto-Oncogene Proteins c-mdm2Enzyme InhibitorsCell DivisionAllelesProtein BindingGene DeletionTelomeraseMice, Mutant StrainsDown-Regulation
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 6.5.1.1 (ATP) and EC 6.5.1.2 (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.

p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. (1/2256)

Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.  (+info)

Requirement of ATM in phosphorylation of the human p53 protein at serine 15 following DNA double-strand breaks. (2/2256)

Microinjection of the restriction endonuclease HaeIII, which causes DNA double-strand breaks with blunt ends, induces nuclear accumulation of p53 protein in normal and xeroderma pigmentosum (XP) primary fibroblasts. In contrast, this induction of p53 accumulation is not observed in ataxia telangiectasia (AT) fibroblasts. HaeIII-induced p53 protein in normal fibroblasts is phosphorylated at serine 15, as determined by immunostaining with an antibody specific for phosphorylated serine 15 of p53. This phosphorylation correlates well with p53 accumulation. Treatment with lactacystin (an inhibitor of the proteasome) or heat shock leads to similar levels of p53 accumulation in normal and AT fibroblasts, but the p53 protein lacks a phosphorylated serine 15. Following microinjection of HaeIII into lactacystin-treated normal fibroblasts, lactacystin-induced p53 protein is phosphorylated at serine 15 and stabilized even in the presence of cycloheximide. However, neither stabilization nor phosphorylation at serine 15 is observed in AT fibroblasts under the same conditions. These results indicate the significance of serine 15 phosphorylation for p53 stabilization after DNA double-strand breaks and an absolute requirement for ATM in this phosphorylation process.  (+info)

Atm is dispensable for p53 apoptosis and tumor suppression triggered by cell cycle dysfunction. (3/2256)

Both p53 and ATM are checkpoint regulators with roles in genetic stabilization and cancer susceptibility. ATM appears to function in the same DNA damage checkpoint pathway as p53. However, ATM's role in p53-dependent apoptosis and tumor suppression in response to cell cycle dysregulation is unknown. In this study, we tested the role of murine ataxia telangiectasia protein (Atm) in a transgenic mouse brain tumor model in which p53-mediated apoptosis results in tumor suppression. These p53-mediated activities are induced by tissue-specific inactivation of pRb family proteins by a truncated simian virus 40 large T antigen in brain epithelium. We show that p53-dependent apoptosis, transactivation, and tumor suppression are unaffected by Atm deficiency, suggesting that signaling in the DNA damage pathway is distinct from that in the oncogene-induced pathway. In addition, we show that Atm deficiency has no overall effect on tumor growth and progression in this model.  (+info)

GADD45 induction of a G2/M cell cycle checkpoint. (4/2256)

G1/S and G2/M cell cycle checkpoints maintain genomic stability in eukaryotes in response to genotoxic stress. We report here both genetic and functional evidence of a Gadd45-mediated G2/M checkpoint in human and murine cells. Increased expression of Gadd45 via microinjection of an expression vector into primary human fibroblasts arrests the cells at the G2/M boundary with a phenotype of MPM2 immunopositivity, 4n DNA content and, in 15% of the cells, centrosome separation. The Gadd45-mediated G2/M arrest depends on wild-type p53, because no arrest was observed either in p53-null Li-Fraumeni fibroblasts or in normal fibroblasts coexpressed with p53 mutants. Increased expression of cyclin B1 and Cdc25C inhibited the Gadd45-mediated G2/M arrest in human fibroblasts, indicating that the mechanism of Gadd45-mediated G2/M checkpoint is at least in part through modulation of the activity of the G2-specific kinase, cyclin B1/p34(cdc2). Genetic and physiological evidence of a Gadd45-mediated G2/M checkpoint was obtained by using GADD45-deficient human or murine cells. Human cells with endogenous Gadd45 expression reduced by antisense GADD45 expression have an impaired G2/M checkpoint after exposure to either ultraviolet radiation or methyl methanesulfonate but are still able to undergo G2 arrest after ionizing radiation. Lymphocytes from gadd45-knockout mice (gadd45 -/-) also retained a G2/M checkpoint initiated by ionizing radiation and failed to arrest at G2/M after exposure to ultraviolet radiation. Therefore, the mammalian genome is protected by a multiplicity of G2/M checkpoints in response to specific types of DNA damage.  (+info)

A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. (5/2256)

Checkpoints maintain the order and fidelity of the eukaryotic cell cycle, and defects in checkpoints contribute to genetic instability and cancer. Much of our current understanding of checkpoints comes from genetic studies conducted in yeast. In the fission yeast Schizosaccharomyces pombe (Sp), SpRad3 is an essential component of both the DNA damage and DNA replication checkpoints. The SpChk1 and SpCds1 protein kinases function downstream of SpRad3. SpChk1 is an effector of the DNA damage checkpoint and, in the absence of SpCds1, serves an essential function in the DNA replication checkpoint. SpCds1 functions in the DNA replication checkpoint and in the S phase DNA damage checkpoint. Human homologs of both SpRad3 and SpChk1 but not SpCds1 have been identified. Here we report the identification of a human cDNA encoding a protein (designated HuCds1) that shares sequence, structural, and functional similarity to SpCds1. HuCds1 was modified by phosphorylation and activated in response to ionizing radiation. It was also modified in response to hydroxyurea treatment. Functional ATM protein was required for HuCds1 modification after ionizing radiation but not after hydroxyurea treatment. Like its fission yeast counterpart, human Cds1 phosphorylated Cdc25C to promote the binding of 14-3-3 proteins. These findings suggest that the checkpoint function of HuCds1 is conserved in yeast and mammals.  (+info)

Risk of breast cancer and other cancers in heterozygotes for ataxia-telangiectasia. (6/2256)

Mortality from cancer among 178 parents and 236 grandparents of 95 British patients with ataxia-telangiectasia was examined. For neither parents nor grandparents was mortality from all causes or from cancer appreciably elevated over that of the national population. Among mothers, three deaths from breast cancer gave rise to a standardized mortality ratio of 3.37 (95% confidence interval (CI): 0.69-9.84). In contrast, there was no excess of breast cancer in grandmothers, the standardized mortality ratio being 0.89 (95% CI: 0.18-2.59), based on three deaths. This is the largest study of families of ataxia-telangiectasia patients conducted in Britain but, nonetheless, the study is small and CIs are wide. However, taken together with data from other countries, an increased risk of breast cancer among female heterozygotes is still apparent, though lower than previously thought.  (+info)

The Drosophila ATM homologue Mei-41 has an essential checkpoint function at the midblastula transition. (7/2256)

BACKGROUND: Drosophila embryogenesis is initiated by 13 rapid syncytial mitotic divisions that do not require zygotic gene activity. This maternally directed cleavage phase of development terminates at the midblastula transition (MBT), at which point the cell cycle slows dramatically, membranes surround the cortical nuclei to form a cellular blastoderm, and zygotic gene expression is first required. RESULTS: We show that embryos lacking Mei-41, a Drosophila homologue of the ATM tumor suppressor, proceed through unusually short syncytial mitoses, fail to terminate syncytial division following mitosis 13, and degenerate without forming cells. A similar cleavage-stage arrest is produced by mutations in grapes, which encodes a homologue of the Checkpoint-1 kinase. We present biochemical, cytological and genetic data indicating that Mei-41 and Grapes are components of a conserved DNA-replication/damage checkpoint pathway that triggers inhibitory phosphorylation of the Cdc2 kinase and mediates resistance to replication inhibitors and DNA-damaging agents. This pathway is nonessential during postembryonic development, but it is required to terminate the cleavage stage at the MBT. Cyclins are required for Cdc2 kinase activity, and mutations in cyclin A and cyclin B bypass the requirement for mei-41 at the MBT. These mutations do not restore wild-type syncytial cell-cycle timing or the embryonic replication checkpoint, however, suggesting that Mei-41-mediated inhibition of Cdc2 has an additional essential function at the MBT. CONCLUSIONS: The Drosophila DNA-replication/damage checkpoint pathway can be activated by externally triggered DNA damage or replication defects throughout the life cycle, and under laboratory conditions this inducible function is nonessential. During early embryogenesis, however, this pathway is activated by developmental cues and is required for the transition from maternal to zygotic control of development at the MBT.  (+info)

Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. (8/2256)

Cells from individuals with the recessive cancer-prone disorder ataxia telangiectasia (A-T) are hypersensitive to ionizing radiation (I-R). ATM (mutated in A-T) is a protein kinase whose activity is stimulated by I-R. c-Abl, a nonreceptor tyrosine kinase, interacts with ATM and is activated by ATM following I-R. Rad51 is a homologue of bacterial RecA protein required for DNA recombination and repair. Here we demonstrate that there is an I-R-induced Rad51 tyrosine phosphorylation, and this induction is dependent on both ATM and c-Abl. ATM, c-Abl, and Rad51 can be co-immunoprecipitated from cell extracts. Consistent with the physical interaction, c-Abl phosphorylates Rad51 in vitro and in vivo. In assays using purified components, phosphorylation of Rad51 by c-Abl enhances complex formation between Rad51 and Rad52, which cooperates with Rad51 in recombination and repair. After I-R, an increase in association between Rad51 and Rad52 occurs in wild-type cells but not in cells with mutations that compromise ATM or c-Abl. Our data suggest signaling mediated through ATM, and c-Abl is required for the correct post-translational modification of Rad51, which is critical for the assembly of Rad51 repair protein complex following I-R.  (+info)

ATM-dependent phosphorylation of ATF2 is required for the DNA damage response.ATM-dependent phosphorylation of ATF2 is required for the DNA damage response.
Activating transcription factor 2 (ATF2) is regulated by JNK/p38 in response to stress. Here, we demonstrate that the protein kinase ATM phosphorylates ATF2 on serines 490 and 498 following ionizing radiation (IR). Phosphoantibodies to ATF2(490/8) reveal dose- and time-dependent phosphorylation of ATF2 by ATM that results in its rapid colocalization with gamma-H2AX and MRN components into IR-induced foci (IRIF). Inhibition of ATF2 expression decreased recruitment of Mre11 to IRIF, abrogated S phase checkpoint, reduced activation of ATM, Chk1, and Chk2, and impaired radioresistance. ATF2 requires neither JNK/p38 nor its DNA binding domain for recruitment to IRIF and the S phase checkpoint. Our findings identify a role for ATF2 in the DNA damage response that is uncoupled from its transcriptional activity. ...
Targeted Mutations in the ATR Pathway Define Agent-Specific Requirements for Cancer Cell Growth and SurvivalTargeted Mutations in the ATR Pathway Define Agent-Specific Requirements for Cancer Cell Growth and Survival
Many anticancer agents induce DNA strand breaks or cause the accumulation of DNA replication intermediates. The protein encoded by ataxia-telangiectasia mutated and Rad 3-related (ATR) generates signals in response to these altered DNA structures and activates cellular survival responses. Accordingly, ATR has drawn increased attention as a potential target for novel therapeutic strategies designed to potentiate the effects of existing drugs. In this study, we use a unique panel of genetically modified human cancer cells to unambiguously test the roles of upstream and downstream components of the ATR pathway in the responses to common therapeutic agents. Upstream, the S-phase-specific cyclin-dependent kinase (Cdk) 2 was required for robust activation of ATR in response to diverse chemotherapeutic agents. While Cdk2-mediated ATR activation promoted cell survival after treatment with many drugs, signaling from ATR directly to the checkpoint kinase Chk1 was required for survival responses to only a ...
NTNU Open: Low expression levels of ATM may substitute for CHEK2/TP53 mutations predicting resistance towards anthracycline and...NTNU Open: Low expression levels of ATM may substitute for CHEK2/TP53 mutations predicting resistance towards anthracycline and...
Introduction Mutations affecting p53 or its upstream activator Chk2 are associated with resistance to DNA-damaging chemotherapy in breast cancer. ATM (Ataxia Telangiectasia Mutated protein) is the key activator of p53 and Chk2 in response to genotoxic stress. Here, we sought to evaluate ATMs potential role in resistance to chemotherapy. Methods We sequenced ATM and assessed gene expression levels in pre-treatment biopsies from 71 locally advanced breast cancers treated in the neoadjuvant setting with doxorubicin monotherapy or mitomycin combined with 5-fluorouracil. Findings were confirmed in a separate patient cohort treated with epirubicin monotherapy. Each tumor was previously analyzed for CHEK2 and TP53 mutation status. Results While ATM mutations were not associated with chemo-resistance, low ATM expression levels predicted chemo-resistance among patients with tumors wild-type for TP53 and CHEK2 (P = 0.028). Analyzing the ATM-chk2-p53 cascade, low ATM levels (defined as the lower 5 to 50% ...
BioDiscovery ATM in focus: A damage sensor and cancer targetBioDiscovery ATM in focus: A damage sensor and cancer target
In terms of the exploiting DDR pathway for therapeutic intervention, the inhibitors of Poly ADP-ribose polymerase-1 have made the greatest progress and many such inhibitors are currently valuated in clinical trials [228]. Following the initial discoveries of inhibitors of ATM [214, 217], the quest for finding compounds with higher specificity and to test them for their therapeutic benefit quickly followed. There are several reports that demonstrate increased cellular sensitivity towards genotoxic agents by way of modulating the ATM signalling pathway through inhibition of ATM kinase specifically. In one of the earliest of such reports, Morgan SE et al (1997) demonstrated that over-expression of a truncated version of the functionally important leucine zipper domain of the ATM gave rise to a dominant negative ATM mutant in colon cancer cells. This group reported that such cells had an increased level of radiosensitivity and chromosomal breakage and an abrogated S-phase checkpoint. Inhibition of ...
ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin. -...ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin. -...
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Admin, Author at TretheraAdmin, Author at Trethera
Abstract Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the […]. ...
Human ATM(Serine-protein kinase ATM) ELISA Kit - Xpress Biotech InternationalHuman ATM(Serine-protein kinase ATM) ELISA Kit - Xpress Biotech International
All of our products are intended to be used for RESEARCH purposes only. They are not intended to be used for drug or diagnostic purposes nor are they intended for human use ...
ATM Phosphorylation of Mdm2 Ser39... preview & related info | MendeleyATM Phosphorylation of Mdm2 Ser39... preview & related info | Mendeley
(2012) Gannon et al. Cancer Cell. DNA damage induced by ionizing radiation activates the ATM kinase, which subsequently stabilizes and activates the p53 tumor suppressor protein. Although phosphorylation of p53 by ATM was found previously to modulate p53 levels and transcriptional activities in v...
Difference between revisions of Talk:CH391L/S2013 Logan R Myler Jan 30 2013 - OpenWetWareDifference between revisions of "Talk:CH391L/S2013 Logan R Myler Jan 30 2013" - OpenWetWare
I think that its tricky to say. The effect of DNAPK inhibitor and ATM inhibitor was the same as that of caffeine in the case of MDC1, suggesting that DNAPK and ATM are both required for a response in that situation. DNA-PKcs is mainly recruited to DSB ends and activated by its regulatory subunit, Ku, which binds to ends (Together they make DNA-PK). (1) ATM on the other hand is recruited to DSBs and activated by MRN, which also binds ends. (2) All of these proteins separately bind MDC1 (DNA-PK, ATM, MRN). The authors used siRNAs against Ku, which did not display any abrogated focus formation, meaning that DNA-PKcs is not being recruited to the focus through Ku. It is not known where on DNA-PK MDC1 binds, but it does bind to the PST repeats on MDC1, which would make me think that it wouldnt inhibit other proteins (ATM, MRN) from binding. If I had to speculate, I would say that there is probably some complicated kinetics between ATM and DNAPK phosphorylation such that DNAPK phosphorylates H2AX ...
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Stokes M (2007) CST Curation Set: 2262; Year: 2007; Biosample/Treatment: cell line, M059K/UV; Disease: glioblastoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 ...
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Stokes M (2007) CST Curation Set: 2262; Year: 2007; Biosample/Treatment: cell line, M059K/UV; Disease: glioblastoma; SILAC: -; Specificities of Antibodies Used to Purify Peptides prior to LCMS: p[ST]Q Antibodies Used to Purify Peptides prior to LCMS: Phospho-(Ser/Thr) ATM/ATR Substrate Antibody Cat#: 2851 ...
QinQ coming in on ATM and out GigaEther... - Cisco Support CommunityQinQ coming in on ATM and out GigaEther... - Cisco Support Community
Hi there Network as shown: Enduser -> eth-to-atm -> C7600 -> switch The enduser uses FastEthernet and have several VLANs. The "eth-to-atm" is a non-cisco based system capable of converting ethernet to atm cells and allowing baby
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Study Reveals Worlds Most Used but Unsafe ATM Pin NumbersStudy Reveals World's Most Used but Unsafe ATM Pin Numbers
Worlds most popular four-digit ATM PIN number combinations, like 1234, are the most dangerous combinations and can be guessed easily, reveals study.
Newborn With Umbilical Cord Still Attached is Found Dead Behind Apartment Building | Inside EditionNewborn With Umbilical Cord Still Attached is Found Dead Behind Apartment Building | Inside Edition
Emergency responders discovered the infant in the rear of 130 W. 183rd St. near Sedgwick Ave. in University Heights, but she could no
Ataxia Telangiectasia (AT) Pipeline Insight, 2020 By DelveInsight - Vizag HeraldAtaxia Telangiectasia (AT) Pipeline Insight, 2020 By DelveInsight - Vizag Herald
Albany, US) DelveInsight has launched a new report on Ataxia Telangiectasia Pipeline. "Ataxia Telangiectasia (AT) Pipeline Insight, 2020" report by DelveInsight outlays comprehensive insights of present clinical development scenario and growth prospects across the Ataxia Telangiectasia (AT) market. A detailed picture of the Ataxia Telangiectasia (AT) pipeline landscape is provided, which includes the disease overview and Ataxia Telangiectasia (AT) treatment guidelines. The assessment part of the report embraces in-depth Ataxia Telangiectasia (AT) commercial assessment and clinical assessment of the Ataxia Telangiectasia (AT) pipeline products from the pre-clinical developmental phase to the marketed phase. In the report, a detailed description of the drug is proffered including mechanism of action of the drug, clinical studies, NDA approvals (if any), and product development activities comprising the technology, Ataxia Telangiectasia (AT) collaborations, licensing, mergers and acquisition, ...
Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress<...Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress<...
TY - JOUR. T1 - Glutathione levels in blood from ataxia telangiectasia patients suggest in vivo adaptive mechanisms to oxidative stress. AU - Degan, Paolo. AU - dIschia, Marco. AU - Pallardó, Federico V.. AU - Zatterale, Adriana. AU - Brusco, Alfredo. AU - Calzone, Rita. AU - Cavalieri, Simona. AU - Kavakli, Kaan. AU - Lloret, Ana. AU - Manini, Paola. AU - Pisanti, Maria Antonietta. AU - Vuttariello, Emilia. AU - Pagano, Giovanni. PY - 2007/6. Y1 - 2007/6. N2 - Objective: To evaluate an in vivo pro-oxidant state in patients with ataxia telangiectasia (AT). Methods: A set of oxidative stress endpoints were measured in 9 AT homozygotes, 16 AT heterozygotes (parents) and 83 controls (grouped in age ranges as for patients and parents, respectively). The following analytes were measured: (a) leukocyte 8-hydroxy-2′-deoxyguanosine (8-OHdG); (b) blood glutathione (GSSG and GSH); and (c) plasma levels of glyoxal (Glx) and methylglyoxal (MGlx). Results: AT patients displayed a significant decrease in ...
DHFR gene amplification in cultured skin fibroblasts of ataxia telangiectasia patients after methotrexate selection<...DHFR gene amplification in cultured skin fibroblasts of ataxia telangiectasia patients after methotrexate selection<...
TY - JOUR. T1 - DHFR gene amplification in cultured skin fibroblasts of ataxia telangiectasia patients after methotrexate selection. AU - Lücke-huhle, Christine. AU - Hinrichs, Susanne. AU - Speit, Günter. PY - 1987/12. Y1 - 1987/12. N2 - During selection for methotrexate resistance, SV40-transformed human skin fibroblasts from patients with ataxia telangiectasia (A-T) underwent amplification of the dihydrofolate reductase (DHFR) gene, experienced nearly complete loss of the integrated SV40 sequences and showed a 3.6-fold increase in Ki-ras gene copy number. Over a period of months methotrexate-resistant (MTXr) A-T subclones were obtained, which were able to grow in progressively increasing MTX concentrations up to 100 μM. The ED50 values determined as the effective dose of MTX causing 50% growth inhibition in comparison to control cells increased from 3×10-2 μM for MTXs AT5BI-VA cells to 250 μM MTX for the MTXr AX100 subclone. In contrast, human skin fibroblasts of healthy individuals did ...
Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts<...Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts<...
TY - JOUR. T1 - Expression of ATM in ataxia telangiectasia fibroblasts rescues defects in DNA double-strand break repair in nuclear extracts. AU - Li, Yuling. AU - Carty, Michael P.. AU - Oakley, Gregory G.. AU - Seidman, Michael M.. AU - Medvedovic, Mario. AU - Dixon, Kathleen. PY - 2001/1/1. Y1 - 2001/1/1. N2 - Ataxia telangiectasia (A-T) is a human genetic disorder characterized by progressive cerebellar degeneration, hypersensitivity to ionizing radiation (IR), immunodeficiency, and high cancer risk. 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. 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 ...
Ataxia Telangiectasia & Immunoglobulin M Decreased: Causes & Reasons - SymptomaAtaxia Telangiectasia & Immunoglobulin M Decreased: Causes & Reasons - Symptoma
Ataxia Telangiectasia & Immunoglobulin M Decreased Symptom Checker: Possible causes include Ataxia Telangiectasia. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
Targeting the Ataxia Telangiectasia Mutated (ATM) kinase for alleviating cancerTargeting the Ataxia Telangiectasia Mutated (ATM) kinase for alleviating cancer
Ravi, Srimadhavi; Barui, Sugata and Kirubakaran, Sivapriya, "Targeting the Ataxia Telangiectasia Mutated (ATM) kinase for alleviating cancer", in the 68th Gordon Research Conference for Natural Products and Bioactive Compounds, Proctor Academy, Andover, NH, US, Jul. 28- Aug. 2, 2019 ...
Activation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53 | ScienceActivation of the ATM Kinase by Ionizing Radiation and Phosphorylation of p53 | Science
Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by clinical manifestations that include progressive cerebellar ataxia, neuronal degeneration, hypersensitivity to ionizing radiation (IR), premature aging, hypogonadism, growth retardation, immune deficiency, and an increased risk for cancer (1). The gene mutated in A-T, ATM (ataxia telangiectasia-mutated), encodes a 370-kD protein that is a member of a family of proteins related to phosphatidylinositol 3-kinase (PI-3-K) that have either lipid or protein kinase activity. The subset of this family with the greatest identity to ATM functions in DNA repair, DNA recombination, and cell-cycle control (2, 3). 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 G1 phase of the cell-cycle mediated by the p53 tumor suppressor gene product (4, 5). In response to DNA damage, cells with wild-type ...
A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 11q22-23. | Journal of Medical...A family showing no evidence of linkage between the ataxia telangiectasia gene and chromosome 11q22-23. | Journal of Medical...
We have studied an inbred family in which two cousins presented with the same clinical features of ataxia telangiectasia (AT). Both patients are still ambulatory at ages 25 and 20. Cellular features of both patients are typical of AT and include increased radiosensitivity and an increased level of spontaneously occurring chromosome aberrations in peripheral blood lymphocytes. Linkage studies and haplotype analysis show no clear evidence that the gene for AT in this family is on chromosome 11q22-23. As previously reported AT families from complementation groups AB, C, and D have all shown linkage to this region of 11q22-23. Our study is of importance in suggesting additional locus heterogeneity.. ...
Ataxia Telangiectasia - National Cancer InstituteAtaxia Telangiectasia - National Cancer Institute
A fact sheet about ataxia telangiectasia (A-T), a rare, recessive genetic disorder of childhood that occurs in between one out of 40,000 and one out of 100,000 persons worldwide.
Introduction The ataxia-telangiectasia mutated (ATM) gene (MIM Identification 208900) encodes a | Inhibition of DNA...Introduction The ataxia-telangiectasia mutated (ATM) gene (MIM Identification 208900) encodes a | Inhibition of DNA...
Introduction The ataxia-telangiectasia mutated (ATM) gene (MIM Identification 208900) encodes a proteins kinase Igf1 Everolimus that has a significant function in the activation of cellular replies to DNA double-strand breaks through subsequent phosphorylation of central players in the DNA damage-response pathway. for breasts cancers remain unresolved. SOLUTIONS TO investigate the function of ATM in BC susceptibility we examined 76 uncommon sequence variations in the ATM gene within a case-control family members research of 2 570 situations of breasts cancers and 1 448 handles. The variations had been grouped into three types predicated on their most likely pathogenicity as dependant on in silico evaluation and examined by conditional logistic regression. Most likely pathogenic sequence variations had been genotyped in 129 family of 27 carrier probands (15 which transported c.7271T > G) and improved segregation analysis was utilized to estimation the BC penetrance connected with these uncommon ...
Ataxia - Telangiectasia: Diseases and Conditions | Pediatric OncallAtaxia - Telangiectasia: Diseases and Conditions | Pediatric Oncall
Ataxia Telangiectasia is a progressive degenerative disease which affects various systems of the body. First signs of the disease usually appear during the second year of life.
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Cellular response to DNA damage is critical to maintain genomic stability. When a double-strand break (DSB) occurs, the cell activates its checkpoint machinery to halt cell cycle progression and allow proper DSB repair (1). Without such response and repair, the cell will eventually undergo apoptosis or pass on its altered DNA to daughter cells. Checkpoints are enabled through sensing DNA damage, transducing damage signals, and activating effectors. Mechanisms by which DNA damage signals are initiated have begun to be revealed (1, 2) . PI-3-like kinases, including ataxia-telangiectasia mutated (ATM), ATM and Rad3-related (ATR), and DNA-PK are believed to play central roles (3). ATM is mutated (lost or inactivated) in the human genetic disorder ataxia-telangiectasia and could be the primary kinase responsible for DSB signaling transduction. Structural chromatin changes activate ATM, which then phosphorylates itself (4). Activated, autophosphorylated ATM in turn phosphorylates the checkpoint ...
Ataxia-telangiectasia synonyms, Ataxia-telangiectasia antonyms - FreeThesaurus.comAtaxia-telangiectasia synonyms, Ataxia-telangiectasia antonyms - FreeThesaurus.com
Synonyms for Ataxia-telangiectasia in Free Thesaurus. Antonyms for Ataxia-telangiectasia. 3 synonyms for ataxia: ataxy, dyssynergia, motor ataxia. What are synonyms for Ataxia-telangiectasia?
Complex Response to DNA Damage | Science SignalingComplex Response to DNA Damage | Science Signaling
Cells avoid the disastrous effects of DNA damage by activating a checkpoint mechanism to prevent proliferation of cells that contain damaged DNA. The protein kinase ATM is an important component of this signaling mechanism, but precisely how its activity is regulated has not been clear. The protein Nbs1, which is mutated in the human disorder Nijmegen breakage syndrome, forms MRN complexes with two other proteins that participate in DNA repair, Mre11 and Rad50 (Mre11-Rad50-Nbs1, hence, MRN). Nbs is also a substrate for ATM. But now, Lee and Paull suggest that the interaction between Nbs1 and ATM is more complicated. MRN complexes directly activate enzymatic activity of ATM, possibly by causing a conformational change in ATM that alters the affinity of the kinase toward its substrates.. J.-H. Lee, T. T. Paull, Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex. Science 304, 93-96 (2004). [Abstract] [Full Text]. ...
miRNA Regulation of DNA Damage Response (Homo sapiens) - WikiPathwaysmiRNA Regulation of DNA Damage Response (Homo sapiens) - WikiPathways
This is the first out of two pathways which deals with the DNA damage response. It is comprised of two central gene products (ATM and ATR) influenced by different sources of DNA damage (in blue). The two central genes can both be divides into their most important genes. For the ATM pathway these are TP53 and CHEK2, while CHEK1 is most important for the ATR pathway. The goal of this first pathway is to provide an overview of the most important gene products, processes and changes in cell condition elicited by the DNA damage response while keeping it clear and understandable. Also some microRNAs are implemented to visualize the possible effects they can induce. By doing so a better understanding of the role microRNA play in the DNA damage response might arise. All processes take place in the cytoplasm, except when mentioned differently. ...
Scientists Visualize Structure of Key DNA Repair Component with Near-Atomic Resolution---Chinese Academy of SciencesScientists Visualize Structure of Key DNA Repair Component with 'Near-Atomic Resolution'---Chinese Academy of Sciences
Artists concept of Launching the cellular DNA-damage response by the ATR-ATRIP complex. (Image by WANG Guoyan and CHEN Lei, USTC). The researchers published the structural information on Dec 1st in Science.. "The ATR protein is the apical kinase to cope with the DNA damages and replication stress," said CAI Gang, a professor of life sciences at the University of Science & Technology of China in Hefei, China, and the lead author on the paper. "It has long been a central question to determine the activation mechanism of ATR kinase-how it responds to DNA damage and how it is activated.". CAI and his team used electron microscopy to image the Mec1-Ddc2 complex at 3.9 ångströms, which is about eight times the size of a single atom of helium. The complex is found in yeast and is the equivalent of the human ATR protein and its cell-signaling protein partner, ATRIP.. The ATR kinase is one of six proteins responsible for maintaining the health of the cell. When this family of proteins identifies a ...
miRNA Regulation of DNA Damage Response (Homo sapiens) - WikiPathwaysmiRNA Regulation of DNA Damage Response (Homo sapiens) - WikiPathways
This is the first pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and ATR) which are connected to the sources of DNA damage (in blue). The two central genes can be divides furthermore into their most important genes. In the ATM pathway are the most important genes TP53 and CHEK2 and on the other hand in the ATR pathway is this CHEK1. If it is not mentioned different, the processes take place in the cell cytoplasm. The goal of this first pathway is to give an overview of the most important gene products, processes and changes in the cell condition through the DNA damage response pathway and at the same time to keep it clearly ...
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Because of potential chemotherapeutic (sensitization of chemoresistant cells to death; refs. 3, 4) and chemopreventive (skin cancer prevention; ref. 35) implications, ATR pathway inhibitors have long been sought. Caffeine has been widely used as an ATM/ATR inhibitor, but caffeine requires millimolar levels to inhibit ATR and has several other targets (12, 36). Previous attempts to discover novel DNA damage response inhibitors have focused on finding better ATP-competitive inhibitors of kinases in this pathway. In the present study, we used a phenotype-based screening approach to identify ATR pathway inhibitors, potentially mechanistically distinct from typical ATP-competitive kinase inhibitors. Because the ATR activation mechanism is complex and requires multiple proteins to be recruited to damaged DNA, any of these components of the ATR pathway could potentially be a target of the identified small-molecule inhibitors. Specifically, unlike traditional biochemical screening, this phenotype-based ...
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In this issue of Clinical Cancer Research, Saiya-Cork and colleagues used integrative genomic profiling to identify that the insulin receptor (INSR) is significantly overexpressed in about 25% of chronic lymphocytic leukemias (CLL), many of which carry deletion 11q (1). Deletion 11q has been associated with marked lymphadenopathy and rapid disease progression in CLL, leading to short overall survival (2, 3). At diagnosis or initiation of first therapy, deletion 11q is the most common high-risk abnormality in CLL. Although the molecular pathogenesis of CLL with each characteristic chromosome abnormality is being intensively studied, much remains to be understood. Most interest in 11q deletion has focused on loss of the ataxia telangiectasia mutated (ATM) gene, a well-known tumor suppressor gene involved in cell cycle checkpoint signaling and DNA repair. Because 11q deletion generally only affects one of the two chromosomes, the other ATM allele would be expected to be mutated if ATM is a key ...
Frontiers | DNA Damage Response and Immune Defense: Links and Mechanisms | GeneticsFrontiers | DNA Damage Response and Immune Defense: Links and Mechanisms | Genetics
DNA damage plays a causal role in numerous human pathologies including cancer, premature aging and chronic inflammatory conditions. In response to genotoxic insults, the DNA damage response (DDR) orchestrates DNA damage checkpoint activation and facilitates the removal of DNA lesions. The DDR can also arouse the immune system by for example inducing the expression of antimicrobial peptides as well as ligands for receptors found on immune cells. The activation of immune signalling is triggered by different components of the DDR including DNA damage sensors, transducer kinases, and effectors. In this review, we describe recent advances on the understanding of the role of DDR in activating immune signalling. We highlight evidence gained into (i) which molecular and cellular pathways of DDR activate immune signalling, (ii) how DNA damage drives chronic inflammation, and (iii) how chronic inflammation causes DNA damage and pathology in humans.
ataxia telangiectasia | HealthInfiataxia telangiectasia | HealthInfi
Healthinfi.Com Provides Valuable Health Information, Tools for managing your health, and support to those who seek information. You can trust that our content is timely and credible ...
9th Annual Pasta Bar for a Cure of Ataxia Telangiectasia | Visit Sarasota9th Annual Pasta Bar for a Cure of Ataxia Telangiectasia | Visit Sarasota
Food, wine & gelato bars, live music & dancing, lively auction, raffle and more! Enjoy a night under the stars at Wobbly Feet Foundations signature event... October 20th in Englewood, FL!
Disease InfoSearch - Ataxia Telangiectasia - Definition, causes, resources and support informationDisease InfoSearch - Ataxia Telangiectasia - Definition, causes, resources and support information
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Selective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia | SpringerLinkSelective deficiency of CD4+/CD45RA+ lymphocytes in patients with ataxia-telangiectasia | SpringerLink
Several immunological abnormalities have been observed in ataxia-telangiectasia (AT), the most consistent being defects of immunoglobulin isotypes, decreased T-cell numbers, and reduced proliferative...
ATM Kinase Inhibitor, KU-55933 | ABIN412287ATM Kinase Inhibitor, KU-55933 | ABIN412287
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Comment on ATRComment on ATR
14-3-3 tau mediates E2F1 stabilization. 14-3-3 tau interacts with ATM-phosphorylated E2F1 during DNA damage and inhibits E2F1 ubiquitination. 14-3-3 tau is also required for expression and induction of E2F1 apoptotic targets, such as p73, Apaf-1, and caspases, during DNA damage ...
Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors. | Sigma-AldrichKinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors. | Sigma-Aldrich
Sigma-Aldrich offers abstracts and full-text articles by [Kenta Yamamoto, Jiguang Wang, Lisa Sprinzen, Jun Xu, Christopher J Haddock, Chen Li, Brian J Lee, Denis G Loredan, Wenxia Jiang, Alessandro Vindigni, Dong Wang, Raul Rabadan, Shan Zha].
ATM (Human) Recombinant Protein (P01) - (H00000472-P01) - Products - AbnovaATM (Human) Recombinant Protein (P01) - (H00000472-P01) - Products - Abnova
Human ATM full-length ORF (AAH07023.1, 1 a.a. - 138 a.a.) recombinant protein with GST-tag at N-terminal. (H00000472-P01) - Products - Abnova
Newly discovered cellular process helps cells respond to DNA damageNewly discovered cellular process helps cells respond to DNA damage
Such an assay has many obvious potential uses," Kastan said, "including the assessment of exposure to dangerous agents in the environment." Another potential clinical benefit of these discoveries applies to cancer prevention. Since damage to the DNA appears to contribute to the vast majority of human cancers, enhancing the response of cells to DNA damage could reduce cancer development, Kastan noted. Therefore, the discovery of how ATM is activated could help guide the development of ways to improve cellular responses to DNA damage, including responses to oxidative stress that are either induced or natural ...
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Recent efforts to understand the biochemical basis for ATR activation at stalled DNA replication forks have led to new insight into how ATR is regulated and how ATR in turn regulates a network of downstream signaling molecules (9). The seminal observation by Reinhardt and colleagues that loss of p53 function, which occurs in approximately 50% of all cancers, functionally "rewires" the pathways downstream of ATR underscores the complexity of these survival pathways (7). A detailed understanding of how these pathways are activated by specific therapeutic agents is needed to formulate combinatorial strategies that can successfully create and exploit survival defects. Our study shows, from a genetic standpoint, that not all prospective molecular targets are equivalent, even though they may function in a common pathway. Genetic inhibition of ATR and Cdk2 showed distinct effects from the genetic or pharmacologic inhibition of Chk1 (Figs. 1B, 5B, and 6A).. The HCT116 and DLD-1 cell lines harbor ...
OriGene - ATM (NM 007499) shRNAOriGene - ATM (NM 007499) shRNA
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Vodafone and Link sign ATM phone top-up dealVodafone and Link sign ATM phone top-up deal
We envisage the time when customers of any mobile operator will be able to top up their airtime at any UK ATM, said Nigel Wright, operations and development director at Link. This deal paves the way for members of the Link network to offer the services at their ATMs ...
Your PC ATM | Page 415 | TechPowerUp ForumsYour PC ATM | Page 415 | TechPowerUp Forums
I just used Prime95 cause it generates the most heat. linX doesnt do a good job. i believe InteBurnTest is the best Are you using custom settings? For me...
The most insightful stories about Ataxia Telangiectasia - MediumThe most insightful stories about Ataxia Telangiectasia - Medium
Read stories about Ataxia Telangiectasia on Medium. Discover smart, unique perspectives on Ataxia Telangiectasia and the topics that matter most to you like care coordination, cscw2019, eltern, healthcare, and hoffnung.
A study of the role of ATM mutations in the pathogenesis of B-cell chronic lymphocytic leukaemia - eTheses RepositoryA study of the role of ATM mutations in the pathogenesis of B-cell chronic lymphocytic leukaemia - eTheses Repository
Mutations in the ATM gene have previously been identified in CLL tumours. In this project, I have demonstrated that their detection would have prognostic value. With a prevalence of 12%, ATM mutations represent the commonest single gene defect to be detected in CLL tumours and they identified a subgroup of CLL patients that had a significant reduction in both treatment free and overall survival. Furthermore, ATM mutations provided prognostic information that was independent of age, clinical stage, the mutation status of the IGVH genes and TP53 mutations. The temporal acquisition of the ATM mutations and their relationship with loss of an ATM allele via a chromosomal 11q deletion provides clues into their mechanism of action. There was only a partial correlation between CLL tumours with mutations in the ATM gene and those with a chromosome 11q deletion. In certain cases, the ATM mutations represented germ-line changes and in others were acquired very early in the disease course raising the ...
H2AX phosphorylation after UV irradiation is triggered by DNA repair intermediates and is mediated by the ATR kinase :...H2AX phosphorylation after UV irradiation is triggered by DNA repair intermediates and is mediated by the ATR kinase :...
It has been suggested that phosphorylation of the histone variant H2AX after ultraviolet light (UV) irradiation is triggered by DNA double-strand breaks induced as replication forks collide with UV-induced bulky lesions. More recently, it has been shown that UV-induced H2AX phosphorylation can also occur outside of S-phase, but the mechanism for this replication-independent induction is not well understood. In this study, we show that H2AX phosphorylation after UV irradiation is triggered by DNA repair intermediates and is induced in all phases of the cell cycle. Accumulation of DNA repair intermediates by inhibition of DNA repair synthesis resulted in a marked increase of H2AX phosphorylation in repair proficient but not repair-deficient xeroderma pigmentosum-A cells. Using chemical inhibitors of the PI(3)-like kinase family of protein kinases as well as ataxia telangiectasia mutated and Rad-3 related (ATR)-deficient Seckel syndrome cells and ataxia telangiectasia mutated-deficient ataxia ...
Image-based quantitative determination of DNA damage signal reveals a threshold for G2 checkpoint activation in response to...Image-based quantitative determination of DNA damage signal reveals a threshold for G2 checkpoint activation in response to...
Proteins involved in the DNA damage response accumulate as microscopically-visible nuclear foci on the chromatin flanking DNA double-strand breaks (DSBs). As growth of ionizing radiation (IR)-induced foci amplifies the ATM-dependent DNA damage signal, the formation of discrete foci plays a crucial role in cell cycle checkpoint activation, especially in cells exposed to lower doses of IR. However, there is no quantitative parameter for the foci which considers both the number and their size. Therefore, we have developed a novel parameter for DNA damage signal based on the image analysis of the foci and quantified the amount of the signal sufficient for G2 arrest. The parameter that we have developed here was designated as SOID. SOID is an abbreviation of Sum Of Integrated Density, which represents the sum of fluorescence of each focus within one nucleus. The SOID was calculated for individual nucleus as the sum of (area (total pixel numbers) of each focus) x (mean fluorescence intensity per pixel of each
The Validity of Forced Expiratory Maneuvers in Ataxia Telangiectasia Studied Longitudinally - Full Text View - ClinicalTrials...The Validity of Forced Expiratory Maneuvers in Ataxia Telangiectasia Studied Longitudinally - Full Text View - ClinicalTrials...
Rationale: Forced spirometry maneuvers are not routinely performed in patients with Ataxia Telangiectasia (A-T), even though they suffer from respiratory illnesses.. Objectives: To study the feasibility and validity of forced spirometry in A-T patients.. Methods: Patients will perform spirometry during clinical visits. Parameters studied will be technical quality, relation to predicted values, age, pulmonary illness, body mass index, mutational status and mutation. ...
Ataxia telangiectasia syndrome definition | Drugs.comAtaxia telangiectasia syndrome definition | Drugs.com
Definition of ataxia telangiectasia syndrome. Provided by Stedmans medical dictionary and Drugs.com. Includes medical terms and definitions.
ATM directs DNA damage responses and proteostasis via genetically separable pathways | Science SignalingATM directs DNA damage responses and proteostasis via genetically separable pathways | Science Signaling
The kinase ATM is classically known for its role in coordinating the response to DNA damage. DNA damage is caused by various intracellular and extracellular stimuli, including oxidative stress and free radicals. Lee et al. found critical amino acid residues that enable ATM to coordinate a response to DNA damage that is independent of its response to oxidative stress. Activation of ATM by either pathway promoted mitochondrial function and autophagy, thus mediating cell survival through metabolic changes. ATM activation via oxidative stress additionally promoted the clearance of toxic protein aggregates. These findings expand the roles of ATM and suggest that the loss of ATM function, such as in the neurodegenerative disease ataxia telangiectasia (A-T), causes broader cellular stress than that limited to a defective DNA damage response. ...
Novel Roles of Replication Protein A Phosphorylation in Cellular Respo by Moises A. Serrano"Novel Roles of Replication Protein A Phosphorylation in Cellular Respo" by Moises A. Serrano
Human replication protein A (RPA) is an eukaryotic single-stranded DNA binding protein directly involved in a variety of DNA metabolic pathways including replication, recombination, DNA damage checkpoints and signaling, as well as all DNA repair pathways. This project presents 2 novel roles of RPA in the cellular response to DNA damage. The first elucidates the regulation of RPA and p53 interaction by DNA-dependent protein kinase (DNA-PK), ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) in homologous recombination (HR). HR and nonhomologous end joining (NHEJ) are 2 distinct DNA double-stranded break (DSB) repair pathways. Here, we report that DNA-PK, the core component of NHEJ, partners with DNA-damage checkpoint kinases ATM, and ATR to synergistically regulate HR repair of DSBs. The regulation was accomplished through modulation of the p53-RPA interaction. We show that upon DNA damage p53 and RPA are freed from the p53-RPA complex. This is done through simultaneous phosphorylation
LIM Protein Ajuba Participates in the Repression of ATR-Mediated DNA D by Sampada Kalan"LIM Protein Ajuba Participates in the Repression of ATR-Mediated DNA D" by Sampada Kalan
LIM proteins constitute a superfamily characterized by the presence of specialized domains called LIM. LIM domain is a unique double-zinc finger motif found in a variety of proteins and is mainly involved in protein-protein interactions. Previous work has implicated that members of the Zyxin subfamily of LIM proteins, namely TRIP6 and LPP are involved in the repression of the DNA damage response (DDR) at telomeres. We further explore if another member from this family has an influence on DDR prevention in the cells. Here, we describe a novel role for Ajuba, a Zyxin family LIM protein, in repressing inappropriate activation of ATR kinase mediated DDR. We found that depletion of Ajuba led to a decrease in cell proliferation, apparent delay in the cell cycle, accompanied with increased phosphorylation of Retinoblastoma protein (Rb). We detect that reduction of Ajuba leads to Chk1 phosphorylation, indicative of ATR activation in cells. We also observe induction of p53 and cell death by apoptosis in the
Circadian rhythm and its role in malignancy | Journal of Circadian Rhythms | Full TextCircadian rhythm and its role in malignancy | Journal of Circadian Rhythms | Full Text
The circadian control of an organisms response to DNA damage response rests upon circadian proteins which play important roles in the processes of cell proliferation and control of response to genotoxic stress both at the cellular and organismal levels [83]. DNA damage triggers cellular stress response pathways which may result in checkpoint cell cycle arrest, apoptosis or DNA repair. DNA damage leads to activation of critical components of cellular stress response pathways including ATM/ATR (ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related) and CHK1/2 (checkpoint kinase1/2) which in turn activates tumour suppressor protein p53 and subsequently causes cell cycle arrest or apoptosis [84]. It has been shown that Bmal1-deficient human cells are unable to undergo growth arrest on p53 activation by DNA damage. Contrary to in vivo mouse data connecting BMAL1-dependent delay in G1 progression to upregulation of p21 [82], radiation induced growth arrest in Bmal1-deficient human ...
Serine/threonine-protein kinase ATRSerine/threonine-protein kinase ATR
The protein encoded by this gene belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. 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. This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. Mutations of this gene are associated with Seckel syndrome. An alternatively spliced transcript variant of this gene has been reported, however, its full length nature is not known. Transcript variants utilizing alternative polyA sites exist. [provided by RefSeq, Jul 2008 ...
Associazione Nazionale A-T via Rinalducci, 30 Fano (PU)Associazione Nazionale A-T via Rinalducci, 30 Fano (PU)
Different excellence centers in Italy and in the world are involved in research projects aimed to define the role of ATM protein in the AT physiopathology the ATM protein. To know the mechanisms that lead to neurodegeneration as a result of the lack of ATM and basilar protein to understand the symptoms of the patients with AT and to propose new therapeutic strategies. ANAT finances for years the following research projects:. In the last years it was proposed that ATM protein is involved in defense mechanisms to oxidative stress and in metabolism.. Projects title: The role of ATM in the control of cellular metabolism Scientific responsible: Doc. Vincenzo Costanzo. Host institute: IFOM, FIRC Institute of Molecular Oncology (Milan). The molecular basis of corticosteroids efficiency in the improvement of neurological symptoms at patients with AT are still research objects.. Project title: Corticosteroids for patients with Ataxia Telangiectasia (AT): the dexamethasone effect on AT cells activity ...
ATR Takes ATRIP to Fix Defects: Protein partners watch over the genome (DNA damage) -- Davenport 2001 (9): 35 -- <i>Science</i...ATR Takes ATRIP to Fix Defects: Protein partners watch over the genome (DNA damage) -- Davenport 2001 (9): 35 -- <i>Science</i...
R. John Davenport http://sageke.sciencemag.org/cgi/content/abstract/sageke;2001/9/nw35 Key Words: genomic instability ATR ATM Ataxia telangiectasia DNA repair double-strand breaks RAD26 DDC2. Abstract: In eukaryotic cells, protein sentries ensure that the genome is complete before cell division proceeds. When DNA is damaged or its replication machinery conks out, the genome guardians attach phosphate groups to other proteins; this chemical addition triggers these proteins to bring the cell cycle to a halt and activate DNA repair machinery. A breakdown in this system can impair health: People with a defective copy of the gene for one of those proteins--called ATM--suffer from a disorder known as ataxia telangiectasia (see Transgenic Mouse Entries: tg1, tg2, and tg3). Symptoms of the disorder include neuronal degeneration, weakened immunity, and increased risk of cancer. Although scientists know a fair amount about ATM, key information is missing about the activities of a related ...
RPA-coated single-stranded DNA promotes the ETAA1-dependent activation of ATR - CaltechAUTHORSRPA-coated single-stranded DNA promotes the ETAA1-dependent activation of ATR - CaltechAUTHORS
Besides TopBP1, ETAA1 has been identified more recently as an activator of the ATR-ATRIP complex in human cells. We have examined the role of ETAA1 in the Xenopus egg-extract system, which has been instrumental in the study of ATR-ATRIP. Depletion of ETAA1 from egg extracts did not noticeably reduce the activation of ATR-ATRIP in response to replication stress, as monitored by the ATR-dependent phosphorylation of Chk1 and RPA. Moreover, lack of ETAA1 did not appear to affect DNA replication during an unperturbed S-phase. Significantly, we find that TopBP1 is considerably more abundant than ETAA1 in egg extracts. We proceeded to show that ETAA1 could support the activation of ATR-ATRIP in response to replication stress if we increased its concentration in egg extracts by adding extra full-length recombinant ETAA1. Thus, TopBP1 appears to be the predominant activator of ATR-ATRIP in response to replication stress in this system. We have also explored the biochemical mechanism by which ETAA1 ...
Molecular mechanisms of lung disease in ataxia telangiectasia - Joann SekiguchiMolecular mechanisms of lung disease in ataxia telangiectasia - Joann Sekiguchi
Ataxia-telangiectasia (A-T) is a rare, autosomal recessive human disorder characterized by cerebellar ataxia, immunodeficiency, cancer predisposition, recurrent...
Ataxia-telangiectasia - WikipediaAtaxia-telangiectasia - Wikipedia
Ataxia-telangiectasia (AT or A-T), also referred to as ataxia-telangiectasia syndrome or Louis-Bar syndrome, is a rare, neurodegenerative, autosomal recessive disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dilated blood vessels, both of which are hallmarks of the disease. A-T affects many parts of the body: It impairs certain areas of the brain including the cerebellum, causing difficulty with movement and coordination. It weakens the immune system, causing a predisposition to infection. It prevents repair of broken DNA, increasing the risk of cancer. Symptoms most often first appear in early childhood (the toddler stage) when children begin to walk. Though they usually start walking at a normal age, they wobble or sway when walking, standing still or sitting, and may appear almost as if they are drunk. In late pre-school and early school age, they develop difficulty moving their eyes in a natural manner from one place to the next (oculomotor ...
Plasma induced DNA damage: Comparison with the effects of ionizing radiation (Journal Article) | SciTech ConnectPlasma induced DNA damage: Comparison with the effects of ionizing radiation (Journal Article) | SciTech Connect
We use human primary fibroblasts for comparing plasma and gamma rays induced DNA damage. In both cases, DNA strand breaks occur, but of fundamentally different nature. Unlike gamma exposure, contact with plasma predominantly leads to single strand breaks and base-damages, while double strand breaks are mainly consequence of the cell repair mechanisms. Different cell signaling mechanisms are detected confirming this (ataxia telangiectasia mutated - ATM and ataxia telangiectasia and Rad3 related - ATR, respectively). The effective plasma doses can be tuned to match the typical therapeutic doses of 2 Gy. Tailoring the effective dose through plasma power and duration of the treatment enables safety precautions mainly by inducing apoptosis and consequently reduced frequency of micronuclei. ...
Loss of the ataxia-telangiectasia gene product causes oxidative damage in target organs | PNASLoss of the ataxia-telangiectasia gene product causes oxidative damage in target organs | PNAS
Our experimental results establish that tissues from Atm-deficient mice are under oxidative stress and suffer oxidative damage. We and others have identified defects in molecular pathways that lead to abnormalities in the response of cells to ionizing radiation, meiosis, and T cell development where DNA double-strand breaks occur (1, 3-5, 20-23). In addition, several reports have implicated ATM as a serine protein kinase that phosphorylates p53 and chk2, leading to cell cycle arrest after ionizing radiation (24-27). Why would defects in these pathways result in oxidative stress, especially in the adult brain? The majority of cells in the central nervous system are postmitotic and there is no evidence of DNA recombination or significant DNA double-strand breaks in the central nervous system in the absence of ionizing radiation. We infer that ATM also functions to protect biomolecules other than DNA from oxidative damage. Studies from many investigators have established that lipids and proteins ...
The effect of ataxia-telangiectasia mutated kinase-dependent hyperphos | OTTThe effect of ataxia-telangiectasia mutated kinase-dependent hyperphos | OTT
The effect of ataxia-telangiectasia mutated kinase-dependent hyperphosphorylation of checkpoint kinase-2 on oligodeoxynucleotide 7909 containing CpG motifs-enhanced sensitivity to X-rays in human lung adenocarcinoma A549 cells Xiaoqun Liu,1,* Xiangdong Liu,2,* Tiankui Qiao,1 Wei Chen,1 Sujuan Yuan1 1Department of Oncology, 2Department of Ophthalmology, Affiliated Jinshan Hospital, Fudan University, Shanghai, People’s Republic of China *These authors contributed equally to this work Objective: The aim of the study reported here was to further investigate the potential effect of ataxia-telangiectasia mutated (ATM) kinase-dependent hyperphosphorylation of checkpoint kinase-2 (Chk2) on radiosensitivity enhanced by oligodeoxynucleotide 7909 containing CpG motifs (CpG ODN7909) in human lung adenocarcinoma A549 cells. Methods: In vitro A549 cells were randomly separated into control, CpG, X-ray, CpG+X-ray, ATM kinase-small interfering RNA (siRNA)+CpG+X-ray (ATM-siRNA), and Chk2-siRNA+CpG+X-ray
TRANSLATIONAL IMPACT | Disease Models & MechanismsTRANSLATIONAL IMPACT | Disease Models & Mechanisms
Ataxia telangiectasia (A-T) is a rare, recessive, neurodegenerative disease, with symptoms that normally appear in early childhood. Initial indications are usually ataxia (a lack of muscle control leading to loss of balance and coordination) and telangiectasia (tiny red veins, which are most noticeable on the whites of the eyes). The most serious clinical problem is loss of Purkinje cells, leading to degeneration of the cerebellum (the bodys motor control centre). About 70% of sufferers also have thymic hypoplasia and a compromised immune system. Patients are also highly sensitive to X-irradiation and are susceptible to malignant tumors. Currently, there is no cure, nor any treatment that halts the progression of the disease.. A-T is caused by mutation of the ATM gene, which encodes a ubiquitous 370-kD serine-threonine kinase that is essential for normal repair of double-stranded DNA breaks; loss of ATM function results in DNA instability. However, there are atypical cases of A-T in which ATM ...
ataxia telangiectasia - oiataxia telangiectasia - oi
An inherited (autosomal recessive) neurological disorder. Ataxia is usually noted early in life, and a key feature is the presence of dilated blood vessels visible in the sclerae of the eyes and on the cheeks and ears. Other symptoms may include slow slurred speech, abnormal eye movements, skin lesions, and immune deficiency. Affected individuals may develop malignant disease. A raised level of alpha-fetoprotein is found in the blood. ...
Ataxia Telangiectasia (Louis-Bar syndrome)Ataxia Telangiectasia (Louis-Bar syndrome)
Pain management information for pain medicine healthcare professionals in treating and caring for their patients. Clinical Pain Advisor offers news, case studies and more.
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The am of Haykar the Sage. The lab of Al-Bundukani or, The Caliph Harun Al-Rashid and the Daughter of King Kisra. The Tale of the Warlock and the Young Cook of Baghdad.
This Week in Science | ScienceThis Week in Science | Science
In a critical process known as the "DNA damage checkpoint," cells monitor their DNA for damage and halt cell division until the damage has been repaired. Kondo et al. (p. 867) now show that two yeast proteins that function in signaling that DNA damage has occurred actually bind close to the site of damage, but do so in distinct ways. They used a chromatin immunoprecipitation method to detect proteins that bound to double-stranded break in the DNA resulting from continuous expression of the HO endonuclease. One of the proteins bound, Mec1, belongs to a family of protein kinases that includes the ATM protein mutated in the human disease ataxia telangiectasia. Another protein bound at the site of damage was Ddc1, itself thought to be a DNA-binding protein that may recruit other proteins to a complex formed at the damage site. Recruitment of Ddc1, but not that of Mec1, required the action of another participant in the checkpoint pathway, called Rad24. The results help clarify how cells recognize ...
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Both ATM and ATR display a preference for phosphorylating SQ/TQ motifs in their substrates (Kim et al., 1999; Traven and Heierhorst, 2005; Shiloh, 2006). ATR is predominantly activated by UV light and stalled replication forks, whereas ATM is specifically activated by DSBs of DNA, as seen after irradiation, etoposide, or oxidative stress (Abraham, 2001; Shiloh, 2006). In contrast, treatment with the ATP-competitive kinase inhibitor, staurosporine, does not activate ATM or affect the phosphorylation status of ATM-dependent substrates (Kamer et al., 2005). We show here that DNA-damaging agents, such as IR and etoposide, trigger MEF2D phosphorylation. Moreover, MEF2D phosphorylation only increased after etoposide exposure in wt-ATM cells but not in ATM-deficient cells. These results suggest that ATM mediates MEF2D phosphorylation in response to DSBs in DNA.. Furthermore, in the present study, RNA interference-mediated knockdown experiments in cerebellar granule cells indicate that endogenous MEF2D ...
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Exposure to hypoxia-induced replication arrest initiates a DNA damage response which includes both ATR and ATM-mediated signalling. DNA fiber analysis was used to show that these conditions lead to a replication arrest during both the initiation and elongation phases and that this correlated with decreased levels of nucleotides. The DNA damage response induced by hypoxia is distinct from the classical pathways induced by damaging agents primarily due to the lack of detectable DNA damage but also due to the coincident repression of DNA repair in hypoxic conditions. The principle aims of the hypoxia-induced DNA damage response appear to be the induction of p53-dependent apoptosis or the preservation of replication fork integrity. The latter is of particular importance should reoxygenation occur. Tumor reoxygenation occurs as a result of spontaneous changes in blood flow and also therapy. Cells experiencing hypoxia/reoxygenation are therefore sensitive to loss or inhibition of components of the DNA ...
Individual Cytokines Modulate the Neurological Symptoms of ATM Deficiency in a Region Specific Manner | eNeuroIndividual Cytokines Modulate the Neurological Symptoms of ATM Deficiency in a Region Specific Manner | eNeuro
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Possibly Dystonia Only Causes & Reasons - SymptomaPossibly Dystonia Only Causes & Reasons - Symptoma
Possibly Dystonia Only Symptom Checker: Possible causes include Ataxia Telangiectasia. Check the full list of possible causes and conditions now! Talk to our Chatbot to narrow down your search.
Identification of ATR-Chk1 pathway inhibitors that selectively target p53-deficient cells without directly suppressing ATR...Identification of ATR-Chk1 pathway inhibitors that selectively target p53-deficient cells without directly suppressing ATR...
Resistance to DNA-damaging chemotherapy is a barrier to effective treatment that appears to be augmented by p53 functional deficiency in many cancers. In p53-deficient cells in which the G1-S checkpoint is compromised, cell viability after DNA damage relies upon intact intra-S and G2-M checkpoints m …
ATM Inhibitor Products|Active Biopharma CorpATM Inhibitor Products|Active Biopharma Corp
Inhibitors,Activator,Agonist,antagonist,API,Aurora,Metabolic Disease,VEGFR-PDGFR,Other Intermediate,Others,MOF Chemicals,,Active Biopharma Corp
Defective ATM Gene Increases the Risk of Breast CancerDefective ATM Gene Increases the Risk of Breast Cancer
Researchers at the Institute Of Cancer Research have discovered a new breast cancer gene which increases the risk of developing the disease.
ATM Benchmarking Study - AccentureATM Benchmarking Study - Accenture
Read Accentures 2016 global ATM Benchmarking Study, which reinforces the central position the ATM occupies in todays omni-channel banking environment.
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When a human cell detects damaged DNA, it initiates the DNA damage response (DDR) that permits it to repair the damage and avoid transmitting it to daughter cells. Despite this response, changes to the genome occur and ...
Search Articles | University of Toronto LibrariesSearch Articles | University of Toronto Libraries
Targeted therapy based on inhibiting the DNA damage response (DDR) in cancers offers the potential for a greater therapeutic window by tailoring treatment to patients with tumors lacking specific DDR functions ...
Keeping 53BP1 out of focus in mitosis.Keeping 53BP1 out of focus in mitosis.
A recent study published in Science reveals the mechanism and biological importance of DNA damage response abrogation in mitotic cells....
OriGene - ATR (NM 001184) shRNAOriGene - ATR (NM 001184) shRNA
ATR - ATR - Human, 4 unique 29mer shRNA constructs in retroviral untagged vector shRNA available for purchase from OriGene - Your Gene Company.
Festina Swarowski - Hvitfeldt Smykker & UreFestina Swarowski - Hvitfeldt Smykker & Ure
Kassen er vandtæt til 5 atm, og glasset er af mineralglas.. Uret er vandtæt til 5 atm. Dvs. uret er tæt til almindeligt brug og tåler vandstænk. Uret må dog ikke bruges til badning.. ...
Do protein bars expire? | HondaSwapDo protein bars expire? | HondaSwap
Ive had one in my mini fridge for like 6 or so months now and Im eating it atm. Its been pretty much frozen, so Ive assumed its been well...
AutophosphorylationAutophosphorylation
RAD17RAD17
SMC1ASMC1A
BRAT1BRAT1
ATM serine/threonine kinaseATM serine/threonine kinase
Phosphoinositide 3-kinasePhosphoinositide 3-kinase
RAD51RAD51
BRCA1BRCA1
Cancer epigeneticsCancer epigenetics
DNA repairDNA repair
Chromosome 11 (human)Chromosome 11 (human)
RHEBRHEB
LENG9LENG9
TERF1TERF1
RRM2BRRM2B
Artemis (protein)Artemis (protein)
MRE11AMRE11A
Bloom syndrome proteinBloom syndrome protein
NibrinNibrin
TRIM28TRIM28
Ataxia telangiectasia and Rad3 relatedAtaxia telangiectasia and Rad3 related
CHEK2CHEK2
Establishment of sister chromatid cohesionEstablishment of sister chromatid cohesion
Reactive oxygen speciesReactive oxygen species
BRCA1 - Wikipédia, a enciclopédia livreBRCA1 - Wikipédia, a enciclopédia livre
Penelope JeggoPenelope Jeggo
FANCD2FANCD2
PLK3PLK3
BRCA1BRCA1
H2AFXH2AFX
Amyotrophic lateral sclerosisAmyotrophic lateral sclerosis
Cyclin-dependent kinase 4Cyclin-dependent kinase 4
Leigh syndromeLeigh syndrome
Progeroid syndromesProgeroid syndromes
Citron kinaseCitron kinase
Cancer syndromeCancer syndrome
BCKDHABCKDHA
Pancreatic cancerPancreatic cancer
PRKCQPRKCQ
MAST1MAST1
MAP2K6MAP2K6
Li-Fraumeni syndromeLi-Fraumeni syndrome
DNA repair-deficiency disorderDNA repair-deficiency disorder
MAP2K1MAP2K1
STK19STK19
LKB1, wolna encyklopediaLKB1, wolna encyklopedia
Genetic disorderGenetic disorder
Mitogen-activated protein kinaseMitogen-activated protein kinase
Ostra białaczka szpikowa, wolna encyklopediaOstra białaczka szpikowa, wolna encyklopedia
Cyclin-dependent kinase 8Cyclin-dependent kinase 8
Dominance (genetics)Dominance (genetics)
Serine/threonine-specific protein kinaseSerine/threonine-specific protein kinase
NeurodegenerationNeurodegeneration
PRKAG1PRKAG1
mTOR inhibitorsmTOR inhibitors
PolioPolio
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Ataxia TelangiectasiaAtaxia Telangiectasia Mutated ProteinsTelangiectasisTelangiectasia, Hereditary HemorrhagicAtaxiaTumor Suppressor ProteinsCerebellar AtaxiaCell Cycle ProteinsProtein-Serine-Threonine KinasesRetinal TelangiectasisFriedreich AtaxiaDNA-Binding ProteinsDNA DamageSpinocerebellar AtaxiasRadiation, IonizingCheckpoint Kinase 2DNA RepairGait AtaxiaGamma RaysRadiation ToleranceTumor Suppressor Protein p53DNA Breaks, Double-StrandedDNA-Activated Protein KinaseEpistaxisPhosphorylationPyronesActivin Receptors, Type IIArteriovenous MalformationsHistonesNuclear ProteinsFibroblastsMutationDose-Response Relationship, RadiationCell CycleNijmegen Breakage SyndromeStreptonigrinCREST SyndromeCell LineProtein KinasesSignal TransductionG2 PhaseDNA ReplicationChromosome BreakageMicrocephalyUltraviolet RaysHeterozygoteX-RaysChromosome AberrationsApoptosisInfrared RaysGenes, cdcNucleic Acid Synthesis InhibitorsReplication Protein ACell Line, TumorS PhaseCell Line, TransformedDNA Repair EnzymesGenomic InstabilityCell SurvivalCells, CulturedLymphocytesG2 Phase Cell Cycle CheckpointsTelomereAphidicolinTelomeric Repeat Binding Protein 2Mice, KnockoutIron-Binding ProteinsCell Cycle CheckpointsDNAPhenotypeCardiac Output, HighHydroxyureaActivin Receptors, Type IMorpholinesMutation, MissenseComet AssayHeLa CellsChromosome DisordersHomozygoteBleomycinCaffeineAlkylating AgentsCerebellumChromosomes, Human, Pair 11SerineProteinsSyndromeImmunologic Deficiency SyndromesIntracellular Signaling Peptides and ProteinsRNA, Small InterferingMolecular Sequence DataDNA LigasesCell AgingG1 PhaseMice, 129 StrainRNA InterferenceBase SequencePedigreeChromosomal Proteins, Non-HistoneCell NucleusChromosomes, Human, Pair 14BRCA1 ProteinMachado-Joseph DiseaseCyclin-Dependent Kinase Inhibitor p21Oxidative StressChromatinEnzyme ActivationDNA Mutational AnalysisImmunoblottingRetinal DiseasesRecombination, GeneticHCT116 CellsCamptothecinPoly(ADP-ribose) PolymerasesLymphomaBlotting, WesternGene Rearrangement, T-LymphocyteChromosomal InstabilityLeucine ZippersAngiodysplasiaTrinucleotide Repeat Expansioncdc25 PhosphatasesPhosphatidylinositol 3-KinasesTopoisomerase I InhibitorsTranslocation, GeneticModels, BiologicalKaryotypingRadiation-Sensitizing AgentsThreonineMitosisIntracranial Arteriovenous MalformationsProto-Oncogene Proteins c-ablAndrostadienesFlow CytometryProto-Oncogene Proteins c-mdm2Enzyme InhibitorsCell DivisionAllelesProtein BindingGene DeletionTelomeraseMice, Mutant StrainsDown-Regulation
Targeted Mutations in the ATR Pathway Define Agent-Specific Requirements for Cancer Cell Growth and SurvivalTargeted Mutations in the ATR Pathway Define Agent-Specific Requirements for Cancer Cell Growth and Survival
BioDiscovery ATM in focus: A damage sensor and cancer targetBioDiscovery ATM in focus: A damage sensor and cancer target
ATM-dependent phosphorylation of ATF2 is required for the DNA damage response.ATM-dependent phosphorylation of ATF2 is required for the DNA damage response.
Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. - PubMed - NCBIAutophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. - PubMed - NCBI
DNA-Dependent Protein Kinase and Ataxia Telangiectasia Mutated (ATM) Promote Cell Survival in Response to NK314, a...DNA-Dependent Protein Kinase and Ataxia Telangiectasia Mutated (ATM) Promote Cell Survival in Response to NK314, a...
Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related ...Caffeine inhibits checkpoint responses without inhibiting the ataxia-telangiectasia-mutated (ATM) and ATM- and Rad3-related ...
RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 | PNASRAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1 | PNAS
ATM gene: MedlinePlus GeneticsATM gene: MedlinePlus Genetics
IGF and Insulin Receptor Signaling in Breast Cancer | SpringerLinkIGF and Insulin Receptor Signaling in Breast Cancer | SpringerLink
Inhibition of Transforming Growth Factor-β1 Signaling Attenuates Ataxia Telangiectasia Mutated Activity in Response to...Inhibition of Transforming Growth Factor-β1 Signaling Attenuates Ataxia Telangiectasia Mutated Activity in Response to...
Autophosphorylation - WikipediaAutophosphorylation - Wikipedia
MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation | PNASMSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation | PNAS
DIM (3,3-diindolylmethane) confers protection against ionizing radiation by a unique mechanismDIM (3,3'-diindolylmethane) confers protection against ionizing radiation by a unique mechanism
ATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndromeATM-dependent suppression of stress signaling reduces vascular disease in metabolic syndrome
Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR)...Dbf4 is direct downstream target of ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR)...
Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and...Association of Tumor Protein p53 and Ataxia-Telangiectasia Mutated Comutation With Response to Immune Checkpoint Inhibitors and...
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...
The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by...The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by...
Cisplatin-resistant A549 non-small cell lung cancer cells can be identified by increased mitochondrial mass and are sensitive...Cisplatin-resistant A549 non-small cell lung cancer cells can be identified by increased mitochondrial mass and are sensitive...
Frontiers | DNA Damage Response and Autophagy: A Meaningful Partnership | GeneticsFrontiers | DNA Damage Response and Autophagy: A Meaningful Partnership | Genetics
ATM - Serine-protein kinase ATM - Sus scrofa (Pig) - ATM gene & proteinATM - Serine-protein kinase ATM - Sus scrofa (Pig) - ATM gene & protein
A Proteomic Analysis of Arginine-methylated Protein Complexes | Molecular & Cellular ProteomicsA Proteomic Analysis of Arginine-methylated Protein Complexes | Molecular & Cellular Proteomics
STK11 | definition of STK11 by Medical dictionarySTK11 | definition of STK11 by Medical dictionary
Physiology and Pathology of Autoimmune Diseases: Role of CD4+ T cells in Rheumatoid Arthritis | IntechOpenPhysiology and Pathology of Autoimmune Diseases: Role of CD4+ T cells in Rheumatoid Arthritis | IntechOpen
POLD1 | Cancer Genetics WebPOLD1 | Cancer Genetics Web
Resveratrol-induced Activation of p53 and Apoptosis Is Mediated by Extracellular- Signal-regulated Protein Kinases and p38...Resveratrol-induced Activation of p53 and Apoptosis Is Mediated by Extracellular- Signal-regulated Protein Kinases and p38...
Ibrutinib as an Immune Modulating Agent for Patients With Asymptomatic, High-risk CLL/SLL Risk Chronic Lymphocytic Leukemia or...Ibrutinib as an Immune Modulating Agent for Patients With Asymptomatic, High-risk CLL/SLL Risk Chronic Lymphocytic Leukemia or...
Third Row TMs for Treating Cancer | Philosophical Transactions of the Royal Society of London A: Mathematical, Physical and...Third Row TMs for Treating Cancer | Philosophical Transactions of the Royal Society of London A: Mathematical, Physical and...
Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and ...Topoisomerase poisons differentially activate DNA damage checkpoints through ataxia-telangiectasia mutated-dependent and ...
AT - Ataxia-Telangiectasia | AcronymFinderAT - Ataxia-Telangiectasia | AcronymFinder
Reactive oxygen species induce chondrocyte hypertrophy in endochondral ossification | JEMReactive oxygen species induce chondrocyte hypertrophy in endochondral ossification | JEM
Plus itPlus it
Frontiers | Soft TCPTP Agonism-Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine | PharmacologyFrontiers | Soft TCPTP Agonism-Novel Target to Rescue Airway Epithelial Integrity by Exogenous Spermidine | Pharmacology
AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Ataxia TelangiectasiaAtaxia Telangiectasia Mutated ProteinsTelangiectasisTelangiectasia, Hereditary HemorrhagicAtaxiaTumor Suppressor ProteinsCerebellar AtaxiaCell Cycle ProteinsProtein-Serine-Threonine KinasesRetinal TelangiectasisFriedreich AtaxiaDNA-Binding ProteinsDNA DamageSpinocerebellar AtaxiasRadiation, IonizingCheckpoint Kinase 2DNA RepairGait AtaxiaGamma RaysRadiation ToleranceTumor Suppressor Protein p53DNA Breaks, Double-StrandedDNA-Activated Protein KinaseEpistaxisPhosphorylationPyronesActivin Receptors, Type IIArteriovenous MalformationsHistonesNuclear ProteinsFibroblastsMutationDose-Response Relationship, RadiationCell CycleNijmegen Breakage SyndromeStreptonigrinCREST SyndromeCell LineProtein KinasesSignal TransductionG2 PhaseDNA ReplicationChromosome BreakageMicrocephalyUltraviolet RaysHeterozygoteX-RaysChromosome AberrationsApoptosisInfrared RaysGenes, cdcNucleic Acid Synthesis InhibitorsReplication Protein ACell Line, TumorS PhaseCell Line, TransformedDNA Repair EnzymesGenomic InstabilityCell SurvivalCells, CulturedLymphocytesG2 Phase Cell Cycle CheckpointsTelomereAphidicolinTelomeric Repeat Binding Protein 2Mice, KnockoutIron-Binding ProteinsCell Cycle CheckpointsDNAPhenotypeCardiac Output, HighHydroxyureaActivin Receptors, Type IMorpholinesMutation, MissenseComet AssayHeLa CellsChromosome DisordersHomozygoteBleomycinCaffeineAlkylating AgentsCerebellumChromosomes, Human, Pair 11SerineProteinsSyndromeImmunologic Deficiency SyndromesIntracellular Signaling Peptides and ProteinsRNA, Small InterferingMolecular Sequence DataDNA LigasesCell AgingG1 PhaseMice, 129 StrainRNA InterferenceBase SequencePedigreeChromosomal Proteins, Non-HistoneCell NucleusChromosomes, Human, Pair 14BRCA1 ProteinMachado-Joseph DiseaseCyclin-Dependent Kinase Inhibitor p21Oxidative StressChromatinEnzyme ActivationDNA Mutational AnalysisImmunoblottingRetinal DiseasesRecombination, GeneticHCT116 CellsCamptothecinPoly(ADP-ribose) PolymerasesLymphomaBlotting, WesternGene Rearrangement, T-LymphocyteChromosomal InstabilityLeucine ZippersAngiodysplasiaTrinucleotide Repeat Expansioncdc25 PhosphatasesPhosphatidylinositol 3-KinasesTopoisomerase I InhibitorsTranslocation, GeneticModels, BiologicalKaryotypingRadiation-Sensitizing AgentsThreonineMitosisIntracranial Arteriovenous MalformationsProto-Oncogene Proteins c-ablAndrostadienesFlow CytometryProto-Oncogene Proteins c-mdm2Enzyme InhibitorsCell DivisionAllelesProtein BindingGene DeletionTelomeraseMice, Mutant StrainsDown-Regulation
KinaseDistinctKinasesApoptosisABBREVIATIONSRAD3EncodesAntibodyDisease ataxia telangiectasiaSubunitPhosphataseChk2GenesCerebellarAutosomal recessive disorder characterizedAMPKMre11-Rad5RecombinationExpressionSignaling pathwayImmunodeficiencyWorld'sCHK1NuclearSusceptibilityCheckpoint proteinsMultisystem diseaseDownstreamDouble-strandTumor protein p53Western BlotCellularDiseasesMetabolismRadiation sensitivityDamage checkpointCancerOverexpressionInteractsDeficiencyOxidative stressResiduesHuman disorderRegulationDisorderKinase activityPhosphorylatesTranscript
Kinase1
Distinct1
Kinases15
Apoptosis7
ABBREVIATIONS1
RAD311
Encodes6
Antibody2
Disease ataxia telangiectasia3
Subunit7
Phosphatase7
Chk23
Genes2
  • As important genes in the DNA damage response pathway, comutation in the tumor protein p53 (TP53) and ataxia-telangiectasia mutated (ATM) genes may be associated with genomic instability and hypermutation. (cdc.gov)
  • In fact, the dephosphorylating activity of TCPTP inhibits the signaling cascade that leads to the expression of genes involved in detachment and epithelial-to-mesenchymal transition (EMT), and increases the expression of adhesion and tight junction proteins, thereby enhancing the barrier functionality in inflammation-prone tissues. (frontiersin.org)
Cerebellar3
  • Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder characterized by a wide range of clinical manifestations, including cerebellar ataxia, conjunctival telangiectases, recurrent sinopulmonary infections, radiosensitivity, and increased cancer susceptibility (1). (acronymfinder.com)
  • It is a multisystem disease characterized by progressive cerebellar ataxia, oculocutaneous telagiectasia and immunodeficiency with defects in both cellular and humoral immunity. (ebscohost.com)
  • Ataxia telangiectasia (A-T) is a rare autosomal recessive disorder characterized by clinical manifestations that include progressive cerebellar ataxia, neuronal degeneration, hypersensitivity to ionizing radiation (IR), premature aging, hypogonadism, growth retardation, immune deficiency, and an increased risk for cancer ( 1 ). (sciencemag.org)
Autosomal recessive disorder characterized1
AMPK2
Mre11-Rad51
Recombination3
Expression12
Signaling pathway1
  • Studies with rapamycin ( 4 ), a potent immunosuppressant, have uncovered a signaling pathway that modulates protein synthesis in yeast ( 5 ) and animal cells ( 6 , 7 ). (pnas.org)
Immunodeficiency1
World's1
CHK14
Nuclear6
Susceptibility1
Checkpoint proteins1
Multisystem disease1
Downstream2
  • ATM phosphorylates proteins instead of lipid and has many downstream targets that act as cell-cycle regulators including: P53, Mdm2, BRCA1, and SMC1. (fishersci.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)
Double-strand2
Tumor protein p531
Western Blot1
Cellular5
Diseases1
Metabolism1
Radiation sensitivity2
Damage checkpoint1
Cancer14
Overexpression1
Interacts1
Deficiency1
Oxidative stress2
Residues2
Human disorder1
Regulation4
Disorder2
Kinase activity4
  • We determined that loss of TGFβ signaling in epithelial cells truncated ATM autophosphorylation and significantly reduced its kinase activity, without affecting protein abundance. (aacrjournals.org)
  • It has been previously reported that herpes simplex virus type 1 (HSV-1) infection induces activation of protein kinase activity of ATM and hyperphosphorylation of transcription factor, Sp1. (pubfacts.com)
  • Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. (sciencemag.org)
  • Wild-type and mutant recombinant ATM proteins were individually expressed in 293T cells, and in vitro kinase activity was assessed ( 14 ). (sciencemag.org)
Phosphorylates2
Transcript1
NTNU Open: Low expression levels of ATM may substitute for CHEK2/TP53 mutations predicting resistance towards anthracycline and...
NTNU Open: Low expression levels of ATM may substitute for CHEK2/TP53 mutations predicting resistance towards anthracycline and... (ntnuopen.ntnu.no)
ATM (phospho S1981)抗体[10H11.E12]| Abcam中国
ATM (phospho S1981)抗体[10H11.E12]| Abcam中国 (abcam.cn)
ATM gene: MedlinePlus Genetics
ATM gene: MedlinePlus Genetics (medlineplus.gov)
IGF and Insulin Receptor Signaling in Breast Cancer | SpringerLink
IGF and Insulin Receptor Signaling in Breast Cancer | SpringerLink (link.springer.com)
Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer | PNAS
Endogenous DNA double-strand breaks: Production, fidelity of repair, and induction of cancer | PNAS (pnas.org)
Autophosphorylation - Wikipedia
Autophosphorylation - Wikipedia (en.wikipedia.org)
Validation of a high performance functional assay for individual radiosensitivity in pediatric oncology: a prospective cohort...
Validation of a high performance functional assay for individual radiosensitivity in pediatric oncology: a prospective cohort... (link.springer.com)
Frontiers | DNA Damage Response and Autophagy: A Meaningful Partnership | Genetics
Frontiers | DNA Damage Response and Autophagy: A Meaningful Partnership | Genetics (frontiersin.org)
Ibrutinib as an Immune Modulating Agent for Patients With Asymptomatic, High-risk CLL/SLL Risk Chronic Lymphocytic Leukemia or...
Ibrutinib as an Immune Modulating Agent for Patients With Asymptomatic, High-risk CLL/SLL Risk Chronic Lymphocytic Leukemia or... (clinicaltrials.gov)
MRNA Guanylyltransferase Inhibitors - Pipeline Insights, 2017
MRNA Guanylyltransferase Inhibitors - Pipeline Insights, 2017 (researchandmarkets.com)
Phospho-ATM (Ser1981) Mouse anti-Human, Mouse, Clone: 10H11, Invitrogen | Fisher Scientific
Phospho-ATM (Ser1981) Mouse anti-Human, Mouse, Clone: 10H11, Invitrogen | Fisher Scientific (fishersci.com)
Anacardic acid inhibits pancreatic cancer cell growth, and potentiates chemotherapeutic effect by Chmp1A - ATM - p53 signaling...
Anacardic acid inhibits pancreatic cancer cell growth, and potentiates chemotherapeutic effect by Chmp1A - ATM - p53 signaling... (bmccomplementalternmed.biomedcentral.com)
GCN2, an old dog with new tricks | Biochemical Society Transactions
GCN2, an old dog with new tricks | Biochemical Society Transactions (biochemsoctrans.org)
Rfa2 is specifically dephosphorylated by Pph3 in Candida albicans | Biochemical Journal
Rfa2 is specifically dephosphorylated by Pph3 in Candida albicans | Biochemical Journal (biochemj.org)
Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype,...
Pharmacological targeting of the ephrin receptor kinase signalling by GLPG1790 in vitro and in vivo reverts oncophenotype,... (springermedizin.de)
Acute stimulation of glucose influx upon mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR-RAPTOR. | Sigma-Aldrich
Acute stimulation of glucose influx upon mitoenergetic dysfunction requires LKB1, AMPK, Sirt2 and mTOR-RAPTOR. | Sigma-Aldrich (sigmaaldrich.com)
Emerging roles of chromatin in the maintenance of genome organization and function in plants | Genome Biology | Full Text
Emerging roles of chromatin in the maintenance of genome organization and function in plants | Genome Biology | Full Text (genomebiology.biomedcentral.com)