Ataxia telangiectasia mutated proteins. Medical search

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).

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.

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.

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.

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.

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.

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)

Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.

A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.

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.

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)

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.

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.

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)

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.

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.

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.

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.

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.

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.

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.

Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.

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.

Bleeding from the nose.

The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.

Keto-pyrans.

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.

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.

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.

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.

Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.

Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.

The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.

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.

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.

Complex cytotoxic antibiotic obtained from Streptomyces flocculus or S. rufochronmogenus. It is used in advanced carcinoma and causes leukopenia.

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.

Established cell cultures that have the potential to propagate indefinitely.

A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.

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.

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.

The process by which a DNA molecule is duplicated.

A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.

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.)

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.

An individual having different alleles at one or more loci regarding a specific character.

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.

Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.

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.

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 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).

Compounds that inhibit cell production of DNA or RNA.

A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.

A cell line derived from cultured tumor cells.

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.

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.

Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.

An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.

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 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.

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.

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.

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.

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.

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.

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.

Proteins that specifically bind to IRON.

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.

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).

The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.

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.

An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.

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).

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)

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.

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.

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)

An individual in which both alleles at a given locus are identical.

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.

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.

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.

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.

A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.

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.

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.

A characteristic symptom complex.

Syndromes in which there is a deficiency or defect in the mechanisms of immunity, either cellular or humoral.

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.

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.

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.

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).

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.

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.

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.

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.

The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.

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.

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.

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)

A specific pair of GROUP D CHROMOSOMES of the human chromosome classification.

The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)

A 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)

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.

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).

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.

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.

Biochemical identification of mutational changes in a nucleotide sequence.

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.

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.

Human COLORECTAL CARCINOMA cell line.

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.

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.

A general term for various neoplastic diseases of the lymphoid tissue.

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.

Ordered rearrangement of T-cell variable gene regions coding for the antigen receptors.

An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.

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.

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.

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.

A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT 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.

Compounds that inhibit the activity of DNA TOPOISOMERASE I.

A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.

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.

Mapping of the KARYOTYPE of a cell.

Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.

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.

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.

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.

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.

Derivatives of the steroid androstane having two double bonds at any site in any of the rings.

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.

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.

Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.

The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.

Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.

The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.

A 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.

An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.

Mice bearing mutant genes which are phenotypically expressed in the animals.

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)

"Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM". J. Biol. Chem. ... Bloom syndrome protein is a protein that in humans is encoded by the BLM gene and is not expressed in Bloom syndrome. The Bloom ... "Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity". J. Biol. ... "Replication protein A physically interacts with the Bloom's syndrome protein and stimulates its helicase activity". J. Biol. ...

https://en.wikipedia.org/wiki/Bloom_syndrome_protein

... the ataxia telangiectasia mutated ATM kinase, and 53BP1. Because Artemis can remove damaged ends from DNA, it has been proposed ... "Protein Knowledgebase: Gene DCLRE1C - DNA cross-link repair 1C protein (Protein artemis)". Retrieved June 2, 2011. de Villartay ... "Endogenously induced DNA double strand breaks arise in heterochromatic DNA regions and require ataxia telangiectasia mutated ... Artemis is a protein that in humans is encoded by the DCLRE1C (DNA cross-link repair 1C) gene. Artemis is a nuclear protein ...

https://en.wikipedia.org/wiki/Artemis_(protein)

Alpha-synuclein activates ATM (ataxia-telangiectasia mutated), a major DNA damage repair signaling kinase. Alpha-synuclein ... that heat-shock proteins, which assist in refolding proteins susceptible to aggregation, beneficially affect PD when ... The protein alpha-synuclein has increased presence in the brains of Parkinson's Disease patients and, as α-synuclein is ... Protein aggregates or cytokines from neuroinflammation may interfere with cell receptors and alter their function in the BBB. ...

https://en.wikipedia.org/wiki/Pathophysiology_of_Parkinson's_disease

... has been shown to interact with: Ataxia telangiectasia and Rad3 related, Ataxia telangiectasia mutated, HUS1, NHP2L1, ... Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene. The protein encoded by this gene ... This protein binds to chromatin prior to DNA damage and is phosphorylated by ATR after the damage. This protein recruits the ... Rauen M, Burtelow MA, Dufault VM, Karnitz LM (2000). "The human checkpoint protein hRad17 interacts with the PCNA-like proteins ...

https://en.wikipedia.org/wiki/RAD17

... protein and the ATM (ataxia telangiectasia mutated) protein. ATM is thought to be a master controller of cell cycle checkpoint ... BRCA1-associated ATM activator 1 is a protein in humans that is encoded by the BRAT1 gene. The protein encoded by this ... The protein encoded by this gene is thought to play a role in the DNA damage pathway regulated by BRCA1 and ATM. GRCh38: ... Human proteins, All stub articles, Human chromosome 7 gene stubs). ...

https://en.wikipedia.org/wiki/BRAT1

It is composed of ataxia telangiectasia mutated (ATM), ataxia telangiectasia and Rad3 related (ATR), DNA-dependent protein ... Many of these functions relate to the ability of class I PI3Ks to activate protein kinase B (PKB, aka Akt) as in the PI3K/AKT/ ... The class IA PI3K p110α is mutated in many cancers. Many of these mutations cause the kinase to be more active. It is the ... Many other proteins have been identified that are regulated by PtdIns(3,4,5)P3, including Bruton's tyrosine kinase (BTK), ...

https://en.wikipedia.org/wiki/Phosphoinositide_3-kinase

Ataxia telangiectasia mutated, BARD1, BRCA1, BRCA2, BRCC3, BRE, Bloom syndrome protein, DMC1, RAD54, P53 RAD52, RAD54B, and ... DNA repair protein RAD51 homolog 1 is a protein encoded by the gene RAD51. The enzyme encoded by this gene is a member of the ... This protein can interact with the ssDNA-binding protein RPA, BRCA2, PALB2 and RAD52. The structural basis for Rad51 filament ... Seitz EM, Brockman JP, Sandler SJ, Clark AJ, Kowalczykowski SC (May 1998). "RadA protein is an archaeal RecA protein homolog ...

https://en.wikipedia.org/wiki/RAD51

... protein and ATM (ataxia-telangiectasia mutated) serine/threonine kinase weakens with age in oocytes of numerous species ...

https://en.wikipedia.org/wiki/Age_and_female_fertility

Ataxia telangiectasia mutated) and ATR (Ataxia telangiectasia and Rad3 related), and the microtubule-binding protein XMAP215/ ... a type of solenoid protein domain found in a number of cytoplasmic proteins. The name "HEAT" is an acronym for four proteins in ... DNA-dependent protein kinase) Fanconi anemia responsible protein FANCF (FANCF) Damaged DNA-binding protein AlkD (Alkylpurin DNA ... The nuclear transport protein importin beta contains 19 HEAT repeats. Representative examples of HEAT repeat proteins include ...

https://en.wikipedia.org/wiki/HEAT_repeat

... protein kinase C (PKC), ataxia telangiectasia mutated kinase (ATM), cyclin-dependent kinase 5 (CDK5), and casein kinase 1 (CK1 ... "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2017-05-07. "Human BLAT ... "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2017-05-06. (All articles ... The relatively fast rate of change in LENG9 compared to that of other proteins suggests that the gene is adaptive for vital ...

https://en.wikipedia.org/wiki/LENG9

Ataxia telangiectasia mutated (ATM) Ataxia telangiectasia and Rad3 related (ATR) 5' AMP-activated protein kinase (AMPK) RAF ... 5' adenosine-monophosphate-activated protein kinase (AMPK) has also been found to be an effector for RHEB. AMPK is a protein ... The protein is a lipid-anchored, cell-membrane protein with five repeats of the RAS-related GTP-binding region. Also present ... encodes a protein that activates apoptosis and interacts selectively with survival-promoting proteins Bcl-2 and Bcl-X(L)". The ...

https://en.wikipedia.org/wiki/RHEB

Ataxia telangiectasia mutated) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved ... In E. coli , the proteins involved are the Mut class proteins: MutS, MutL, and MutH. In most Eukaryotes, the analog for MutS is ... These proteins seem to be required for transmitting the checkpoint activation signal to downstream proteins. DNA damage ... Checkpoint Proteins can be separated into four groups: phosphatidylinositol 3-kinase (PI3K)-like protein kinase, proliferating ...

https://en.wikipedia.org/wiki/DNA_repair

... apolipoprotein A-IV ARCN1 encoding protein Archain 1 ASRGL1: encoding enzyme L-asparaginase ATM: ataxia telangiectasia mutated ... encoding protein Uncharacterized protein C11orf16 C11orf49: encoding protein UPF0705 protein C11orf49 C11orf52 encoding protein ... encoding protein Acrosomal protein SP-10 AKIP1: A kinase interacting protein 1 ALKBH3 encoding protein AlkB homolog 3, alpha- ... encoding protein C1q and tumor necrosis factor related protein 5 CAPRIN1: encoding protein, cell cycle associated protein 1 ...

https://en.wikipedia.org/wiki/Chromosome_11

... and ataxia telangiectasia-mutated (ATM) most involved in repairing DSBs to the more versatile Rad3-related (ATR). ATR is ... Proteins such as "damage-up" proteins (DDPs) can promote endogenous DNA lesions by either increasing the amount of reactive ... Next, further protein-protein interactions and posttranslational modifications (PTMs) complete the kinase activation, and a ... These three DDR kinases all recognize damage via protein-protein interactions which localize the kinases to the areas of damage ...

https://en.wikipedia.org/wiki/Molecular_lesion

Alpha-synuclein activates ataxia telangiectasia mutated, a major DNA damage-repair signaling kinase. In addition, alpha- ... At the same time, regimens for PD restrict proteins during breakfast and lunch, allowing protein intake in the evening. PD ... Levodopa and proteins use the same transportation system in the intestine and the blood-brain barrier, thereby competing for ... The cause of this cell death is poorly understood, but involves the build-up of misfolded proteins into Lewy bodies in the ...

https://en.wikipedia.org/wiki/Parkinson's_disease

A similar mechanism involves the ataxia telangiectasia mutated (ATM) serine/threonine kinase which is an enzyme involved in the ... The NF- κB proteins interact with IκB inhibitory proteins, but during oxidative stress IκB proteins are degraded in the cell. ... The loss of IκB proteins for NF- κB proteins to bind to results in NF- κB proteins entering the nucleus to bind to specific ... The production of ROS in high quantity in cells results in the degradation of biomolecules such as proteins, DNA, and RNA. In ...

https://en.wikipedia.org/wiki/Biological_effects_of_radiation_on_the_epigenome

At a DSB, MRE11-RAD50-NBS1 (MRN) protein complex recruits ataxia telangiectasia mutated (ATM) kinase which phosphorylates ... HMGA2 protein specifically targets the promoter of ERCC1, thus reducing expression of this DNA repair gene. ERCC1 protein ... HGMA proteins are polypeptides of ~100 amino acid residues characterized by a modular sequence organization. These proteins ... April 2003). "Negative regulation of BRCA1 gene expression by HMGA1 proteins accounts for the reduced BRCA1 protein levels in ...

https://en.wikipedia.org/wiki/Cancer_epigenetics

Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and ... Chen J (September 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following ... A mutated BRCA1 gene usually makes a protein that does not function properly. Researchers believe that the defective BRCA1 ... A protein called valosin-containing protein (VCP, also known as p97) plays a role to recruit BRCA1 to the damaged DNA sites. ...

https://en.wikipedia.org/wiki/BRCA1

Serine/threonine-protein kinase ATR also known as ataxia telangiectasia and Rad3-related protein (ATR) or FRAP-related protein ... Gatei M, Zhou BB, Hobson K, Scott S, Young D, Khanna KK (May 2001). "Ataxia telangiectasia mutated (ATM) kinase and ATM and ... Ataxia telangiectasia and Rad3-related protein has been shown to interact with: BRCA1, CHD4, HDAC2, MSH2, P53 RAD17, and RHEB. ... Chen J (September 2000). "Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following ...

https://en.wikipedia.org/wiki/Ataxia_telangiectasia_and_Rad3_related

... has been shown to interact with Mdm2 and Ataxia telangiectasia mutated. Abnormalities in this gene are one of the causes ... "Mammalian p53R2 protein forms an active ribonucleotide reductase in vitro with the R1 protein, which is expressed both in ... "Wild-type p53 regulates human ribonucleotide reductase by protein-protein interaction with p53R2 as well as hRRM2 subunits". ... The gene encoding the RRM2B protein is located on chromosome 8, at position 8q23.1. The gene and its products are also known by ...

https://en.wikipedia.org/wiki/RRM2B

In the presence of ionizing radiation (IR), the Smc1 subunit of cohesin is phosphorylated by the ataxia telangiectasia mutated ... This alternative form is composed of core RFC proteins RFC2, RFC3, RFC4, and RFC5, but replaces the RFC1 protein with cohesion ... SMC1ß, REC8 and STAG3 are meiosis specific cohesin proteins. The STAG3 protein is essential for female meiosis and fertility. ... The cohesin ring is composed of two SMC (structural maintenance of chromosomes) proteins and two additional Scc proteins. ...

https://en.wikipedia.org/wiki/Establishment_of_sister_chromatid_cohesion

... has been shown to interact with: Ataxia telangiectasia mutated, BRCA1, H2AFX, MRE11A, Rad50, and TERF2 GRCh38: Ensembl ... Nibrin, also known as NBN or NBS1, is a protein which in humans is encoded by the NBN gene. Nibrin is a protein associated with ... The central role is carried out by ataxia telangiectasia mutated (ATM) by activating the DSB signaling cascade, phosphorylating ... ICP8, which is a viral single-strand binding protein, is known to interact with several DNA repair proteins, such as Rad50, ...

https://en.wikipedia.org/wiki/Nibrin

... a protein), MAPRE2 (Microtubule-associated protein RP/EB, a protein), ATM (Ataxia telangiectasia mutated, a protein kinase), ... TERF1 has been shown to interact with: Abl gene, Ataxia telangiectasia mutated, MAPRE1, NME1, PINX1 SALL1, TINF2, TNKS2, and ... the protein has other functions. These functions include the binding of the protein, facilitation in the activity of protein ... The protein has the ultimate use of functioning as an inhibitor of telomerase, a protein enzyme that assists in the elongation ...

https://en.wikipedia.org/wiki/Telomeric_repeat-binding_factor_1

December 1999). "The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like ... By itself, the protein has 3' to 5' exonuclease activity and endonuclease activity. The protein forms a complex with the RAD50 ... In this organism the Mre11 protein interacts with the Rad50 protein and appears to have an active role in the repair of DNA ... Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the MRE11 gene. The gene has been designated ...

https://en.wikipedia.org/wiki/MRE11A

Ataxia telangiectasia mutated (ATM) is a kinase that (similar to mTOR) can phosphorylate KAP1 resulting in the switch from ... KRAB-associated protein-1), is a protein that in humans is encoded by the TRIM28 gene. The protein encoded by this gene ... The protein localizes to the nucleus and is thought to associate with specific chromatin regions. The protein is a member of ... "KAP-1 corepressor protein interacts and colocalizes with heterochromatic and euchromatic HP1 proteins: a potential role for ...

https://en.wikipedia.org/wiki/TRIM28

Ataxia telangiectasia mutated (ATM) activates after a larger amount of DSBs is detected at later stages of DNA re-replication. ... Once bound to chromatin the ORC recruits the AAA+ ATPase Cdc6 and the coiled-coil domain protein Cdt1. Cdt1 binding and the ... Ataxia telangiectasia and Rad3 related (ATR) is activated earlier when it detects ssDNA in the earlier phases of DNA re- ... Replication initiation proteins are overexpressed in tissue samples from several types of human cancers and experimental ...

https://en.wikipedia.org/wiki/DNA_re-replication

... increased phosphorylation of ataxia telangiectasia mutated (ATM), checkpoint kinase 1 (Chk 1), Chk 2; and reduced cell division ... causing oxidized protein levels to increase. This led researchers to conclude that oxidation of cellular proteins is ... as well as inhibiting pore-destabilizing proteins (Bcl-2-associated X protein, Bcl-2 homologous antagonist/killer). The ... The altered protein expression in neurons, controlled in part by ROS-dependent demethylation of CpG sites in gene promoters ...

https://en.wikipedia.org/wiki/Reactive_oxygen_species

April 2000). "Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase ... The CHEK2 protein encoded by the CHEK2 gene is a serine threonine kinase. The protein consists of 543 amino acids and the ... Furthermore, the CHK2 protein interacts with several other proteins including p53 (p53). Stabilization of p53 by CHK2 leads to ... ataxia-telangiectasia and Rad3 related) kinase that responds primarily to single-strand breaks. In mice, CHEK2 is essential for ...

https://en.wikipedia.org/wiki/CHEK2

The presence of DNA damage triggers the ATM (Ataxia telangiectasia mutated) or ATR (Ataxia Telangiectasia and Rad3 related) ... The cell cycle is driven by proteins called cyclin dependent kinases that associate with cyclin regulatory proteins at ... One such protein is rad18 that is required for G2 arrest even when Chk1 is phosphorylated and active. Thus, rad18 is required ... Proteins that localize to sites of DNA damage in the G2 phase initiate a signaling cascade that regulates important components ...

https://en.wikipedia.org/wiki/G2-M_DNA_damage_checkpoint

She found that a mutation in ataxia telangiectasia mutated kinase (ATM) causes damage to DNA and chromatin structure. Jeggo's ... In her most recent publication, Jeggo worked with other researchers on the Ataxia telangiectasia and Rad3 related protein (ATR ... "A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome". ... "The Ataxia-Telangiectasia Society Annual Report and Accounts" (PDF). 2014. "Information for ICRR2015". Journal of Radiation ...

https://en.wikipedia.org/wiki/Penelope_Jeggo

These include ataxia-telangiectasia, Nijmegen breakage syndrome, some subgroups of xeroderma pigmentosum, trichothiodystrophy, ... Protein synthesis and protein degradation decline with age in skeletal and heart muscle, as would be expected, since DNA damage ... The cell will die in the next mitosis or in some rare instances, mutate." In tissues composed of non- or infrequently ... found numerous changes in protein expression in rat skeletal muscle with age, including lower levels of several proteins ...

https://en.wikipedia.org/wiki/DNA_damage_theory_of_aging

Premature aging syndromes including Werner syndrome, Progeria, Ataxia telangiectasia, Ataxia-telangiectasia like disorder, ... the time to senescence can be extended by inactivating the tumor suppressor proteins - p53 and Retinoblastoma protein (pRb). ... However, the genes that have mutated in these diseases all have roles in the repair of DNA damage and the increased DNA damage ... TERT proteins from many eukaryotes have been sequenced. By using TERC, TERT can add a six-nucleotide repeating sequence, 5'- ...

https://en.wikipedia.org/wiki/Telomerase

Arthrogryposis-renal dysfunction-cholestasis syndrome Ataxia telangiectasia (Louis-Bar syndrome) Atrichia with papular lesions ... by problems with junctional proteins List of dental abnormalities associated with cutaneous conditions List of genes mutated in ... Telangiectasia Telangiectasia macularis eruptiva perstans Teratoma Tufted angioma (acquired tufted angioma, angioblastoma, ... Food-induced purpura Generalized essential telangiectasia (general essential telangiectasia) Giant-cell arteritis Gougerot-Blum ...

https://en.wikipedia.org/wiki/List_of_skin_conditions

Ataxia telangiectasia mutated) or ATR (Ataxia Telangiectasia and Rad3 related), which act as sensors, depending on the type of ... The third pocket protein, Rb, binds to and represses E2F 1, E2F 2, and E2F 3, which are the E2F proteins with activating ... It was additionally shown that blocking Mos protein synthesis makes the MAPK-P responses more graded, showing that Mos protein ... The latter is a protein whose function is to inhibit separase, which in turn cuts the cohesins, the protein composite ...

https://en.wikipedia.org/wiki/Cell_cycle_checkpoint

Ataxia-telangiectasia Bloom syndrome BRCA1 & BRCA2 Fanconi anemia Familial adenomatous polyposis Hereditary breast and ovarian ... In many cases, genetic testing can be used to identify mutated genes or chromosomes that are passed through generations. Gene ... Insulin-like growth factors and their binding proteins play a key role in cancer cell growth, differentiation and apoptosis, ... current understanding regarding the mechanism of cancer development in obesity relates to abnormal levels of metabolic proteins ...

https://en.wikipedia.org/wiki/Causes_of_cancer

... ataxia telangiectasia. EZH2 is the catalytic subunit of the Polycomb Repressive Complex 2 (PRC2). EZH2's catalytic activity ... In particular, WD40-repeat protein embryonic ectoderm development (EED) and zinc finger protein suppressor of zeste 12 (SUZ12) ... The histidine residue in the active site of the wild-type EZH2 was mutated to tyrosine in patients diagnosed with Weaver ... Dillon SC, Zhang X, Trievel RC, Cheng X (2005). "The SET-domain protein superfamily: protein lysine methyltransferases". Genome ...

https://en.wikipedia.org/wiki/EZH2

Four (ataxia-telangiectasia, ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome and Alzheimer's disease) are ... less than one mutated protein per generation). Sometimes, in a species with a stable karyotype, random variations that modify ... Four of them (Huntington's disease, various spinocerebellar ataxias, Friedreich's ataxia and myotonic dystrophy types 1 and 2) ... Friedrich's ataxia, and Huntington's disease, most of which are caused by expansion of repeats at the DNA, RNA, or protein ...

https://en.wikipedia.org/wiki/Genome_instability

... such as ataxia telangiectasia, BRCA1 inherited breast and ovarian cancer, Nbs1 Nijmegen breakage syndrome, RecQL4 Rothmund- ... tropicalis to probe the function of a protein by observing the results of eliminating the protein's activity. For example, a ... The mechanism of action for several genes mutated in human cystic kidney disorders (e.g. nephronophthisis) have been ... Sobeck A, Stone S, Landais I, de Graaf B, Hoatlin ME (September 2009). "The Fanconi anemia protein FANCM is controlled by ...

https://en.wikipedia.org/wiki/Xenopus

Castillo P, Bogliolo M, Surralles J (2011). "Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in ... that is detected by the FANCM protein. Following assembly, the protein core complex activates FANCL protein which acts as an E3 ... About 2% of FA cases are X-linked recessive, which means that if the mother carries one mutated Fanconi anemia allele on one X ... Recent studies have shown that eight of these proteins, FANCA, -B, -C, -E, -F, -G, -L and -M, assemble to form a core protein ...

https://en.wikipedia.org/wiki/Fanconi_anemia

... immune response transcription factor relish is necessary for neurodegeneration in a Drosophila model of ataxia-telangiectasia ... This protein makes the female reluctant to copulate for about 10 days after insemination. The signal pathway leading to this ... such as to identify genes purported to increase lifespan when mutated. D. melanogaster is also used in studies of aging. Werner ... It is caused by mutations in the gene WRN that encodes a protein with essential roles in repair of DNA damage. Mutations in the ...

https://en.wikipedia.org/wiki/Drosophila_melanogaster

... ataxia telangiectasia, the radiosensitive forms of severe combined immunodeficiency disease (SCID), the autoimmune ... The NK cells expression relatively high levels of the LMP1 viral protein; this protein may activate the NF-κB cell signaling ... MYC is a proto-oncogene (i.e. a cancer-causing gene if appropriately mutated or overexpressed) located on the long ("q") arm of ... and other viral proteins; in >50% of cases, they also express classic B cell antigenic proteins such as CD20, BCL6, and CD15. ...

https://en.wikipedia.org/wiki/Epstein–Barr_virus–associated_lymphoproliferative_diseases

"Functional characterization connects individual patient mutations in ataxia telangiectasia mutated (ATM) with dysfunction of ... The protein produced by the TP53 gene, p53, is involved in cell cycle arrest, DNA repair and apoptosis. Defective p53 may not ... Examples of autosomal recessive cancer syndromes are ataxia-telangiectasia, Bloom syndrome, Fanconi anemia, MUTYH-associated ... The cause of this disorder is a mutated APC gene, which is involved in β-catenin regulation. Faulty APC causes β-catenin to ...

https://en.wikipedia.org/wiki/Cancer_syndrome

In Niemann-Pick type C, the protein product of the major mutated gene NPC1 is not an enzyme but appears to function as a ... "N-Acetyl-L-Leucine for Ataxia-Telangiectasia". clinicaltrials.gov. Retrieved 2019-08-01. "IntraBio". Retrieved 2019-08-01. ... and Ataxia-Telangiectasia. Future opportunities to develop N-Acetyl-Leucine include Lewy body dementia, amyotrophic lateral ... The protein coded by the NPC2 gene more closely resembles an enzyme structurally but seems to act in cooperation with the NPC1 ...

https://en.wikipedia.org/wiki/Niemann–Pick_disease,_type_C

... autosomal recessive ataxia-telangiectasia and autosomal dominantly inherited mutations in the BRCA2 and PALB2 genes; hereditary ... Four genes have each been found to be mutated in the majority of adenocarcinomas: KRAS (in 95% of cases), CDKN2A (also in 95 ... This is also true of protein-bound paclitaxel (nab-paclitaxel), which was licensed by the FDA in 2013 for use with gemcitabine ... The genes often found mutated in PanNETs are different from those in exocrine pancreatic cancer. For example, KRAS mutation is ...

https://en.wikipedia.org/wiki/Pancreatic_cancer

"53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response ... This protein also goes by the name Nuclear Factor with BRCT Domain 1 (NFBD1). The MDC1 gene encodes the MDC1 nuclear protein ... The MDC1s role in DDR is to function both as a mediator/adaptor protein mediating a complex of other DDR proteins at the site ... Mediator of DNA damage checkpoint protein 1 is a 2080 amino acid long protein that in humans is encoded by the MDC1 gene ...

https://en.wikipedia.org/wiki/MDC1

... has been shown to interact with: FANCI Ataxia telangiectasia mutated, BARD1, BRCA1. BRCA2, FANCE, HTATIP, and MEN1. ... This protein is monoubiquitinated in response to DNA damage, resulting in its localization to nuclear foci with other proteins ... Castillo P, Bogliolo M, Surralles J (May 2011). "Coordinated action of the Fanconi anemia and ataxia telangiectasia pathways in ... May 2002). "Convergence of the fanconi anemia and ataxia telangiectasia signaling pathways". Cell. 109 (4): 459-72. doi:10.1016 ...

https://en.wikipedia.org/wiki/FANCD2

"The gene mutated in ataxia-ocular apraxia 1 encodes the new HIT/Zn-finger protein aprataxin". Nat Genet. 29 (2): 189-93. doi: ... 1989). "Ataxia-ocular motor apraxia: a syndrome mimicking ataxia-telangiectasia". Ann. Neurol. 24 (4): 497-502. doi:10.1002/ana ... 2004). "Aprataxin, the causative protein for EAOH is a nuclear protein with a potential role as a DNA repair protein". Ann. ... The encoded protein may play a role in single-stranded DNA repair. Mutations in this gene have been associated with ataxia- ...

https://en.wikipedia.org/wiki/Aprataxin

Ataxia Telangiectasia Mutated Proteins * Protein Serine-Threonine Kinases * TEL1 protein, S cerevisiae ... The protein kinases ATM and ATR, as well as their budding yeast orthologs Tel1 and Mec1, act as master regulators of the DDR. ... The initiating events in the DDR entail both DNA lesion recognition and assembly of protein complexes at the damaged DNA sites ...

https://pubmed.ncbi.nlm.nih.gov/32219379/

The ATM gene provides instructions for making a protein that helps control the rate at which cells grow and divide. Learn about ... ataxia telangiectasia mutated. *ATM_HUMAN. *human phosphatidylinositol 3-kinase homolog. *serine-protein kinase ATM ... Hall J. The Ataxia-telangiectasia mutated gene and breast cancer: gene expression profiles and sequence variants. Cancer Lett. ... Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. Hum Mol Genet. 2006 Apr 1;15(7):1181-6. doi: ...

https://medlineplus.gov/genetics/gene/atm/

Serine-protein Kinase ATM, Ataxia Telangiectasia Mutated, A-T Mutated)[ATM] ... Order ATM phosphorylated Ser1981 Serine-protein Kinase ATM Ataxia Telangiectasia Mutated A-T Mutated ATM 02015407714 at Gentaur ... ATM, phosphorylated (Ser1981) (Serine-protein Kinase ATM, Ataxia Telangiectasia Mutated, A-T Mutated)[ATM] ... ɑ-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH+ 3 form ...

http://at-gen.com/catalog/1959-mybiosource/3449-atm-phosphorylated-ser1981-serine-protein-kinase-atm-ataxia-telangiectasia-mutated-a-t-mutated-atm

ATM: the Ataxia-Telangiectasia Mutated gene can cause neurodegenerative disorders when it mutates. ... This gene is responsible for creating a protein named tumor protein p53, hence the name TP53. While by name, the protein p53 is ... A gene may mutate because of aging or through mutagens such as radiation. If one inherits a mutated gene, the gene can lose its ... However, if the other gene mutates throughout their lifetime, the cells containing the two mutated BRCA genes become cancer ...

https://www.newhopemedicalcenter.com/blogs/genetics-of-breast-cancer-risk-genes-according-to-recent-studies/

ATM (ataxia telangiectasia mutated) regulates DNA damage response via the PI3K-like protein kinase pathway. Olaparib. [15]. ... BRIP1 (BRCA1-interacting protein 1) functions in DNA repair. Olaparib. BTK. BTK (Brutons tyrosine kinase) regulates B-cell ... PTCH1 (Protein patched homolog 1) is a receptor for Sonic hedgehog (Shh) for gene transcription. Vismodegib, Sonidegib. [33]. ... TP53 (Tumor protein p53) is a tumor suppressor; loss leads to overexpression of VEGF levels. Bevacizumab, Pazopanib. Wee-1 inh ...

https://www.mdpi.com/2072-6694/11/1/11

Researcher received a $423,485 grant to identify the link between a protein called ATM, or ataxia telangiectasia mutated kinase ...

https://www.medindia.net/news/hypertensive-women-with-physically-demanding-jobs-at-higher-risk-of-heart-disease-157780-1.htm

We have shown that nitric oxide limits ataxia-telangiectasia mutated signaling by inhibiting mitochondrial oxidative metabolism ... ataxia-telangiectasia and Rad3-related protein (ATR). In β-cells and non-β-cells, nitric oxide activates ATR signaling by ... Iron regulatory proteins (IRP) 1 and 2 are RNA-binding proteins that regulate intracellular iron homeostasis. IRPs bind to the ... Here, we identified a novel SR-B1-interacting protein, GIPC1 (GAIP-interacting protein, C terminus 1) that interacts with SR-B1 ...

https://www.jbc.org/Metabolism?startPage=0&pageSize=100

Ataxia Telangiectasia and RAD3-related (ATR), and Ataxia Telangiectasia Mutated (ATM) (Richard et al., 2008). Hypoxia has been ... Similarly, hypoxia suppresses the expression of zinc-finger protein ATMIN, which is involved in BER (Jurado et al., 2010), ... Tumors with mutated HR genes, BRCA1 and BRCA2, harbor lower HRR capacity and are more sensitive to Poly (ADP-ribose) polymerase ... If this is the case, hypoxic tumors with mutated HRR genes would be predicted to be hypersensitive to PARPi, resulting in ...

https://www.frontiersin.org/articles/10.3389/fcell.2021.626229/full

... in the vicinity of transcriptionally active genes through multilayered processes instigated by Ataxia telangiectasia mutated ( ... and chromatin regulatory protein complexes, has inspired the field to identify and act upon the full compendium of therapeutic ... ATM), DNA-dependent protein kinase (DNA-PK), and poly-(ADP-ribose) polymerase 1 (PARP1). Novel factors have been identified ...

https://www.cell.com/trends/genetics/issue?pii=S0168-9525%2819%29X0013-X

... ataxia-telangiectasia-mutated kinase (ATM), and ATM- and Rad3-related protein. Premature senescence of balding DPC in vitro in ... pRb and nuclear expression of markers of oxidative stress and DNA damage including heat shock protein-27, super oxide dismutase ...

https://www.researchgate.net/publication/226110618_Hormone_und_Haarwachstum

Abbreviations used in this paper: ATM, ataxia telangiectasia mutated; ATR, ATM and Rad3 related; BP1, binding protein 1; Chk1, ... Abbreviations used in this paper: ATM, ataxia telangiectasia mutated; ATR, ATM and Rad3 related; BP1, binding protein 1; Chk1, ... 3, D-G). In contrast to the Chk1 phosphorylation performed by the ataxia telangiectasia mutated (ATM) and Rad3 related (ATR) ... Chk1 complements the G2/M checkpoint defect and radiosensitivity of ataxia-telangiectasia cells. Oncogene. ...

https://rupress.org/jcb/article/178/7/1101/44902/Global-chromatin-compaction-limits-the-strength-of

Replication Protein A (RPA) is a single stranded DNA binding protein involved in many functions of DNA metabolism, such as DNA ... ataxia telangiectasia mutated), ATR (ATM and Rad3-related) and DNA-PK (DNA-dependent protein kinase) [15]. RPA-3 is thought to ... DNA-binding proteins Is the Subject Area "DNA-binding proteins" applicable to this article? Yes. No. ... Recombinant proteins are in fact TcRPA-1 and TcRPA-2.. Obtained purified recombinant proteins (S1 Fig) were subjected to gel ...

https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0005181

Radioresistant malignant myoepithelioma of the breast with high level of ataxia telangiectasia mutated protein, Journal of ...

https://www.unsw.edu.au/staff/veli-matti-marjoniemi

... and this effect depends on the activity of the ataxia telangiectasia mutated (ATM) serine/threonine protein kinase [2], a DNA ... bound to the RBD-GST fusion protein (RhoA binding domain of the Rhotekin protein, kindly donated by Gary M. Bokoch, The Scripps ... For Western blotting, HeLa cells were lysed with RIPA buffer (see Section 2.4), and 50 μg of protein was mixed with Laemmli ... Chk1/Chk2 protein kinases are activated in response to DNA damage and are involved in DNA damage repair [29]. Pharmacological ...

https://www.hindawi.com/journals/omcl/2016/6012642/

The DNA damage kinase ataxia telangiectasia mutated (ATM) phosphorylates TAOs in vitro; radiation induces phosphorylation of ... TAO on a consensus site for phosphorylation by the ATM protein kinase in cells; and TAO and p38 activation is compromised in ... cells from a patient with ataxia telangiectasia that lack ATM. These findings indicate that TAO kinases are regulators of p38- ...

https://go.drugbank.com/articles/A136081

... as well a delay in the nucleoshuttling of the pATM protein were common features to patients with RT toxicity. We aim to ... Phosphorylated isoform of ataxia telangiectasia mutated (ATM) protein. ROC:. Receiver operating characteristic ... Kinetic data on other DSB repair proteins are collected in order to refine the classification of IRS as secondary endpoints. ... Influence of Nucleoshuttling of the ATM protein in the healthy tissues response to radiation therapy: toward a molecular ...

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-018-4652-7

In human cells in presence of DNA damage Chk2 kinase protein is activated by ATM, the protein mutated in ataxia telangiectasia ... Analysis of Chk2, ATM, NBS1, three proteins involved in the cellular response to DNA damage ... Normal lymphoblastoid cells were exposed to different DNA damaging agents and proteins modifications and activation were ... but not by a deletion mutant encoding for a protein unable to form a complex with Mre11 and Rad50 in the nucleus. These results ...

https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.791534

Ataxia telangiectasia mutated) and ATR (Ataxia- and Rad-related) kinases, whose sequence and functions have been well conserved ... In E. coli , the proteins involved are the Mut class proteins: MutS, MutL, and MutH. In most Eukaryotes, the analog for MutS is ... Ataxia telangiectasia: sensitivity to ionizing radiation and some chemical agents. All of the above diseases are often called " ... A class of checkpoint mediator proteins including BRCA1, MDC1, and 53BP1 has also been identified.[55] These proteins seem to ...

https://en.m.wikipedia.org/wiki/DNA_repair

The Mre11-Rad50-Nbs1 complex acts both upstream and downstream of ataxia telangiectasia mutated and Rad3-related protein (ATR) ... GTP binding; protein binding Genetically amplified in melanoma PPP1R12C Protein phosphatase 1, regulatory subunit 12A/B/C, ... GTP binding; protein binding Genetically amplified in melanoma PPP1R12C Protein phosphatase 1, regulatory subunit 12A/B/C, ... S3C). Still other studies have identified NBS1 as a protein that is a downstream target of ATR (37) that can modulate DNA ...

https://aacrjournals.org/cancerres/article/72/21/5516/575978/RhoJ-Regulates-Melanoma-Chemoresistance-by?searchresult=1

... cerebellar ataxia, variable immunodeficiency with susceptibility to sinopulmonary infections, impaired organ maturation, x-ray ... Ataxia-telangiectasia (A-T) is an autosomal recessive, complex, multisystem disorder characterized by progressive neurologic ... hypersensitivity, ocular and cutaneous telangiectasia (see image below), and a p... ... Xing J, Wu X, Vaporciyan AA, Spitz MR, Gu J. Prognostic significance of ataxia-telangiectasia mutated, DNA-dependent protein ...

https://www.medscape.com/answers/1113394-189642/which-physical-findings-are-characteristic-of-ataxia-telangiectasia-a-t

... or ataxia telangiectasia mutated (ATM) genes.. Unlike the DNA repair proteins, BRCA1 and BRCA2, ATMs role is as a DNA damage ...

https://www.pharmaceutical-technology.com/comment/prostate-cancer-biomarkers/

... ataxia telangiectasia mutated/ataxia telangiectasia and Rad3-related) and CHK1/2 (checkpoint kinase1/2) which in turn activates ... has been shown to interact with the cell cycle checkpoint proteins ATR, CHK1 and ATRIP (ATR-interacting protein). This ... CRY and BMAL1 proteins decreasing their stability and critically regulating the time of action of clock proteins. Similarly, ... and adenosine monophosphate-activated protein kinase (AMPK) are critical factors that regulate the core circadian protein ...

https://www.jcircadianrhythms.com/articles/10.1186/1740-3391-8-3/

Ataxia telangiectasia mutated (ATM), ATM- and Rad3-related protein (ATR) and DNA-dependent protein kinase catalytic subunit ( ... 2007) Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double ... 1999) The ataxia-telangiectasia related protein ATR mediates DNA-dependent phosphorylation of p53 Oncogene 18:3989-3995. ... 2004) Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM ...

https://elifesciences.org/articles/51466v2

Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ... The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01. Graves, P. R., Yu, L., ... A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage. Brown, A. L., Lee ... Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation. Schwarz, J. K., Lovly, C. M. ...

https://profiles.wustl.edu/en/persons/julie-schwarz/publications/?page=2

... ataxia telangiectasia mutated) gene. There is no specific treatment, but clinical management has advanced resulting in longer ... Background Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder caused by variants of ATM ( ... ataxia telangiectasia mutated) gene encoded on chromosome 11q22-23, which causes failure of the ATM protein, a serine/threonine ... Recessive mutations in the cancer gene Ataxia Telangiectasia Mutated (ATM), at a locus previously associated with metformin ...

https://www.researchsquare.com/article/rs-154838/v1

AKT: Protein kinase B. ALDH1: Aldehyde dehydrogenase 1. AT: Ataxia telangiectasia. ATM: Ataxia telangiectasia mutated ... Ataxia telangiectasia and Rad3 related (ATR), and Ataxia telangiectasia mutated (ATM) opens another possibility for the ... Mutations in ATM, a critical DNA repair protein, lead to Ataxia Telangiectasia (AT). As mentioned above, ATM is a serine/ ... The Ku proteins recognize and bind to the damaged site and activate the protein kinase DNA-PKcs, leading to recruitment and ...

https://www.intechopen.com/chapters/48189

Ataxia Telangiectasia Mutated Proteins Entry term(s). A T Protein A-T Protein AT Mutated Protein ATM Protein Mutated Protein, ... A T Protein. A-T Protein. AT Mutated Protein. ATM Protein. Mutated Protein, AT. Protein, A-T. Protein, AT Mutated. ... Ataxia Telangiectasia Mutated Proteins - Preferred Concept UI. M0248389. Scope note. A group of PROTEIN SERINE-THREONINE ... proteínas mutadas de ataxia telangiectasia. Entry term(s). proteína A-T proteína AT mutante proteína ATM proteínas mutantes de ...

https://decs.bvsalud.org/en/ths/resource/?id=55299

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 ... The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by ... DNA-dependent protein kinase (DNA-PK), which is concerned in DNA double-strand break restore and V(D)J recombination, is ...

https://taleffectors.com/

Ataxia Telangiectasia Mutated Proteins. Prostatic Neoplasms, Castration-Resistant. Poly(ADP-ribose) Polymerase Inhibitors ... Coordination of the cellular response to DNA damage is organised by multi-domain scaffold proteins, including 53BP1 and ...

https://repository.icr.ac.uk/handle/internal/377

... and Ataxia Telangiectasia mutated (ATM) network of proteins. Loss of MRN prevents CtIP recruitment to DSBs, and partially ... and Ataxia Telangiectasia mutated (ATM) network of proteins. Loss of MRN prevents CtIP recruitment to DSBs, and partially ... and Ataxia Telangiectasia mutated (ATM) network of proteins. Loss of MRN prevents CtIP recruitment to DSBs, and partially ... N2 - Ataxia Telangiectasia mutated and RAD3-related (ATR) kinase is activated by DNA replication stress and also by various ...

https://www.research.lancs.ac.uk/portal/en/publications/mrndependent-and-independent-pathways-for-recruitment-of-topbp1-to-dna-doublestrand-breaks

Phosphorylation of H2AX acts as the foundation for recruitment of other DDR mediator proteins eventually leading to DNA repair ( Ciccia and Elledge, 2010 ). (elifesciences.org)
These types of mutations have been forecast in order to connect with ATP joining webpages theme, N-myristolylation, casein kinase II (CK2), necessary protein kinase A beneficial (PKA) phosphorylation website and you can Forkhead-related (FHA) useful internet. (phutungxemaybienhoa.com)
In this study, we evaluated retrospectively 53 patients with larynx cancer to determine whether gH2AX phosphorylation (pH2AX) alone or in combination with the membrane protein MAP17 (PDZK1IP1) could be used as prognostic biomarkers. (oncotarget.com)
As a result, it was confirmed that KU-60019, an inhibitor of ATM protein, which is a phosphorylation enzyme, recovers the functions of aging cells through activation of lysosomal functions and induction of cell proliferation. (neurosciencenews.com)
Also, in response to IONIZING RADIATION it can undergo PHOSPHORYLATION by ataxia telangiectasia mutated protein. (uchicago.edu)

The protein kinases ATM and ATR, as well as their budding yeast orthologs Tel1 and Mec1, act as master regulators of the DDR. (nih.gov)
Ataxia telangiectasia mutated (ATM), ATM- and Rad3-related protein (ATR) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are three drivers of DDR which belong to the family of phosphoinositide 3-kinase like kinases (PIKKs). (elifesciences.org)
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. (bvsalud.org)
The DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) Are stimulated by bulky adduct-containing DNA. (taleffectors.com)
Using the nucleotide-binding sites of proteins TNR kinases specifically at heart as drug-targets, several chemical libraries have already been curated that consist of substances either knownor forecasted and purified to homogeneity [8]. (immune-source.com)
In fission yeast and mammals, DNA damage activates the signalling kinases ataxia telangiectasia mutated (ATM) and Rad3-related (ATR) that simultaneously turn on DNA repair complexes and arrest cell division, allowing cells to repair damaged DNA before proceeding into mitosis. (ugent.be)
A kinase/protein array was performed to analyze if Kav001 affects any kinases/protein in response to LPS. (lupinepublishers.com)

The ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps control the rate at which cells grow and divide. (medlineplus.gov)
Researchers have identified several hundred variants (also called mutations) in the ATM gene that cause ataxia-telangiectasia. (medlineplus.gov)
Hall J. The Ataxia-telangiectasia mutated gene and breast cancer: gene expression profiles and sequence variants. (medlineplus.gov)
A gene may mutate because of aging or through mutagens such as radiation. (newhopemedicalcenter.com)
If one inherits a mutated gene, the gene can lose its supposed function. (newhopemedicalcenter.com)
When someone inherits a single mutated BRCA gene, they are at a greater risk of breast cancer. (newhopemedicalcenter.com)
However, if the other gene mutates throughout their lifetime, the cells containing the two mutated BRCA genes become cancer cells. (newhopemedicalcenter.com)
This gene is responsible for creating a protein named tumor protein p53, hence the name TP53. (newhopemedicalcenter.com)
These defects can be complemented by the reintroduction of wild type copy of Nbs1 gene, but not by a deletion mutant encoding for a protein unable to form a complex with Mre11 and Rad50 in the nucleus. (bl.uk)
Ataxia-telangiectasia (AT) is an autosomal recessive neurodegenerative disorder caused by variants of ATM (ataxia telangiectasia mutated) gene. (researchsquare.com)
AT is caused by variants of ATM (ataxia telangiectasia mutated) gene encoded on chromosome 11q22-23, which causes failure of the ATM protein, a serine/threonine kinase that participates in cellular processes for maintaining genomic stability such as identification of errors, DNA repair and cell-cycle control [3]. (researchsquare.com)
Mutation at intronic repeats of the ataxia-telangiectasia mutated (ATM) gene and ATM protein loss in primary gastric cancer with microsatellite instability. (cdc.gov)
Ataxia telangiectasia (AT), caused by mutations in the gene encoding ataxia telangiectasia mutated kinase (ATM), is a rare autosomal recessive disorder. (etsu.edu)
The ATM (ataxia telangiectasia mutated) gene product has been implicated in mitogenic signal transduction, chromosome condensation, meiotic recombination, and cell cycle control. (houstonmethodist.org)
Recently, we have shown that the ATM gene product, which is defective in the cancer-prone disorder ataxia telangiectasia (AT), influences chromosome end associations and telomere length. (houstonmethodist.org)
Retrospective studies have shown that persons heterozygous for the ataxia-telangiectasia gene, who make up about 1% of the general population, also have an excess risk of cancer, particularly breast cancer in women. (medscape.com)

Intact sensation and a negative Romberg sign are helpful in differentiating the cerebellar ataxia of ataxia-telangiectasia from Friedreich ataxia, in which the ataxia is predominantly spinal or sensory and the Romberg sign is positive. (medscape.com)
AT is characterized by complex phenotypes comprising progressive cerebellar ataxia, ocular and cutaneous telangiectasia, oculomotor apraxia, immunodeficiency at varying degrees, increased predisposition for cancers, cellular radiosensitivity and malnutrition with loss of lean body mass [3-6]. (researchsquare.com)
Most typical symptoms of AT include early onset cerebellar ataxia and dilated capillaries at the angles of the eyes and on the skin (telangiectasia). (researchsquare.com)
Ataxia Telangiectasia was described in 1926 and is characterized by telangiectasia, cerebellar Ataxia, neurological abnormalities, immunological deficiency, hypersensitivity to ionizing radiation (IR), and predisposition to cancer [ 19 ]. (biomedcentral.com)
Ataxia-telangiectasia (AT) is an autosomal recessive genetic disease characterized by progressive cerebellar ataxia, oculocutaneous telangiectasia, and recurrent respiratory and sinus infections. (medscape.com)
The first case described in the literature was a 9-year-old child with progressive cerebellar ataxia and bilateral oculocutaneous telangiectasia reported in 1941 by Madame Louis-Bar. (medscape.com)
Progressive cerebellar ataxia usually becomes clinically apparent when the child begins to walk. (medscape.com)
a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection. (medscape.com)

The main abnormalities on physical examination are ocular and cutaneous telangiectasia (see images below) and neurologic symptoms (mainly ataxia and abnormal eye movements present in virtually all cases) and choreoathetosis (30-90% of patients). (medscape.com)

Instead of activating DNA repair, the altered ATM protein allows variants to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (medlineplus.gov)
The way this likelihood works is through inheritance of mutated genes. (newhopemedicalcenter.com)
In most cases, tumor suppressor genes are the ones that mutate. (newhopemedicalcenter.com)
And when the genes in the cells of different areas of our body mutate, they can also cause cancer in those areas. (newhopemedicalcenter.com)
In a retrospective study (Abstract 154), Dr. Catherine Marshall, MD, MPH, and colleagues from Johns Hopkins University School of Medicine investigated the specificity of the PARP inhibitor, Lynparza (olaparib), toward metastatic castration-resistant prostate cancer (mCRPC) patients with mutations in either the breast cancer genes 1 and 2 (BRCA1/2) or ataxia telangiectasia mutated (ATM) genes. (pharmaceutical-technology.com)
Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. (jcircadianrhythms.com)
SWEET genes encode sugar transporter proteins and usually perform as susceptibility (S) genes. (taleffectors.com)
Using genome-wide mapping of SL interactions for DDR genes, we unraveled a dependency between the aldehyde dehydrogenase ALDH2 and the BRCA-interacting protein BRIP1. (bvsalud.org)

Ataxia-telangiectasia (AT) is a rare autosomal recessive neurodegenerative disorder that usually starts in early childhood [1,2]. (researchsquare.com)
Initially known as the Louis-Bar syndrome, the term ataxia-telangiectasia was introduced in 1958 by Boder et al, who recorded the clinical features and recognized the familial incidence proposing an autosomal recessive mode of inheritance for the disease. (medscape.com)
Ataxia-telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age-matched subjects. (medscape.com)

abstract = "Ataxia Telangiectasia mutated and RAD3-related (ATR) kinase is activated by DNA replication stress and also by various forms of DNA damage, including DNA double-strand breaks (DSBs). (lancs.ac.uk)

Serine protease, D- or L-serine arginine rich enzyme of serine threonine kinase with serine that is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC is an ɑ-amino acid that is used in the biosynthesis of proteins. (at-gen.com)
In HeLa cells, RhoA activation by HdCDT treatment increases HeLa cell survival, and this effect depends on the activity of the ataxia telangiectasia mutated (ATM) serine/threonine protein kinase [ 2 ], a DNA damage repair protein activated as a response to DNA double-strand breaks (such as those induced by ionizing radiation) [ 6 ]. (hindawi.com)
Ataxia telangiectasia mutated (ATM) is a serine-threonine protein kinase and important regulator of the DNA damage r. (cn1699.cn)
Ataxia telangiectasia mutated (ATM) is an ATP-dependent phosphatidylinositol 3-kinase-related kinase (PIKK) serine/threonine protein kinase. (cancer-research-network.com)

Close-up view of advanced telangiectasia of the bulbar conjunctiva. (medscape.com)
Telangiectasia of the bulbar conjunctiva first appears at age 3-7 years and, subsequently, involves the malar areas, palate, ears, and antecubital and popliteal spaces. (medscape.com)

The ataxia-telangiectasia mutated (ATM) protein, a DNA damage signaling regulator, facilitates DNA repair to prevent chromosome abnormalities. (elsevier.com)
About 2% of FA cases are X-linked recessive, which means that if the mother carries one mutated Fanconi anemia allele on one X chromosome , a 50% chance exists that male offspring will present with Fanconi anemia. (wikipedia.org)

Most of these variants disrupt protein production, resulting in an abnormally small, nonfunctional version of the ATM protein. (medlineplus.gov)

Fanconi Anemia Complementation Group D2 Protein" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uchicago.edu)
A Fanconi anemia complementation group protein that undergoes mono-ubiquitination by FANCL PROTEIN in response to DNA DAMAGE. (uchicago.edu)
This graph shows the total number of publications written about "Fanconi Anemia Complementation Group D2 Protein" by people in this website by year, and whether "Fanconi Anemia Complementation Group D2 Protein" was a major or minor topic of these publications. (uchicago.edu)
Below are the most recent publications written about "Fanconi Anemia Complementation Group D2 Protein" by people in Profiles. (uchicago.edu)
The ATC (ataxia-telangiectasia complementation group C) locus localizes to 11q22-q23. (medscape.com)

Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (medlineplus.gov)
Genetic polymorphisms of ataxia telangiectasia mutated affect lung cancer risk. (medlineplus.gov)
Severe reaction to radiotherapy for breast cancer as the presenting feature of ataxia telangiectasia. (medscape.com)
Xing J, Wu X, Vaporciyan AA, Spitz MR, Gu J. Prognostic significance of ataxia-telangiectasia mutated, DNA-dependent protein kinase catalytic subunit, and Ku heterodimeric regulatory complex 86-kD subunit expression in patients with nonsmall cell lung cancer. (medscape.com)

Cells without any functional ATM protein are hypersensitive to radiation and do not respond normally to DNA damage. (medlineplus.gov)
Replication Protein A (RPA), the major single stranded DNA binding protein in eukaryotes, is composed of three subunits and is a fundamental player in DNA metabolism, participating in replication, transcription, repair, and the DNA damage response. (plos.org)
In human cells in presence of DNA damage Chk2 kinase protein is activated by ATM, the protein mutated in ataxia telangiectasia (AT), and targets several substrates involved in the global DNA damage response. (bl.uk)
Unlike proteins and RNA , DNA usually lacks tertiary structure and therefore damage or disturbance does not occur at that level. (wikipedia.org)
DNA is, however, supercoiled and wound around "packaging" proteins called histones (in eukaryotes), and both superstructures are vulnerable to the effects of DNA damage. (wikipedia.org)
Unlike the DNA repair proteins, BRCA1 and BRCA2, ATM's role is as a DNA damage sensor. (pharmaceutical-technology.com)
Recruitment to sites of damage is insufficient for ATR activation as one of two known ATR activators, either topoisomerase II-binding protein (TOPBP1) or Ewing{\textquoteright}s tumor-associated antigen 1, must also be present for signaling to initiate. (lancs.ac.uk)
The ssDNA-binding protein SSB1 has been described in human cells as essential for the recognition and repair of DNA damage. (imperial.ac.uk)
Correction of ATM mutations in iPS cells from two ataxia-telangiectasia patients restores DNA damage and oxidative stress responses. (medscape.com)
Zhan H, Suzuki T, Aizawa K, Miyagawa K, Nagai R. Ataxia telangiectasia mutated (ATM)-mediated DNA damage response in oxidative stress-induced vascular endothelial cell senescence. (medscape.com)

Different clinical and immunological presentation of ataxia-telangiectasia within the same family. (medscape.com)

Biton S, Barzilai A, Shiloh Y. The neurological phenotype of ataxia-telangiectasia: solving a persistent puzzle. (medscape.com)

Nearly 50 % of the disease-associated mutations derive from nonsynonymous SNPs (nsSNPs), just one ft transform one changes the fresh amino acidic series off brand new encoded healthy protein (Cargill mais aussi al. (phutungxemaybienhoa.com)
Mutations at Walker A location and you will led to the brand new decrement away from protein stability while the forecast because of the We-Mutant and you can MuPro. (phutungxemaybienhoa.com)
Ataxia telangiectasia is a rare neurodegenerative disease caused by biallelic mutations in the ataxia telangiectasia mutat. (cn1699.cn)

Patients with ataxia-telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation. (medscape.com)

Modified FANCD2 interacts with BRCA2 PROTEIN in a stable complex with CHROMATIN, and it is involved in DNA REPAIR by homologous RECOMBINATION. (uchicago.edu)

Even in classic ataxia-telangiectasia with ataxia and telangiectasia, the onset of clinical symptoms and the rate of progression are variable. (medscape.com)
Ataxia has its onset in infancy, becoming apparent when the child begins to walk (usually from 12-14 mo). (medscape.com)
In a study of 70 patients with ataxia-telangiectasia, the incidence of the onset of symptoms of ataxia was 20% prior to age 1 year, 65% before age 2 years, and 85% by age 4 years. (medscape.com)

FA is the result of a genetic defect in a cluster of proteins responsible for DNA repair via homologous recombination . (wikipedia.org)

The ataxia telangiectasia mutated (ATM) kinase and H2AX histone tumor suppressor proteins are each critical for maintenance of cellular genomic stability and suppression of lymphomas harboring clonal translocations. (uab.edu)

however, the normal development of motor skills between ages 2-5 years tends to mask the progression of ataxia, so that parents may report an actual improvement in gait. (medscape.com)
Beyond age 5 years, the progression of the ataxia becomes increasingly apparent, and misdiagnosis of Friedreich ataxia may be made, particularly if the telangiectasia has not yet appeared. (medscape.com)
The relevant correlation between severity of ataxia and disease progression with metabolic changes such as liver function impairment and insulin resistance reinforce the importance to monitoring metabolic changes and evaluate nutritional status in these patients. (researchsquare.com)
The human ATM protein shows similarity to several yeast and mammalian proteins involved in meiotic recombination and cell cycle progression. (houstonmethodist.org)

The true incidence of ataxia-telangiectasia is unknown. (medscape.com)

Response to polysaccharide antigens in patients with ataxia-telangiectasia. (medscape.com)

This disorder is characterized by progressive difficulty with coordinating movements (ataxia) beginning in early childhood. (medlineplus.gov)
Ataxia is relentlessly progressive, but the pace is variable, even in the same sibship. (medscape.com)
Sedgwick RP, Boder E. Progressive ataxia in childhood with particular reference to ataxia-telangiectasia. (medscape.com)

Ataxia-telangiectasia combines central nervous system disease with an oculocutaneous anomaly, fulfilling the criteria for classification within the phacomatoses group of diseases. (medscape.com)

The mean age of patients with ataxia-telangiectasia at the time of presentation is 2.5-7 years. (medscape.com)

The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. (medlineplus.gov)
While by name, the protein p53 is a tumor suppressor, it also has a function in cell cycle regulation, DNA repair, programmed cell death or apoptosis, and metabolism. (newhopemedicalcenter.com)
Replication Protein A (RPA) is a single stranded DNA binding protein involved in many functions of DNA metabolism, such as DNA replication and repair. (plos.org)
Ataxia telangiectasia mutated (ATM) is a protein kinase enzyme with a crucial role in the DNA repair system, especially in DNA double-strand repair. (biomedcentral.com)

Transcription activator-like effectors (TALEs) are proteins discovered within the genus Xanthomonas of phytopathogenic micro organism. (taleffectors.com)

In general, ataxia is the first major clinical sign, and usually starts around 5-year-old [8,9]. (researchsquare.com)
Ataxia-telangiectasia: A review of movement disorders, clinical features, and genotype correlations. (medscape.com)

VCP/p97 regulates numerous cellular functions by mediating protein degradation through its segregase activity. (imperial.ac.uk)

The cause of death in more than 50% of patients with ataxia-telangiectasia is recurrent respiratory infections. (medscape.com)
More than 50% of patients with ataxia-telangiectasia die of recurrent respiratory infections, and many of the remainder develop malignancies, such as leukemia or lymphomas. (medscape.com)

The degradation of lysosomes, which are intracellular organelles responsible for autophagy and decomposition of biopolymers such as proteins and lipids in the cell, leads to cell senescence by accumulating biomolecules that must be removed in cells and causes instability of the metabolism such as removal of dysfunctional mitochondria that do not function. (neurosciencenews.com)

These proteins play a role in a wide range of signaling mechanisms in cell cycle control. (bvsalud.org)

We previously retrospectively showed that unrepaired DNA double strand breaks (DSB) as well a delay in the nucleoshuttling of the pATM protein were common features to patients with RT toxicity. (biomedcentral.com)
Patients with atypical forms of ataxia-telangiectasia are uncommon. (medscape.com)
Myoclonic jerks of the trunk and the extremities, particularly on intention, occur in some patients with ataxia-telangiectasia but not before age 9 or 10 years. (medscape.com)
Do elevated serum IgM levels have to be included in probable diagnosis criteria of patients with ataxia-telangiectasia? (medscape.com)

The ataxia affects station, gait, and intention. (medscape.com)

Description: This is Double-antibody Sandwich Enzyme-linked immunosorbent assay for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in tissue homogenates, cell lysates and other biological fluids. (1elisakits.com)
Description: Enzyme-linked immunosorbent assay based on the Double-antibody Sandwich method for detection of Human Tubulin Polymerization Promoting Protein (TPPP) in samples from tissue homogenates, cell lysates and other biological fluids with no significant corss-reactivity with analogues from other species. (1elisakits.com)

Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. (medlineplus.gov)
This loss of brain cells causes the movement problems characteristic of ataxia-telangiectasia. (medlineplus.gov)
and TAO and p38 activation is compromised in cells from a patient with ataxia telangiectasia that lack ATM. (drugbank.com)
Normal lymphoblastoid cells were exposed to different DNA damaging agents and proteins modifications and activation were evaluated. (bl.uk)

ATM deficiency decreased expression of p16 (marker of cell senescence) and activation of proapoptotic protein, GSK-3β. (etsu.edu)

ATM gene: MedlinePlus Genetics (medlineplus.gov)

Activation of Tel1ATM kinase requires Rad50 ATPase and long nucleosome-free DNA but no DNA ends - Journal of Biological... (jbc.org)

Genetics of Breast Cancer: Risk Genes According to Recent Studies - New Hope Unlimited (newhopemedicalcenter.com)

Cancers | Free Full-Text | Comprehensive Genomic Profiling Reveals Diverse but Actionable Molecular Portfolios across... (mdpi.com)

Hypertensive Women With Physically Demanding Jobs at Higher Risk of Heart Disease (medindia.net)

Frontiers | Tumor Hypoxia Drives Genomic Instability (frontiersin.org)

Hormone und Haarwachstum | Request PDF (researchgate.net)

Modulation of RhoA GTPase Activity Sensitizes Human Cervix Carcinoma Cells to γ-Radiation by Attenuating DNA Repair Pathways (hindawi.com)

TAO kinases mediate activation of p38 in response to DNA damage. | DrugBank Online (go.drugbank.com)

Jorg Goronzy's Profile | Stanford Profiles (profiles.stanford.edu)

Anatomy14

Organisms3

Diseases28

Chemicals and Drugs48

Analytical, Diagnostic and Therapeutic Techniques and Equipment9

Phenomena and Processes51

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

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

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

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

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

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

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

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

Ataxia Telangiectasia

Ataxia Telangiectasia Mutated Proteins

Telangiectasis

Telangiectasia, Hereditary Hemorrhagic

Ataxia

Tumor Suppressor Proteins

Cerebellar Ataxia

Cell Cycle Proteins

Protein-Serine-Threonine Kinases

Retinal Telangiectasis

Friedreich Ataxia

DNA-Binding Proteins

DNA Damage

Spinocerebellar Ataxias

Radiation, Ionizing

Checkpoint Kinase 2

DNA Repair

Gait Ataxia

Gamma Rays

Radiation Tolerance

Tumor Suppressor Protein p53

DNA Breaks, Double-Stranded

DNA-Activated Protein Kinase

Epistaxis

Phosphorylation

Pyrones

Activin Receptors, Type II

Arteriovenous Malformations

Histones

Nuclear Proteins

Fibroblasts

Mutation

Dose-Response Relationship, Radiation

Cell Cycle

Nijmegen Breakage Syndrome

Streptonigrin

CREST Syndrome

Cell Line

Protein Kinases

Signal Transduction

G2 Phase

DNA Replication

Chromosome Breakage

Microcephaly

Ultraviolet Rays

Heterozygote

X-Rays

Chromosome Aberrations

Apoptosis

Infrared Rays

Genes, cdc

Nucleic Acid Synthesis Inhibitors

Replication Protein A

Cell Line, Tumor

S Phase

Cell Line, Transformed

DNA Repair Enzymes

Genomic Instability

Cell Survival

Cells, Cultured

Lymphocytes

G2 Phase Cell Cycle Checkpoints

Telomere

Aphidicolin

Telomeric Repeat Binding Protein 2

Mice, Knockout

Iron-Binding Proteins

Cell Cycle Checkpoints

DNA

Phenotype

Cardiac Output, High

Hydroxyurea

Activin Receptors, Type I

Morpholines

Mutation, Missense

Comet Assay

HeLa Cells

Chromosome Disorders

Homozygote

Bleomycin