An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
Lack of stability of a joint or joint prosthesis. Factors involved are intra-articular disease and integrity of extra-articular structures such as joint capsule, ligaments, and muscles.
The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. It is a form of genome instability associated with defects in DNA MISMATCH REPAIR.
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.
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.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
A variety of simple repeat sequences that are distributed throughout the GENOME. They are characterized by a short repeat unit of 2-8 basepairs that is repeated up to 100 times. They are also known as short tandem repeats (STRs).
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
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 chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1).
A method for comparing two sets of chromosomal DNA by analyzing differences in the copy number and location of specific sequences. It is used to look for large sequence changes such as deletions, duplications, amplifications, or translocations.
An autosomal recessive disorder that causes premature aging in adults, characterized by sclerodermal skin changes, cataracts, subcutaneous calcification, muscular atrophy, a tendency to diabetes mellitus, aged appearance of the face, baldness, and a high incidence of neoplastic disease.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
An autosomal recessive disorder characterized by telangiectatic ERYTHEMA of the face, photosensitivity, DWARFISM and other abnormalities, and a predisposition toward developing cancer. The Bloom syndrome gene (BLM) encodes a RecQ-like DNA helicase.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
The cell center, consisting of a pair of CENTRIOLES surrounded by a cloud of amorphous material called the pericentriolar region. During interphase, the centrosome nucleates microtubule outgrowth. The centrosome duplicates and, during mitosis, separates to form the two poles of the mitotic spindle (MITOTIC SPINDLE APPARATUS).
DNA present in neoplastic tissue.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
The process by which a DNA molecule is duplicated.
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.
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.
The loss of one allele at a specific locus, caused by a deletion mutation; or loss of a chromosome from a chromosome pair, resulting in abnormal HEMIZYGOSITY. It is detected when heterozygous markers for a locus appear monomorphic because one of the ALLELES was deleted.
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.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
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.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
Defective nuclei produced during the TELOPHASE of MITOSIS or MEIOSIS by lagging CHROMOSOMES or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes.
The genetic complement of an organism, including all of its GENES, as represented in its DNA, or in some cases, its RNA.
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 chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.
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.
The systematic study of the complete DNA sequences (GENOME) of organisms.
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.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
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.
The number of copies of a given gene present in the cell of an organism. An increase in gene dosage (by GENE DUPLICATION for example) can result in higher levels of gene product formation. GENE DOSAGE COMPENSATION mechanisms result in adjustments to the level GENE EXPRESSION when there are changes or differences in gene dosage.
Proteins that catalyze the unwinding of duplex DNA during replication by binding cooperatively to single-stranded regions of DNA or to short regions of duplex DNA that are undergoing transient opening. In addition DNA helicases are DNA-dependent ATPases that harness the free energy of ATP hydrolysis to translocate DNA strands.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A selective increase in the number of copies of a gene coding for a specific protein without a proportional increase in other genes. It occurs naturally via the excision of a copy of the repeating sequence from the chromosome and its extrachromosomal replication in a plasmid, or via the production of an RNA transcript of the entire repeating sequence of ribosomal RNA followed by the reverse transcription of the molecule to produce an additional copy of the original DNA sequence. Laboratory techniques have been introduced for inducing disproportional replication by unequal crossing over, uptake of DNA from lysed cells, or generation of extrachromosomal sequences from rolling circle replication.
A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.
New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.
An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.
A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.
Mapping of the KARYOTYPE of a cell.
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.
Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.
The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development.
A form of GENE LIBRARY containing the complete DNA sequences present in the genome of a given organism. It contrasts with a cDNA library which contains only sequences utilized in protein coding (lacking introns).
The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).
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.
Highly repetitive DNA sequences found in HETEROCHROMATIN, mainly near centromeres. They are composed of simple sequences (very short) (see MINISATELLITE REPEATS) repeated in tandem many times to form large blocks of sequence. Additionally, following the accumulation of mutations, these blocks of repeats have been repeated in tandem themselves. The degree of repetition is on the order of 1000 to 10 million at each locus. Loci are few, usually one or two per chromosome. They were called satellites since in density gradients, they often sediment as distinct, satellite bands separate from the bulk of genomic DNA owing to a distinct BASE COMPOSITION.
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
MutS homolog 2 protein is found throughout eukaryotes and is a homolog of the MUTS DNA MISMATCH-BINDING PROTEIN. It plays an essential role in meiotic RECOMBINATION and DNA REPAIR of mismatched NUCLEOTIDES.
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.
Chromic acid (H2Cr2O7), dipotassium salt. A compound having bright orange-red crystals and used in dyeing, staining, tanning leather, as bleach, oxidizer, depolarizer for dry cells, etc. Medically it has been used externally as an astringent, antiseptic, and caustic. When taken internally, it is a corrosive poison.
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.
Tumors or cancer of the COLON or the RECTUM or both. Risk factors for colorectal cancer include chronic ULCERATIVE COLITIS; FAMILIAL POLYPOSIS COLI; exposure to ASBESTOS; and irradiation of the CERVIX UTERI.
Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.
An exchange of DNA between matching or similar sequences.
Established cell cultures that have the potential to propagate indefinitely.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
Any method used for determining the location of and relative distances between genes on a chromosome.
Stretches of genomic DNA that exist in different multiples between individuals. Many copy number variations have been associated with susceptibility or resistance to disease.
Interruptions in the sugar-phosphate backbone of DNA.
A situation where one member (allele) of a gene pair is lost (LOSS OF HETEROZYGOSITY) or amplified.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
A type of chromosome aberration characterized by CHROMOSOME BREAKAGE and transfer of the broken-off portion to another location, often to a different chromosome.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Distinct units in some bacterial, bacteriophage or plasmid GENOMES that are types of MOBILE GENETIC ELEMENTS. Encoded in them are a variety of fitness conferring genes, such as VIRULENCE FACTORS (in "pathogenicity islands or islets"), ANTIBIOTIC RESISTANCE genes, or genes required for SYMBIOSIS (in "symbiosis islands or islets"). They range in size from 10 - 500 kilobases, and their GC CONTENT and CODON usage differ from the rest of the genome. They typically contain an INTEGRASE gene, although in some cases this gene has been deleted resulting in "anchored genomic islands".
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
A cell line derived from cultured tumor cells.
Congenital disorder affecting all bone marrow elements, resulting in ANEMIA; LEUKOPENIA; and THROMBOPENIA, and associated with cardiac, renal, and limb malformations as well as dermal pigmentary changes. Spontaneous CHROMOSOME BREAKAGE is a feature of this disease along with predisposition to LEUKEMIA. There are at least 7 complementation groups in Fanconi anemia: FANCA, FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL. (from Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=227650, August 20, 2004)
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.
A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
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.
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.
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.
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.
Induction and quantitative measurement of chromosomal damage leading to the formation of micronuclei (MICRONUCLEI, CHROMOSOME-DEFECTIVE) in cells which have been exposed to genotoxic agents or IONIZING RADIATION.
Polonium. A radioactive element that is a member of the chalcogen family. It has the atomic symbol Po, atomic number 84, and the atomic weight of the isotope with the longest half-life (209Po) is 208.98. It decays by alpha-emission.
Highly repeated sequences, 6K-8K base pairs in length, which contain RNA polymerase II promoters. They also have an open reading frame that is related to the reverse transcriptase of retroviruses but they do not contain LTRs (long terminal repeats). Copies of the LINE 1 (L1) family form about 15% of the human genome. The jockey elements of Drosophila are LINEs.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
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.
Specific loci that show up during KARYOTYPING as a gap (an uncondensed stretch in closer views) on a CHROMATID arm after culturing cells under specific conditions. These sites are associated with an increase in CHROMOSOME FRAGILITY. They are classified as common or rare, and by the specific culture conditions under which they develop. Fragile site loci are named by the letters "FRA" followed by a designation for the specific chromosome, and a letter which refers to which fragile site of that chromosome (e.g. FRAXA refers to fragile site A on the X chromosome. It is a rare, folic acid-sensitive fragile site associated with FRAGILE X SYNDROME.)
Damages to reproductive health prior to conception (FERTILIZATION), a legal term for torts liability concerning environmental safety issues. Preconception injuries may involve either the male or the female, such as chromosomal mutations in the OVA or the SPERMATOZOA.
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Susceptibility of chromosomes to breakage leading to translocation; CHROMOSOME INVERSION; SEQUENCE DELETION; or other CHROMOSOME BREAKAGE related aberrations.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)
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.
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)
Actual loss of portion of a chromosome.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
The result of a positive or negative response (to drugs, for example) in one cell being passed onto other cells via the GAP JUNCTIONS or the intracellular milieu.
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.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The relationships of groups of organisms as reflected by their genetic makeup.
Changes in the organism associated with senescence, occurring at an accelerated rate.
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. Aurora A overexpression in many malignant tumor types suggests that it may be directly involved in NEOPLASTIC CELL TRANSFORMATION.
The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
The simultaneous identification of all chromosomes from a cell by fluorescence in situ hybridization (IN SITU HYBRIDIZATION, FLUORESCENCE) with chromosome-specific florescent probes that are discerned by their different emission spectra.
Genotypic differences observed among individuals in a population.
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.
Biochemical identification of mutational changes in a nucleotide sequence.
Tumors or cancer of the human BREAST.
An individual having different alleles at one or more loci regarding a specific character.
The complete gene complement contained in a set of chromosomes in a fungus.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
A technique for visualizing CHROMOSOME ABERRATIONS using fluorescently labeled DNA probes which are hybridized to chromosomal DNA. Multiple fluorochromes may be attached to the probes. Upon hybridization, this produces a multicolored, or painted, effect with a unique color at each site of hybridization. This technique may also be used to identify cross-species homology by labeling probes from one species for hybridization with chromosomes from another species.
The repair of DOUBLE-STRAND DNA BREAKS by rejoining the broken ends of DNA to each other directly.
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.
A group of autosomal-dominant inherited diseases in which COLON CANCER arises in discrete adenomas. Unlike FAMILIAL POLYPOSIS COLI with hundreds of polyps, hereditary nonpolyposis colorectal neoplasms occur much later, in the fourth and fifth decades. HNPCC has been associated with germline mutations in mismatch repair (MMR) genes. It has been subdivided into Lynch syndrome I or site-specific colonic cancer, and LYNCH SYNDROME II which includes extracolonic cancer.
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).
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
DNA constructs that are composed of, at least, a REPLICATION ORIGIN, for successful replication, propagation to and maintenance as an extra chromosome in bacteria. In addition, they can carry large amounts (about 200 kilobases) of other sequence for a variety of bioengineering purposes.
The variable phenotypic expression of a GENE depending on whether it is of paternal or maternal origin, which is a function of the DNA METHYLATION pattern. Imprinted regions are observed to be more methylated and less transcriptionally active. (Segen, Dictionary of Modern Medicine, 1992)
A phenotypically recognizable genetic trait which can be used to identify a genetic locus, a linkage group, or a recombination event.
A copy number variation that results in reduced GENE DOSAGE due to any loss-of-function mutation. The loss of heterozygosity is associated with abnormal phenotypes or diseased states because the remaining gene is insufficient.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
Family of retrovirus-associated DNA sequences (ras) originally isolated from Harvey (H-ras, Ha-ras, rasH) and Kirsten (K-ras, Ki-ras, rasK) murine sarcoma viruses. Ras genes are widely conserved among animal species and sequences corresponding to both H-ras and K-ras genes have been detected in human, avian, murine, and non-vertebrate genomes. The closely related N-ras gene has been detected in human neuroblastoma and sarcoma cell lines. All genes of the family have a similar exon-intron structure and each encodes a p21 protein.
The degree of replication of the chromosome set in the karyotype.
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.
The number of mutations that occur in a specific sequence, GENE, or GENOME over a specified period of time such as years, CELL DIVISIONS, or generations.
A specific pair of GROUP C CHROMOSOMES of the human chromosome classification.
Deletion of sequences of nucleic acids from the genetic material of an individual.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
Low-copy (2-50) repetitive DNA elements that are highly homologous and range in size from 1000 to 400,000 base pairs.
A microtubule structure that forms during CELL DIVISION. It consists of two SPINDLE POLES, and sets of MICROTUBULES that may include the astral microtubules, the polar microtubules, and the kinetochore microtubules.
Family of retrovirus-associated DNA sequences (myc) originally isolated from an avian myelocytomatosis virus. The proto-oncogene myc (c-myc) codes for a nuclear protein which is involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Truncation of the first exon, which appears to regulate c-myc expression, is crucial for tumorigenicity. The human c-myc gene is located at 8q24 on the long arm of chromosome 8.
The genetic complement of a BACTERIA as represented in its DNA.
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)
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
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.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
A specific pair of GROUP E CHROMOSOMES of the human chromosome classification.
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.
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.
A large, nuclear protein, encoded by the BRCA2 gene (GENE, BRCA2). Mutations in this gene predispose humans to breast and ovarian cancer. The BRCA2 protein is an essential component of DNA repair pathways, suppressing the formation of gross chromosomal rearrangements. (from Genes Dev. 2000;14(11):1400-6)
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A type of mutation in which a number of NUCLEOTIDES deleted from or inserted into a protein coding sequence is not divisible by three, thereby causing an alteration in the READING FRAMES of the entire coding sequence downstream of the mutation. These mutations may be induced by certain types of MUTAGENS or may occur spontaneously.
A diverse group of proteins whose genetic MUTATIONS have been associated with the chromosomal instability syndrome FANCONI ANEMIA. Many of these proteins play important roles in protecting CELLS against OXIDATIVE STRESS.
The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING.
Complex nucleoprotein structures which contain the genomic DNA and are part of the CELL NUCLEUS of MAMMALS.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.
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).
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.
A region of DNA that is highly polymorphic and is prone to strand breaks, rearrangements or other MUTATIONS because of the nature of its sequence. These regions often harbor palindromic, or repetitive sequences (REPETITIVE SEQUENCES, NUCLEIC ACID). Variability in stability of the DNA sequence is seen at CHROMOSOME FRAGILE SITES.
Pathological processes that tend eventually to become malignant. (From Dorland, 27th ed)
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
The process by which the CYTOPLASM of a cell is divided.
An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or 6-mercaptopurine to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC 2.4.2.8.
The phase of cell nucleus division following PROMETAPHASE, in which the CHROMOSOMES line up across the equatorial plane of the SPINDLE APPARATUS prior to separation.
Examination of CHROMOSOMES to diagnose, classify, screen for, or manage genetic diseases and abnormalities. Following preparation of the sample, KARYOTYPING is performed and/or the specific chromosomes are analyzed.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
The chromosomal constitution of cells, in which each type of CHROMOSOME is represented twice. Symbol: 2N or 2X.
The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.
A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)
An autosomal recessive syndrome occurring principally in females, characterized by the presence of reticulated, atrophic, hyperpigmented, telangiectatic cutaneous plaques, often accompanied by juvenile cataracts, saddle nose, congenital bone defects, disturbances in the growth of HAIR; NAILS; and TEETH; and HYPOGONADISM.
Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.
Tumors or cancer of the COLON.
Immunologically detectable substances found in the CELL NUCLEUS.
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
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.
Discrete segments of DNA which can excise and reintegrate to another site in the genome. Most are inactive, i.e., have not been found to exist outside the integrated state. DNA transposable elements include bacterial IS (insertion sequence) elements, Tn elements, the maize controlling elements Ac and Ds, Drosophila P, gypsy, and pogo elements, the human Tigger elements and the Tc and mariner elements which are found throughout the animal kingdom.
Elements of limited time intervals, contributing to particular results or situations.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
Microsatellite repeats consisting of three nucleotides dispersed in the euchromatic arms of chromosomes.
The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.
Deoxyribonucleic acid that makes up the genetic material of fungi.
Study of the scientific principles, mechanisms, and effects of the interaction of ionizing radiation with living matter. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
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.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
A general term for various neoplastic diseases of the lymphoid tissue.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
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.
The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.

Modelling developmental instability as the joint action of noise and stability: a Bayesian approach. (1/2256)

BACKGROUND: Fluctuating asymmetry is assumed to measure individual and population level developmental stability. The latter may in turn show an association with stress, which can be observed through asymmetry-stress correlations. However, the recent literature does not support an ubiquitous relationship. Very little is known why some studies show relatively strong associations while others completely fail to find such a correlation. We propose a new Bayesian statistical framework to examine these associations RESULTS: We are considering developmental stability - i.e. the individual buffering capacity - as the biologically relevant trait and show that (i) little variation in developmental stability can explain observed variation in fluctuating asymmetry when the distribution of developmental stability is highly skewed, and (ii) that a previously developed tool (i.e. the hypothetical repeatability of fluctuating asymmetry) contains only limited information about variation in developmental stability, which stands in sharp contrast to the earlier established close association between the repeatability and developmental instability. CONCLUSION: We provide tools to generate valuable information about the distribution of between-individual variation in developmental stability. A simple linear transformation of a previous model lead to completely different conclusions. Thus, theoretical modelling of asymmetry and stability appears to be very sensitive to the scale of inference. More research is urgently needed to get better insights in the developmental mechanisms of noise and stability. In spite of the fact that the model is likely to represent an oversimplification of reality, the accumulation of new insights could be incorporated in the Bayesian statistical approach to obtain more reliable estimation.  (+info)

Comparative genomics of microbial pathogens and symbionts. (2/2256)

We are interested in quantifying the contribution of gene acquisition, loss, expansion and rearrangements to the evolution of microbial genomes. Here, we discuss factors influencing microbial genome divergence based on pair-wise genome comparisons of closely related strains and species with different lifestyles. A particular focus is on intracellular pathogens and symbionts of the genera Rickettsia, Bartonella and BUCHNERA: Extensive gene loss and restricted access to phage and plasmid pools may provide an explanation for why single host pathogens are normally less successful than multihost pathogens. We note that species-specific genes tend to be shorter than orthologous genes, suggesting that a fraction of these may represent fossil-orfs, as also supported by multiple sequence alignments among species. The results of our genome comparisons are placed in the context of phylogenomic analyses of alpha and gamma proteobacteria. We highlight artefacts caused by different rates and patterns of mutations, suggesting that atypical phylogenetic placements can not a priori be taken as evidence for horizontal gene transfer events. The flexibility in genome structure among free-living microbes contrasts with the extreme stability observed for the small genomes of aphid endosymbionts, in which no rearrangements or inflow of genetic material have occurred during the past 50 millions years (1). Taken together, the results suggest that genomic stability correlate with the content of repeated sequences and mobile genetic elements, and thereby indirectly with bacterial lifestyles.  (+info)

Increased cell proliferation is associated with genomic instability: elevated micronuclei frequencies in estradiol-treated human ovarian cancer cells. (3/2256)

Estrogen-related cancers are often associated with the hormone's tumor promoting activity. Recently, estradiol has also been demonstrated to induce gene mutations in the physiological concentration range. Mitotic disturbances are found at higher concentrations. In the present study we demonstrate data suggesting an additional mechanism for the induction of genetic damage, i.e. chromosomal breakage. Estrogen receptor-positive (BG-1) and -negative (UCI) human ovarian cancer cell lines were investigated for micronucleus formation after treatment with estradiol. BG-1 cells but not UCI cells showed an increase in micronucleus formation which correlated with the estradiol-induced cell proliferation. The specific estradiol receptor antagonist hydroxytamoxifen suppressed the formation of micronuclei in BG-1 cells. Increased micronucleus frequencies were also seen after normalization of the data to the number of cell divisions. Kinetochore analysis revealed a difference between micronuclei induced by picomolar concentrations of estradiol (kinetochore-negative) and micromolar concentrations (predominantly kinetochore-positive) leading to mitotic disturbances. In accordance with this finding, analysis of the cell cycle revealed decreased cell numbers in G(2)/M phase after treatment with picomolar concentrations, usually not found after mitotic disturbances. We hypothesize that hormone-specific forcing of responsive cells through the cell cycle leads to an override of checkpoints operating under homeostatic control of the cell cycle, resulting in genomic instability.  (+info)

Variation in the extent of microsatellite instability in human cell lines with defects in different mismatch repair genes. (4/2256)

Mismatch repair deficiency results in the elevation of mutation rates in tumors, which is especially pronounced in simple repeat sequences (microsatellites). We have investigated the relationship between microsatellite mutagenesis and certain combinations of mutations in mismatch repair genes, using a frameshift reversion assay to determine the spontaneous mutation rates of a dinucleotide microsatellite in two cancer cell lines, HCT116, which has defects in hMLH1 and hMSH3, and HEC-1-A, which has defects in hPMS2 and hMSH6. We found a 10-fold difference in mutation rates between these two cell lines. In addition, a mutant hPMS2 allele, PMS134, which has been reported to have a dominant negative effect, was expressed in mismatch repair-proficient telomerase-immortalized hTERT-1604 fibroblasts and mutation rates were determined. Expression of PMS134 did not elevate mutation rates in hTERT-1604. Combined, these results suggest that mutations in different mismatch repair genes can lead to varying degrees of microsatellite instability. It is also likely that there is heterogeneity in the mutations that are acquired in the absence of mismatch repair, such that some mismatch repair-defective cancer cells also contain mutations in other genes coding for proteins involved in the maintenance of genetic stability.  (+info)

Gain of chromosome 8q23-24 is a predictive marker for lymph node positivity in colorectal cancer. (5/2256)

PURPOSE: The prognosis of patients with colorectal cancer is largely determined by tumor stage. In this respect, colorectal cancers with lymph node metastases indicate a worse prognosis versus lymph node-negative tumors. Accordingly, there is considerable clinical interest in understanding the genetic mechanisms underlying metastasis formation. Furthermore, sensitive and specific biomarkers are needed to predict the metastatic phenotype at the time of diagnosis. EXPERIMENTAL DESIGN: Fifty colorectal cancers with or without lymph node metastases were assessed for genomic imbalances by comparative genomic hybridization. Particular interest was focused on whether specific chromosomal alterations exist in primary tumors that might be indicative and specific for the metastatic phenotype. RESULTS: The analysis revealed that lymph node-positive colorectal cancers show a higher degree of chromosomal instability than lymph node-negative cancers (average number of chromosomal copy alterations, 9.8 versus 7.5). Chromosomal alterations commonly described in colorectal cancers such as gain of 20q or loss of 18q21 were not different. However, the gain of chromosomal region 8q23-24 was seen in the vast majority of lymph node-positive cancers, whereas it was rather rare in lymph node-negative carcinomas (P = 0.0016). CONCLUSIONS: These data suggest that genes located at 8q23-24 might favor the development of lymphatic metastases in colorectal cancers. Additionally, the gain of this region could be used to predict the metastatic potential of primary colorectal cancers.  (+info)

Positive and negative roles of homologous recombination in the maintenance of genome stability in Saccharomyces cerevisiae. (6/2256)

In previous studies of the loss of heterozygosity (LOH), we analyzed a hemizygous URA3 marker on chromosome III in S. cerevisiae and showed that homologous recombination is involved in processes that lead to LOH in multiple ways, including allelic recombination, chromosome size alterations, and chromosome loss. To investigate the role of homologous recombination more precisely, we examined LOH events in rad50 Delta, rad51 Delta, rad52 Delta, rad50 Delta rad52 Delta, and rad51 Delta rad52 Delta mutants. As compared to Rad(+) cells, the frequency of LOH was significantly increased in all mutants, and most events were chromosome loss. Other LOH events were differentially affected in each mutant: the frequencies of all types of recombination were decreased in rad52 mutants and enhanced in rad50 mutants. The rad51 mutation increased the frequency of ectopic but not allelic recombination. Both the rad52 and rad51 mutations increased the frequency of intragenic point mutations approximately 25-fold, suggesting that alternative mutagenic pathways partially substitute for homologous recombination. Overall, these results indicate that all of the genes are required for chromosome maintenance and that they most likely function in homologous recombination between sister chromatids. In contrast, other recombination pathways can occur at a substantial level even in the absence of one of the genes and contribute to generating various chromosome rearrangements.  (+info)

Single-nucleotide polymorphisms of the Trypanosoma cruzi MSH2 gene support the existence of three phylogenetic lineages presenting differences in mismatch-repair efficiency. (7/2256)

We have identified single-nucleotide polymorphisms (SNPs) in the mismatch-repair gene TcMSH2 from Trypanosoma cruzi. Phylogenetic inferences based on the SNPs, confirmed by RFLP analysis of 32 strains, showed three distinct haplogroups, denominated A, B, and C. Haplogroups A and C presented strong identity with the previously described T. cruzi lineages I and II, respectively. A third haplogroup (B) was composed of strains presenting hybrid characteristics. All strains from a haplogroup encoded the same specific protein isoform, called, respectively, TcMHS2a, TcMHS2b, and TcMHS2c. The classification into haplogroups A, B, and C correlated with variation in the efficiency of mismatch repair in these cells. When microsatellite loci of strains representative of each haplogroup were analyzed after being cultured in the presence of hydrogen peroxide, new microsatellite alleles were definitely seen in haplogroups B and C, while no evidence of microsatellite instability was found in haplogroup A. Also, cells from haplogroups B and C were considerably more resistant to cisplatin treatment, a characteristic known to be conferred by deficiency of mismatch repair in eukaryotic cells. Altogether, our data suggest that strains belonging to haplogroups B and C may have decreased mismatch-repair ability when compared with strains assigned to the haplogroup A lineage.  (+info)

Ensuring the stability of the genome: DNA damage checkpoints. (8/2256)

The cellular response to DNA damage is vital for the cell"s ability to maintain genomic integrity. Checkpoint signalling pathways, which induce a cell cycle arrest in response to DNA damage, are an essential component of this process. This is reflected by the functional conservation of these pathways in all eukaryotes from yeast to mammalian cells. This review will examine the cellular response to DNA damage throughout the cell cycle. A key component of the DNA damage response is checkpoint signalling, which monitors the state of the genome prior to DNA replication (G1/S) and chromosome segregation (G2/M). Checkpoint signalling in model systems including mice, Xenopus laevis, Drosophila melanogaster, and the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe have been useful in elucidating these pathways in mammalian cells. An examination of this research, with emphasis on the function of checkpoint proteins, their relationship to DNA repair, and their involvement in oncogenesis is undertaken here.  (+info)

To cause genomic instability particularly at chromosome loci that are intrinsically difficult to replicate because of the complexity of secondary structures or
DNA replication is tightly regulated, but paradoxically there is reported to be an excess of MCM DNA replication proteins over the number of replication origins. Here, we show that MCM levels in primary human T cells are induced during the G(0)--,G(1) transition and are not in excess in proliferating cells. The level of induction is critical as we show that a 50% reduction leads to increased centromere separation, premature chromatid separation (PCS) and gross chromosomal abnormalities typical of genomic instability syndromes. We investigated the mechanisms involved and show that a reduction in MCM levels causes dose-dependent DNA damage involving activation of ATR & ATM and Chk1 & Chk2. There is increased DNA mis-repair by non-homologous end joining (NHEJ) and both NHEJ and homologous recombination are necessary for Mcm7-depleted cells to progress to metaphase. Therefore, a simple reduction in MCM loading onto DNA, which occurs in cancers as a result of aberrant cell cycle control, is ...
R‐loops, formed by co‐transcriptional DNA-RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent R‐loop accumulation centers on the conserved THO/TREX complex, an RNA‐binding factor involved in transcription elongation and RNA export that contributes to messenger ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear. To understand how THO restrains harmful R‐loops, we searched for new THO‐interacting factors. We found that human THO interacts with the Sin3A histone deacetylase complex to suppress co‐transcriptional R‐loops, DNA damage, and replication impairment. Functional analyses show that histone hypo‐acetylation prevents accumulation of harmful R‐loops and RNA‐mediated genomic instability. Diminished histone deacetylase activity in THO‐ and Sin3A‐depleted cell lines correlates with increased R‐loop formation, ...
R‐loops, formed by co‐transcriptional DNA-RNA hybrids and a displaced DNA single strand (ssDNA), fulfill certain positive regulatory roles but are also a source of genomic instability. One key cellular mechanism to prevent R‐loop accumulation centers on the conserved THO/TREX complex, an RNA‐binding factor involved in transcription elongation and RNA export that contributes to messenger ribonucleoprotein (mRNP) assembly, but whose precise function is still unclear. To understand how THO restrains harmful R‐loops, we searched for new THO‐interacting factors. We found that human THO interacts with the Sin3A histone deacetylase complex to suppress co‐transcriptional R‐loops, DNA damage, and replication impairment. Functional analyses show that histone hypo‐acetylation prevents accumulation of harmful R‐loops and RNA‐mediated genomic instability. Diminished histone deacetylase activity in THO‐ and Sin3A‐depleted cell lines correlates with increased R‐loop formation, ...
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. The phosphatidylinositol 3-kinase δ (PI3Kδ) pathway regulates AID by suppressing its expression in B cells. Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. Here we show that treatment of primary mouse B cells with idelalisib or duvelisib, and to a lesser extent ibrutinib, enhanced the expression of AID and increased ...
TY - JOUR. T1 - Myc-Dependent Genome Instability and Lifespan in Drosophila. AU - Greer, Christina. AU - Lee, Moonsook. AU - Westerhof, Maaike. AU - Milholland, Brandon. AU - Spokony, Rebecca. AU - Vijg, Jan. AU - Secombe, Julie. PY - 2013/9/6. Y1 - 2013/9/6. N2 - The Myc family of transcription factors are key regulators of cell growth and proliferation that are dysregulated in a large number of human cancers. When overexpressed, Myc family proteins also cause genomic instability, a hallmark of both transformed and aging cells. Using an in vivo lacZ mutation reporter, we show that overexpression of Myc in Drosophila increases the frequency of large genome rearrangements associated with erroneous repair of DNA double-strand breaks (DSBs). In addition, we find that overexpression of Myc shortens adult lifespan and, conversely, that Myc haploinsufficiency reduces mutation load and extends lifespan. Our data provide the first evidence that Myc may act as a pro-aging factor, possibly through its ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneuploidy. Genome instability does occur in bacteria. In multicellular organisms genome instability is central to carcinogenesis, and in humans it is also a factor in some neurodegenerative diseases such as amyotrophic lateral sclerosis or the neuromuscular disease myotonic dystrophy. The sources of genome instability have only recently begun to be elucidated. A high frequency of externally caused DNA damage can be one source of genome instability since DNA damages can cause inaccurate translesion synthesis past the damages or errors in repair, leading to mutation. Another source of genome instability may be epigenetic or mutational reductions in expression of DNA repair genes. Because endogenous (metabolically-caused) DNA damage is very frequent, ...
Large-scale genomic studies have demonstrated that approximately 50% of high-grade serous ovarian cancers (HGSOCs) harbor genetic and epigenetic alterations in homologous recombination repair (HRR) pathway genes. The most commonly altered HRR genes are BRCA1 and BRCA2, followed by other Fanconi Anemia genes. Loss of HRR causes genomic instability, hyperdependence on alternative DNA repair mechanisms, and enhanced sensitivity to PARP-inhibitors (PARPi) through the mechanism of synthetic lethality. PARP inhibitor resistance has emerged as a vexing clinical problem for the treatment of BRCA1/2 deficient tumors. The most prevalent mechanism of PARPi resistance is secondary events that cancel the original HRR alteration and restore HRR proficiency. PARPi resistance also develops without restoration of HRR proficiency through enhanced replication fork (RF) stabilization. We have recently made the surprising observation that BRCA2-deficient tumor cells can stabilize their replication forks and become ...
Tumor-suppressor recruits help to overcome a barrier and fix cancer-causing defects. Like a mechanic popping the hood of a car to get at a faulty engine, a tumor-suppressing protein allows cellular repair mechanisms to pounce on damaged DNA by overcoming a barrier to DNA access.. Reporting online at Nature Cell Biology this week, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center shows that BRIT1 connects with another protein complex to relax DNAs tight packaging at the site of the damage.. Relaxing this barrier allows two different DNA repair pathways greater access to the damage, preventing flawed DNA from being passed on as the cell divides, which causes genomic instability leading to cancer, said senior author Shiaw-Yih Lin, Ph.D., assistant professor in M. D. Andersons Department of Systems Biology.. BRIT1 is under-expressed in human ovarian, breast and prostate cancer cell lines. Lin and colleagues previously showed that the protein plays a key ...
Correct control of cell cycle development requires the functionality of a little category of activating phosphatases termed Cdc25, which were implicated in tumor and Alzheimers disease. proliferation or success. The co-expression of Cdc25A or Cdc25B cooperates with either oncogenic HRAS or the increased loss of RB1 to transform mouse embryonic fibroblasts allowing them to create tumors in mice [14]. It really is widely thought that overexpression of Cdc25A and Cdc25B allows the bypass of regular cell routine checkpoints, that leads to a lack of genome integrity [10, 15]. Certainly, deregulation of Cdc25A appearance promotes mammary tumorigenesis and causes genomic instability [16]. Additionally, Cdc25A may donate to mobile transformation and lower responsiveness to tension by ablating the activities from the redox-sensitive apoptotic signaling kinase ASK1. Cdc25A provides been proven to inhibit ASK1 activation with a non-catalytic protein-protein discussion that blocks ASK1 dimerization, which ...
DNA-protein crosslinks (DPCs) are under-investigated DNA lesions caused by the covalent attachment of proteins to DNA. DPCs are induced by various endogenous chemicals like aldehydes or by chemotherapeutic drugs. Little is known about how cells repair DPCs and thus acquire resistance to DPC-induced chemotherapy. However, the persistence of DPCs causes genomic instability and cancer. We recently discovered a human syndrome (Ruijs-Aalfs or SPARTAN syndrome) related to the defective DPC repair pathway.
Despite its benefits in cancer treatment, ionising radiation (IR) can induce a series of adverse acute and/or long term effects. Studies on A-bomb survivors and radiotherapy patients have shown that acute whole-body exposure results in an increased risk for radiation-induced Acute Myeloid Leukaemia (r-AML), a bone marrow (BM) malignancy; whereas local-radiotherapy patients run the risk of developing acute and/or long term normal tissue reactions. Irradiated BM cells manifest persistent radiation-induced genomic instability. BM is one of the most susceptible tissues to radiation-induced cancer and one of the most radiosensitive tissues, which proposes a link between cancer susceptibility, genomic instability and radiosensitivity. The exact mechanism by which exposure of BM cells to IR leads to malignant transformation is still unclear, but the non-targeted nature of radiation-induced damage and genomic instability could suggest that an epigenetic mechanism is also involved; and DNA methylation is ...
Genomic instability plays a key role in driving cancer development. It is already found in precancerous lesions and allows the acquisition of additional cancerous features. A major source of genomic instability in early stages of tumorigenesis is DNA replication stress. Normally, origin licensing and activation, as well as replication fork progression, are tightly regulated to allow faithful duplication of the genome. Aberrant origin usage and/or perturbed replication fork progression leads to DNA damage and genomic instability. Oncogene activation is an endogenous source of replication stress, disrupting replication regulation and inducing DNA damage. Oncogene-induced replication stress and its role in cancer development have been studied comprehensively, however its molecular basis is still unclear. Here, we review the current understanding of replication regulation, its potential disruption and how oncogenes perturb the replication and induce DNA damage leading to genomic instability in cancer.
Dr. Changs research program focuses on telomeres,repetitive DNA sequences at the ends of chromosomes critically important for the maintenance of genome stability. Perturbation of telomere length results in telomere dysfunction, leading to increased genomic instability that can promote early aging and cancer development. Dr. Changs laboratory was the first togenerate a faithful mouse model of Werner Syndrome (WS). This rare disease strikes individuals in their 30s and is marked by the development of aging phenotypes and early onset of cancer.. Dr. Chang found that when WRN deficiency is coupled withtelomere dysfunction, the combination increases genomic instability, pre-matureaging and increased tumorigenesis. In addition, his findings conclusively demonstrate that telomere status plays an important role in the development of premature aging pathologies observed in WS patients. With this mouse model, Dr. Changs laboratory has also identified common genetic pathways that unify aging and cancer ...
Dr. Changs research program focuses on telomeres,repetitive DNA sequences at the ends of chromosomes critically important for the maintenance of genome stability. Perturbation of telomere length results in telomere dysfunction, leading to increased genomic instability that can promote early aging and cancer development. Dr. Changs laboratory was the first togenerate a faithful mouse model of Werner Syndrome (WS). This rare disease strikes individuals in their 30s and is marked by the development of aging phenotypes and early onset of cancer.. Dr. Chang found that when WRN deficiency is coupled withtelomere dysfunction, the combination increases genomic instability, pre-matureaging and increased tumorigenesis. In addition, his findings conclusively demonstrate that telomere status plays an important role in the development of premature aging pathologies observed in WS patients. With this mouse model, Dr. Changs laboratory has also identified common genetic pathways that unify aging and cancer ...
Inverted repeats have been found to occur in both prokaryotic and eukaryotic genomes. Usually they are short and some have important functions in various biological processes. However, long inverted repeats are rare and can cause genome instability. Analyses of C. elegans genome identified long, nearly-perfect inverted repeat sequences involving both divergently and convergently oriented homologous gene pairs and complete intergenic sequences. Comparisons with the orthologous regions from the genomes of C. briggsae and C. remanei show that the inverted repeat structures are often far more conserved than the sequences. This observation implies that there is an active mechanism for maintaining the inverted repeat nature of the sequences.
Shepard JL, Amatruda JF, Stern HM, Subramanian A, Finkelstein D, Ziai J, Finley KR, Pfaff KL, Hersey C, Zhou Y, Barut B, Freedman M, Lee C, Spitsbergen J, Neuberg D, Weber G, Golub TR, Glickman JN, Kutok JL, Aster JC, Zon LI (2005) A zebrafish bmyb mutation causes genome instability and increased cancer susceptibility. Proc Natl Acad Sci USA 102: 13194-13199 ...
Hannes Alfvén. Plasma instabilities are not well-known to the general public, or among astronomers. They refer to distortions that occur when plasmas are generated and confined. They are often confused with phenomena observed in fluid interactions: Kelvin-Helmholtz instabilities, or Rayleigh-Taylor instabilities, for instance.. Since plasmas are conventional matter with a small percentage of ionized particles, they do not conform to kinetic energy principles, alone. Rather, matter in the plasma state is strongly influenced by electromagnetism, and does not obey any other force, including gravity, except peripherally. Many types of instability are observed in plasma: diocotron instabilities, kink instabilities, edge instabilities (that make fusion reactors impossible to control), sausage instabilities (deformations in plasma flow), reactive instabilities, etc.. A principle tenet of Electric Universe theory is that various plasmas (mostly hydrogen ions and helium nuclei) comprise 99.99% of the ...
TY - JOUR. T1 - UAP56/DDX39B is a major cotranscriptional RNA-DNA helicase that unwinds harmful R loops genome-wide. AU - Pérez-Calero, Carmen. AU - Bayona-Feliu, Aleix. AU - Xue, Xiaoyu. AU - Barroso, Sonia I.. AU - Muñoz, Sergio. AU - González-Basallote, Víctor M.. AU - Sung, Patrick. AU - Aguilera, Andrés. PY - 2020/7. Y1 - 2020/7. N2 - Nonscheduled R loops represent a major source of DNA damage and replication stress. Cells have different ways to prevent R-loop accumulation. One mechanism relies on the conserved THO complex in association with cotranscriptional RNA processing factors including the RNA-dependent ATPase UAP56/DDX39B and histone modifiers such as the SIN3 deacetylase in humans. We investigated the function of UAP56/DDX39B in R-loop removal. We show that UAP56 depletion causes R-loop accumulation, R-loop-mediated genome instability, and replication fork stalling. We demonstrate an RNA-DNA helicase activity in UAP56 and show that its overexpression suppresses R loops and ...
Genomic Instability and Radiation Risk in Molecular Pathways to Colon Cancer. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Reproduction is a critically important event in every animals life and in all vertebrates is controlled by the brain via the hypothalamic-pituitary-gonadal (HPG) axis. In many species, this axis, and hence reproductive fitness, can be profoundly influenced by the social environment. Here, we review how the reception of information in a social context causes genomic changes at each level of the HPG axis. ©2011 Int. Union Physiol. Sci./Am. Physiol. Soc.
Deciphering how efficient and faithful replication of the human genome is achieved within the highly-complex, dynamic, and reactive environment of the nucleus. Identifying pathways for genomic instability in humans, identifying novel oncogenic drug targets, developing better chemotherapeutic treatments for human cancers caused by genomic instability.. ...
Several lines of evidence indicate that the functional status of telomeres is mechanistically related to the growth potential of normal and cancerous cells. Pre...
An experiment is performed to assess the prevalence of instability in univariate and bivariate macroeconomic time series relations and to ascertain whether various adaptive forecasting techniques successfully handle any such instability. Formal tests for instability and out-of-sample forecasts from sixteen different models are computed using a sample of 76 representative U.S. monthly postwar macroeconomic time series, constituting 5700 bivariate forecasting relations. The tests indicate widespread instability in univariate and bivariate autoregressive models. However, adaptive forecasting models, in particular time varying parameter models, have limited success in exploiting this instability to improve upon fixed-parameter or recursive autoregressive forecasts. ...
Transcription and replication are the two major DNA metabolic processes in cells. Both machineries involve large protein complexes progressing along the DNA at high speed and for long distances. Importantly, a large body of evidence suggests that encounters between DNA and RNA polymerases can induce replication fork arrest, DNA breaks, recombination intermediates and mutations, thereby causing genetic instability1-3. However, their role how they affect the underlying chromatin structure and cause epigenetic instability is largely unexplored ...
Correspondence re: Zimonjic et al. 2001. Derivation of human tumor cells in vitro without widespread genomic instability. Cancer Res no. 61 (24):8838-44. Submitted to Cancer Research 8/19/2002, r... Read It Review It ...
Author: Perry Nickelston. Title: Five Hidden Signs of Instability. Summary: If you work with patients long enough, you come to realize a few in-the-trenches facts. Here are five biggies that require constant consideration...
Trouvez tous les livres de Schmeidler, Lacey - Instability, Liquidity and World Money. Sur eurolivre.fr,vous pouvez commander des livres anciens et neufs.COMPARER ET acheter IMMÉDIATEMENT au meilleur prix. 9783845404103
that instability can occur even after the full establishment of the primary flow. Chandrasekhars method is used in the analysis and the relationship between the stability parameter and the wave number of the disturbance for neutral stability is obtained.--Page 1 ...
Problems that arise during DNA replication can drive genomic alterations that are instrumental in the development of cancers and many human genetic disorders. Replication fork barriers are a commonly encountered problem, which can cause fork collapse and act as hotspots for replication termination.
Estrogen-mediated high reactive oxygen species (ROS) tolerance plays an important role in driving carcinogenesis. ROS overproduction acts as the significant effector to increase genomic instability...
History Gene amplification is a frequent manifestation of genomic instability that plays a role in tumour progression and development of drug resistance. formation of micronuclei or nuclear buds which correlated with the removal of and increased sensitivity to MTX. These Indoximod findings indicate for the first time that NHEJ plays a specific role in DM formation and that increased MTX sensitivity of DM-containing cells depleted of DNA-PKcs results from removal. Conversely in HSR-containing cells we found no significant switch in the expression of NHEJ proteins. Depletion of DNA-PKcs experienced no effect on amplification and resulted in only a modest increase in sensitivity to MTX. Interestingly both DM-containing and HSR-containing cells exhibited decreased proliferation upon DNA-PKcs depletion. Conclusions We demonstrate a novel specific role for NHEJ in the formation of DMs but not HSRs in MTX-resistant cells and that NHEJ may be Indoximod targeted for the treatment of MTX-resistant colon ...
Locale, Genomes and Genes, Species, Research Topics, Publications, Scientific Experts about Experts and Doctors on genomic instability in Copenhagen, Capital Region, Denmark
The molecular defects responsible for tumor cell hypermutability in humans have not yet been fully identified. Here the gene encoding a G/T mismatch-binding protein (GTBP) was localized to within 1 megabase of the related hMSH2 gene on chromosome 2 and was found to be inactivated in three hypermutable cell lines. Unlike cells defective in other mismatch repair genes, which display widespread alterations in mononucleotide, dinucleotide, and other simple repeated sequences, the GTBP-deficient cells showed alterations primarily in mononucleotide tracts. These results suggest that GTBP is important for maintaining the integrity of the human genome and document molecular defects accounting for variation in mutator phenotype. ...
A summary of the 2nd NO-Age International symposium: Genomic instability in human brain Amund Hov[1], Ruben Gudmundsrud[1], Brian C. Gilmour[1], Hilde L. Nilsen[1][2], Jon Storm-Mathisen[1][3], Linda H. Bergersen[1][4][5], Evandro F. Fang[1][2][1] The Norwegian Centre on Healthy Ageing (NO-Age), Norway[2] Department of Clinical Molecular Biology, University of Oslo and Akershus University Hospital, 1478 Lørenskog, Norway[3] Amino Acid…
The concept of programmed cell death has been increasingly considered from various aspects since early 1970s. Primarily, knowledge of apoptosis referred to morphological changes in which chromatin is condensed and increasingly fragmented, revealed as small structure in the nucleus. The membrane shrinks and the cell becomes dense as can be seen by flow cytometry. Interestingly, similar modes of cell deletion were observed in nematodes indicating that apoptosis is a highly conserved machinery. Three Caeonorhabditis elegans gene products are found to have high homology with mammalian apoptotic genes: CED-9 inhibits apoptosis and is related to bcl-2; CED-3 and CED-4 promote apoptosis and are related to caspase 9 and APAF-1. Apoptosis is not accidental death, but a highly controlled and medically important molecular process. More general terms such as physiological or regulated cell death cover different morphologies and sequences. Programmed suicide of cells that were subjected to toxic exogenous and
Avgustinova A, Symeonidi A, Castellanos A, Urdiroz-Urricelqui U, Solé-Boldo L, Martín M, Pérez-Rodríguez I, Prats N, Lehner B, Supek F, Benitah SA ...
wrong paths and the others of minutes and new runs. After refining actions and conflicting iBooks to send the Flash browser, CREATIONS and positions ve displayed in web. The new pursuit of the it is parsing process permissions with Adobe AIR, leading political Tunes, and developing with selected time permissions.
Structures of thin films bonded on thick substrates are abundant in biological systems and engineering applications. Mismatch strains due to expansion of the films or shrinkage of the substrates can induce various modes of surface instabilities such as wrinkling, creasing, period doubling, folding, ridging, and delamination. In many cases, the film-substrate structures are not flat but curved. While it is known that the surface instabilities can be controlled by film-substrate mechanical properties, adhesion and mismatch strain, effects of the structures curvature on multiple modes of instabilities have not been well understood. In this paper, we provide a systematic study on the formation of multimodal surface instabilities on film-substrate tubular structures with different curvatures through combined theoretical analysis and numerical simulation. We first introduce a method to quantitatively categorize various instability patterns by analyzing their wave frequencies using fast Fourier ...
COVER Electron micrograph showing a stalled DNA replication fork in a checkpoint-defective yeast mutant. Aberrant DNA replication is one mechanism postulated to contribute to genome instability. The molecular basis of genome instability and its role in cancer development are the subject of a special feature in this issue. See page 599 [Image: J. M. Sogo et al.] ...
The protein PRC1, a telltale sign in many cancer types including prostate, ovarian, and breast cancer, act as a viscous glue during cell division, precisely controlling the speed at which two sets of DNA are separated as a single cell divides. The finding could explain why too much or too little PRC1 disrupts that process and causes genome errors linked to cancer.
Over a century ago, centrosome aberrations were postulated to cause cancer by promoting genome instability. The mechanisms governing centrosome assembly and function are increasingly well understood, allowing for a timely reappraisal of this postulate. This Review discusses recent advances that shed …
Persistent genetic instability in cancer cells induced by non-DNA-damaging stress exposures.s profile, publications, research topics, and co-authors
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
Instabilities in polymer processing limit production rates and may influence to some degree the optical or mechanical properties of the final product. One prominent example is the fountain flow instability, which takes place during the mold filling stage of an injection molding process. Old car bumpers which show light and dark lines are a famous example of an injection molded part in which such an instability occurred.
High dose ionizing radiation (IR) is a well-known risk factor for breast cancer but the health effects after low-dose (LD, |10 cGy) exposures remain highly uncertain. We explored a systems approach that compared LD-induced chromosome damage and transcriptional responses in strains of mice with genetic differences in their sensitivity to radiation-induced mammary cancer (BALB/c and C57BL/6) for the purpose of identifying mechanisms of mammary cancer susceptibility. Unirradiated mammary and blood tissues of these strains differed significantly in baseline expressions of DNA repair, tumor suppressor, and stress response genes. LD exposures of 7.5 cGy (weekly for 4 weeks) did not induce detectable genomic instability in either strain. However, the mammary glands of the sensitive strain but not the resistant strain showed early transcriptional responses involving: (a) diminished immune response, (b) increased cellular stress, (c) altered TGFβ-signaling, and (d) inappropriate expression of developmental
Some aging theories such as the Hallmarks of aging implicate DNA damage as one of the primary driving processes of aging contributing to genomic instability.
Video created by Johns Hopkins University for the course Introduction to the Biology of Cancer. Now, well turn our attention to the genetics of cancer, variation and mutation, two-hit hypothesis, and genomic instability.
Video created by Johns Hopkins University for the course Introduction to the Biology of Cancer. Now, well turn our attention to the genetics of cancer, variation and mutation, two-hit hypothesis, and genomic instability. 2000+ courses from ...
The Jackson Laboratory, which has had an NCI-designated Cancer Center since 1983, has research programs studying cancer initiation and progression, cancer cell genomic architecture, cancer genome instability and repair, and more.
For the function of evaluating the combustion instability of Ariane strong booster equally experimental and numerical operate was carried out in the f
Eros Di Giorgio, Harikrishnareddy Paluvai, Emiliano Dalla, Liliana Ranzino, Alessandra Renzini, Viviana Moresi, Valentina Cutano, Raffaella Picco, Claudio Brancolini
This media is available to current ISAKOS Members only. ISAKOS Members can log in to access all Global Link content. Non-Members can join ISAKOS today to gain full access to Global Link and all of the other ISAKOS Member benefits. ...
is negative, one expects curvature instabilities of the membrane and, in turn, these instabilities generate a pattern of domains that differ both in composition and in local curvature. Scaling arguments motivate the study of the family of singular perturbed energies ...
P.M. Lushnikov, Dva mekhanizma vozbuzhdeniya poverkhnostnykh voln: neustoichivost Kelvina-Gelmgoltsa i neustoichivost Mailsa, Izv. AN. Fizika Atmosfery i Okeana, 34, 413-421 (1998) [P.M. Lushnikov, Two mechanisms of surface waves generation: Kelvin-Helmholtz instability and Miles instability, Izvestiya, Atmospheric and Oceanic Physics (1998)]. ...
Strategies the pa- tient has used to reduce risk for infection are identified.1994; Zwangersschap and Shine, 1992; Mishima et al.
2019 marks a year of instability and uncertainty reflected in the field of potential best picture nominees, from Parasite to Joker.
You hindquarters look at with hormonal instability by managing your every day accentuate level, feeding a ... lasting, that feels eff it or non is.
Abbas T, Keaton MA, Dutta A (March 2013). "Genomic instability in cancer". Cold Spring Harbor Perspectives in Biology. 5 (3): ... Barlow JH, Nussenzweig A (December 2014). "Replication initiation and genome instability: a crossroads for DNA and RNA ... and proceeds in a bidirectional manner until all genomic DNA is replicated. Despite the fundamental nature of these events, ... it has been shown that many organisms use preferred genomic regions as origins. The necessity to regulate origin location ...
... also known as genome instability. Genomic integrity is now appreciated at several levels where some tumors display instability ... In breast cancer, the genetic form characterized by the BRCA-1 gene exhibits greater levels of genomic instability than ... Grady, William M. (2004). "Genomic instability and colon cancer". Cancer and Metastasis Reviews. 23 (1-2): 11-27. doi:10.1023/A ... BUB1 and BUBR1 and amplification of STK15 are key regulators that have been implicated in the genomic instability resulting in ...
... and Genomic Instability, Epigenetics and Metabolism. Five shared research facilities (SRFs) provide services to support ... Delivery and Translational Therapeutics Genomic Instability, Epigenetics and Metabolism Markey Cancer Center has particularly ...
Gonzalo S, Kreienkamp R (2016). "Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted ... Wu H, Roks AJ (2014). "Genomic instability and vascular aging: a focus on nucleotide excision repair". Trends Cardiovasc. Med. ... "Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell. 124 (2): 315-29. doi:10.1016/j.cell. ... "Increased genomic instability is not a prerequisite for shortened lifespan in DNA repair deficient mice". Mutat. Res. 596 (1-2 ...
Radiation-Induced Genomic Instability and Bystander Effects Clastogenic Factors and Transgenerational Effects". Radiation ... CS1 maint: discouraged parameter (link) Busby, Chris (17 March 2016). "It's not just cancer! Radiation, genomic instability and ... "Increased genomic instability in somatic cells of the progeny of female mice exposed to acute X-radiation in the ... It has been shown that radiation damage including genome instability and carcinogenesis may occur transgenerationally in both ...
"Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864. S2CID ... Gonzalo S, Kreienkamp R (2015). "DNA repair defects and genome instability in Hutchinson-Gilford Progeria Syndrome". Curr. Opin ...
Thus, individuals with RecQ-associated PS show an increased risk of developing cancer, which is caused by genomic instability ... On the cellular level, cells of affected individuals exhibit chromosomal abnormalities, genomic instability, and sensitivity to ... "Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864. S2CID ... There are two subpathways for NER, which differ only in their mechanism for recognition: global genomic NER (GG-NER) and ...
Additionally, CDK6 might be altered through genomic instability, a mechanism of downregulation of tumor suppressor genes; this ... Negrini S, Gorgoulis VG, Halazonetis TD (Mar 2010). "Genomic instability--an evolving hallmark of cancer". Nature Reviews ...
"Genomic instability in laminopathy-based premature aging". Nature Medicine. 11 (7): 780-785. doi:10.1038/nm1266. PMID 15980864 ... Recent genomic studies have confirmed that the genes involved in growth hormone uptake and signaling are largely conserved ...
Patients also don't have appropriate DNA repair, and they also have increased genomic instability. In normal conditions, the ... "Genomic instability in laminopathy-based premature aging". Nature Medicine. 11 (7): 780-785. doi:10.1038/nm1266. PMID 15980864 ...
"Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864. Chen L, ...
Gonzalo S, Kreienkamp R (2016). "Methods to Monitor DNA Repair Defects and Genomic Instability in the Context of a Disrupted ... "Genomic instability and aging-like phenotype in the absence of mammalian SIRT6". Cell. 124 (2): 315-29. doi:10.1016/j.cell. ... "Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864. S2CID ... Singh DK, Ahn B, Bohr VA (2009). "Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging". ...
May 2002). "Genomic instability in mice lacking histone H2AX". Science. 296 (5569): 922-7. Bibcode:2002Sci...296..922C. doi: ... January 2005). "Genomic maps and comparative analysis of histone modifications in human and mouse". Cell. 120 (2): 169-81. doi: ... In contrast mature sperm cells largely use protamines to package their genomic DNA, most likely because this allows them to ...
"Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864. Yozef ...
"Genomic instability in laminopathy-based premature aging". Nature Medicine. 11 (7): 780-785. doi:10.1038/nm1266. PMID 15980864 ... This concept stems from a comparative analysis of genomic stability in mammalian cells. One opposing argument is based on ... Bloom syndrome is a rare autosomal recessive disorder that is characterized by short stature, chromosomal instability, ...
Yeo, RA; Hill, D; Campbell, R; Vigil, J; Brooks, WM (2000). "Developmental instability and working memory ability in children: ... Graham, J. H. (1992). "Genomic coadaption and development stability in hybrid zones". Acta Zool. Fenn. 191: 121-132. Graham, J ... Fluctuating asymmetry (FA) is often considered to be the product of developmental stress and instability, caused by both ... May 2002). "The sound of symmetry: Voice as a marker of developmental instability". Evolution and Human Behavior. 23 (3): 173- ...
Genomic instability is a common feature of cancer; therefore understanding structural and chromosomal abnormalities can give ...
Cold Spring Harbor Laboratory (2007). "Human RecQ Helicases, Homologous Recombination And Genomic Instability". ScienceDaily. ... When two or more viruses, each containing lethal genomic damage, infect the same host cell, the virus genomes can often pair ...
Alderton GK (March 2011). "Genomic instability: Expanding the reach of Fanconi anaemia". Nat. Rev. Cancer. 11 (3): 158-159. doi ...
The resulting genomic instability directly contributes to carcinogenesis. Cellular transformation leads to cancer and ...
"Polycomb Repressor Complex 2 in Genomic Instability and Cancer". Int J Mol Sci. 18 (8): 1657. doi:10.3390/ijms18081657. PMC ... PRC2 is required for initial targeting of genomic region (PRC Response Elements or PRE) to be silenced, while PRC1 is required ...
... mutations in caretaker genes lead to genomic instability. Tumor cells arise from two distinct classes of genomic instability: ... In addition to providing genomic stability, caretakers also provide chromosomal stability. Chromosomal instability resulting ... mutational instability arising from changes in the nucleotide sequence of DNA and chromosomal instability arising from improper ... Michor, F; Iwasa, Y; Komarova, N. L.; Nowak, M. A. (2003). "Local regulation of homeostasis favors chromosomal instability". ...
"Hypoxia and defective apoptosis drive genomic instability and tumorigenesis". Genes & Development. 18 (17): 2095-107. doi: ... Genomic amplification occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one ... Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the ... Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability ...
"Hypoxia and defective apoptosis drive genomic instability and tumorigenesis". Genes Dev. 18 (17): 2095-107. doi:10.1101/gad. ... Fernandez PC, Frank SR, Wang L, Schroeder M, Liu S, Greene J, Cocito A, Amati B (May 2003). "Genomic targets of the human c-Myc ...
... contributors to genomic instability". Seminars in Cancer Biology. 20 (5): 320-8. doi:10.1016/j.semcancer.2010.10.010. PMC ...
Nemec AA, Wallace SS, Sweasy JB (October 2010). "Variant base excision repair proteins: contributors to genomic instability". ... of HNSCC contain genomic DNA from HPV, and the association varies based on the site of the tumor, especially HPV-positive ...
Veneti Z, Gkouskou KK, Eliopoulos AG (July 2017). "Polycomb Repressor Complex 2 in Genomic Instability and Cancer". Int J Mol ... evidenced from interspecies genomic sequence alignments. The X chromosome is notably larger and has a more active euchromatin ... "A systems biology approach to identify intelligence quotient score-related genomic regions, and pathways relevant to potential ...
Veneti Z, Gkouskou KK, Eliopoulos AG (July 2017). "Polycomb Repressor Complex 2 in Genomic Instability and Cancer". Int J Mol ... "A proximal conserved repeat in the Xist gene is essential as a genomic element for X-inactivation in mouse". Development. 136 ( ...
Nemec AA, Wallace SS, Sweasy JB (Oct 2010). "Variant base excision repair proteins: contributors to genomic instability". ... Hagen L; Peña-Diaz J; Kavli B; Otterlei M; Slupphaug G; Krokan HE (August 2006). "Genomic uracil and human disease". Exp. Cell ...
Oberdoerffer P, Sinclair DA (September 2007). "The role of nuclear architecture in genomic instability and ageing". Nature ... Veneti Z, Gkouskou KK, Eliopoulos AG (July 2017). "Polycomb Repressor Complex 2 in Genomic Instability and Cancer". ... PRC-mediated epigenetic aberrations are linked to genome instability and malignancy and play a role in the DNA damage response ...
Comparative genomic hybridization[edit]. Comparative genomic hybridization can be described as a method that uses FISH in a ... "Chromosomal instability in gastric mucosa-associated lymphoid tissue lymphomas: A fluorescent in situ hybridization study using ... "Comparative Genomic Hybridization". McGraw-Hill Dictionary of Scientific and Technical Terms. Retrieved September 19, 2013.. ... Genomic libraries are often named after the institution in which they were developed. An example being the RPCI-11 library, ...
Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis.[51] ... indicating that genomic instability plays an important role in the carcinogenesis of this tumor type.[53][54][55][56] ... "MicroRNAs down-regulate homologous recombination in the G1 phase of cycling cells to maintain genomic stability". Elife. 3 ...
"Genomic instability in mice lacking histone H2AX". Science. 296 (5569): 922-7. Bibcode:2002Sci...296..922C. doi:10.1126/science ... "Genomic maps and comparative analysis of histone modifications in human and mouse". Cell. 120 (2): 169-81. doi:10.1016/j.cell. ... 939 In contrast mature sperm cells largely use protamines to package their genomic DNA, most likely because this allows them to ...
"Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability?". Cell Cycle 4 (11): 1465- ...
Lindahl T (Apr 1993). "Instability and decay of the primary structure of DNA". Nature. 362 (6422): 709-15. Bibcode:1993Natur. ... circular structure, which assures complete replication without genomic tags;. *structural periodicity, which permits modular ...
DNA methylation occurs on the cytosine of CpG dinucleotides in the genomic sequence, and protein methylation occurs on the ... and gain instability.[85] Phenylbutyrate has also been shown to increase histone acetylation, decrease histone methylation, ...
... and genomic instability in lymphocytes". The Journal of Experimental Medicine. 207 (6): 1145-52. doi:10.1084/jem.20091245. PMC ... The current gold standard for diagnosis is genomic DNA sequence analysis, which can detect WAS and the related disorders XLT ...
If damaged DNA is left unrepaired, it can lead to cell death or genomic instability, cancer and other pathologies.[23] ...
"NIH, Lacks family reach understanding to share genomic data of HeLa cells". The National Institutes of Health. August 7, 2013. ... does not fulfill the criteria for an independent unicellular asexually reproducing species because of the notorious instability ... Numerical and structural chromosomal aberrations identified by SKY, genomic imbalances detected by CGH, as well as FISH ... "The genomic and transcriptomic landscape of a HeLa cell line". G3: Genes, Genomes, Genetics. 3 (8): 1213-24. doi:10.1534/ ...
The high mutation frequencies in carcinomas reflect the genome instability characteristic of cancers.[citation needed] ... "Genomic sequencing in cancer". Cancer Lett. 340 (2): 161-70. doi:10.1016/j.canlet.2012.11.004. PMC 3622788. PMID 23178448 ... "Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6" ...
Dang CV, Li F, Lee LA, Could MYC induction of mitochondrial biogenesis be linked to ROS production and genomic instability? ( ...
... thus increasing genomic instability.[37] MCPH1 facilitation of the DNA damage response appears to be necessary for proper ... and displayed chromosomal instability in a micronucleus test.[29] ...
"Hypoxia and defective apoptosis drive genomic instability and tumorigenesis". Genes & Development. 18 (17): 2095-107. doi: ... Genomic amplification occurs when a cell gains copies (often 20 or more) of a small chromosomal locus, usually containing one ... Disruption of a single gene may also result from integration of genomic material from a DNA virus or retrovirus, leading to the ... Such alterations are thought to occur early in progression to cancer and to be a likely cause of the genetic instability ...
"Genomic instability in laminopathy-based premature aging". Nat. Med. 11 (7): 780-5. doi:10.1038/nm1266. PMID 15980864.. ... which is caused by genomic instability and increased rates of mutation.[7] ... conserved ATP-dependent helicases required for repairing DNA and preventing deleterious recombination and genomic instability.[ ... There are two subpathways for NER, which differ only in their mechanism for recognition: global genomic NER (GG-NER) and ...
Alternatively, the leveling off of frequency of micronuclei in older subjects would suggest a threshold of genomic instability ... However, higher micronuclei frequency corresponds to a decreased efficiency of DNA repair and increased genomic instability, ... It usually is a sign of genotoxic events and chromosomal instability. Micronuclei are commonly seen in cancerous cells and may ... centromere instability, and facial anomalies syndrome) or after treatment by DNA methyl transferase inhibitors. Since assembly ...
Absence of cytosolic SOD causes a dramatic increase in mutagenesis and genomic instability. Mice lacking mitochondrial SOD ( ...
Hypoxia and defective apoptosis drive genomic instability and tumorigenesis»։ Genes & Development 18 (17): 2095-107։ September ... Differing patterns of genetic instability in mice deficient in the mismatch repair genes Pms2, Mlh1, Msh2, Msh3 and Msh6»։ ... Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability»։ Carcinogenesis (review) 30 (7): ...
Malignant tumors are also characterized by genome instability, so that cancers, as assessed by whole genome sequencing, ... "Genomic sequencing in cancer". Cancer Lett. 340 (2): 161-70. doi:10.1016/j.canlet.2012.11.004. PMC 3622788. PMID 23178448 ...
Studies show that in cases of cancer and other genomic instability, higher levels of EEs can be observed. Mitochondrial DNA can ... Sometimes called EEs, extrachromosomal elements, have been associated with genomic instability in eukaryotes. Small ... Extrachromosomal circular DNA (eccDNA) is present in all eukaryotic cells, is usually derived from genomic DNA, and consists of ... Double minute chromosomes (DMs) are also extrachromosomal elements that are associated with genome instability. DMs are ...
Epigenetic reductions of DNA repair enzyme expression may likely lead to the genomic and epigenomic instability characteristic ... The Colorectal Cancer Atlas integrating genomic and proteomic data pertaining to colorectal cancer tissues and cell lines have ... a survey of current practices and re-evaluation of the role of microsatellite instability testing". Modern Pathology. 31 (11): ... "High microsatellite instability (MSI-H) colorectal carcinoma: a brief review of predictive biomarkers in the era of ...
"Hypoxia and defective apoptosis drive genomic instability and tumorigenesis". Genes & Development 18 (17): 2095-107. doi: ...
However, mostly because of the marker's instability and tendency to be lost during cell division (mitosis), some cells are ... "The comorbidity of autism with the genomic disorders of chromosome 15q11.2-q13.1". Neurobiology of Disease. 38 (2): 181-191. ... "High-resolution molecular characterization of 15q11-q13 rearrangements by array comparative genomic hybridization (array CGH) ...
... postural instability, and reductions in aerobic capacity. Over time these deconditioning effects can impair astronauts' ... "Multi-drug resistant Enterobacter bugandensis species isolated from the International Space Station and comparative genomic ...
2005). "Repeat instability: mechanisms of dynamic mutations". Nature Reviews Genetics. 6 (10): 729-742. doi:10.1038/nrg1689.. ... 2002). "Microsatellites: genomic distribution, putative functions and mutational mechanisms: a review". Mol. Ecol. 11 (12): ... This is likely due to homologous chromosomes with arms of unequal lengths causing instability during meiosis.[19] ... This involves searching the genomic DNA sequence for microsatellite repeats, which can be done by eye or by using automated ...
It started in Toledo in 1449, in a period of political instability, when King John I sent his constable Don Alvaro de Luna to ... "Human Genomic Diversity Where the Mediterranean Joins the Atlantic". Molecular Biology and Evolution. 37 (4): 1041-1055. doi ... "The genomic history of the Iberian Peninsula over the past 8000 years". Science. 363 (6432): 1230-1234. doi:10.1126/science. ...
Singh DK, Ahn B, Bohr VA (2009). "Roles of RECQ helicases in recombination based DNA repair, genomic stability and aging". ... Drescher KM, Sharma P, Lynch HT (2010). "Current hypotheses on how microsatellite instability leads to enhanced survival of ... These short repetitive sequences of DNA become unstable, leading to a state of microsatellite instability (MSI). Mutated ...
LINE1(L1) TE's and other retrotransposons have been linked to cancer because they cause genomic instability.[32] ... retrotransposition and genome instability". Cell. 110 (3): 277-80. doi:10.1016/S0092-8674(02)00868-1. PMID 12176313. ... TEs use a number of different mechanisms to cause genetic instability and disease in their host genomes. ... "Induction of Instability at Selected Loci in Maize".[8] ... which plays an important role in genomic evolution.[17]:284 ...
Genomic studiesEdit. An adenine (A) to cytosine (C) synonymous substitution at base 984 (i.e. A984C) in exon 3 of PTGIR' is the ... This instability makes defining the exact affinity of PGI2 for IP difficult. It also makes it important to have stable ...
"DNA tests probe the genomic ancestry of Brazilians". scielo.br.. *^ Valenzuela C. (1984). Marco de Referencia Sociogenético ... Chambers, Sarah C. (2003). "Little Middle Ground The Instability of a Mestizo Identity in the Andes, 18th and 19th centuries". ... Chambers, Sarah C. (2003). "Little Middle Ground The Instability of a Mestizo Identity in the Andes, 18th and 19th centuries". ... Another study, conducted by Mexico's National Institute of Genomic Medicine (INMEGEN), reported that mestizo Mexicans were ...
... Vassilis G. Gorgoulis Department of Histology and Embryology, Medical School, ...
This review summarizes the current body of evidence that mutp53 plays a role in promoting various forms of genomic instability ... Links between mutant p53 and genomic instability.. Hanel W1, Moll UM. ... and amplifications by multiple gain-of-function mechanisms leading to genomic instability that ultimately promotes tumor growth ... mechanisms through gain-of-function interactions with multiple proteins leading to a higher level of genomic instability than ...
In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. ... Two predominant forms of genomic instability that have been identified in colon cancer are microsatellite instability and ... Genomic and epigenetic instability in colorectal cancer pathogenesis.. Grady WM1, Carethers JM. ... Determining the causes and roles of genomic and epigenomic instability in colon tumor formation has the potential to yield more ...
β-Catenin promotes genomic instability. Marei Dose, Akinola Olumide Emmanuel, Julie Chaumeil, Jiangwen Zhang, Tianjiao Sun, ... β-Catenin promotes genomic instability. Marei Dose, Akinola Olumide Emmanuel, Julie Chaumeil, Jiangwen Zhang, Tianjiao Sun, ... β-Catenin induces T-cell transformation by promoting genomic instability Message Subject (Your Name) has sent you a message ... β-Catenin induces T-cell transformation by promoting genomic instability. Marei Dose, Akinola Olumide Emmanuel, Julie Chaumeil ...
Genomic Instability Within Centromeres of Interspecific Marsupial Hybrids Message Subject (Your Name) has forwarded a page to ... Genomic Instability Within Centromeres of Interspecific Marsupial Hybrids. Cushla J. Metcalfe, Kira V. Bulazel, Gianni C. ... Genomic Instability Within Centromeres of Interspecific Marsupial Hybrids. Cushla J. Metcalfe, Kira V. Bulazel, Gianni C. ... Genomic Instability Within Centromeres of Interspecific Marsupial Hybrids. Cushla J. Metcalfe, Kira V. Bulazel, Gianni C. ...
Transient excess of MYC activity can elicit genomic instability and tumorigenesis Message Subject (Your Name) has sent you a ... Transient excess of MYC activity can elicit genomic instability and tumorigenesis. Dean W. Felsher and J. Michael Bishop ... The brief surfeit of MYC activity was accompanied by evidence of genomic instability, including karyotypic abnormalities, gene ... MYC Induces Genomic Destabilization of NHF.. Because Rat1A cells do not exhibit cellular senescence, they may have genetic ...
Genomic Instability Induced by Mutations in Saccharomyces cerevisiae POL1. Pedro J. A. Gutiérrez and Teresa S.-F. Wang ... Genomic Instability Induced by Mutations in Saccharomyces cerevisiae POL1. Pedro J. A. Gutiérrez and Teresa S.-F. Wang ... Genomic Instability Induced by Mutations in Saccharomyces cerevisiae POL1. Pedro J. A. Gutiérrez and Teresa S.-F. Wang ... Genomic Instability Induced by Mutations in Saccharomyces cerevisiae POL1 Message Subject (Your Name) has forwarded a page to ...
The 2016 Gordon Research Seminar on Genomic Instability (GRS) will be held in Hong Kong, China. Apply today to reserve your ... The Gordon Research Seminar on Genomic Instability is a unique forum for graduate students, post-docs, and other scientists ... This GRS will be held in conjunction with the "Genomic Instability" Gordon Research Conference (GRC). Those interested in ... DNA replication and DNA repair is orchestrated for the maintenance of genomic integrity. Along with scientific talks and ...
DSB accumulation in injured epithelium led to impaired colonic healing and genomic instability. Targeted inhibition of miR-23a ...
Induction of genomic instability by PMN-MP-derived miR-23a and miR-155. (A-D) Long-term coculture of IECs and PMN-MPs was ... Genomic instability--an evolving hallmark of cancer. Nat Rev Mol Cell Biol. 2010;11(3):220-228.. View this article via: PubMed ... Neutrophil-induced genomic instability impedes resolution of inflammation and wound healing. Veronika Butin-Israeli,1 Triet M. ... Since the loss of LB1 has been previously linked to DSB accumulation and genomic instability (26), these data suggest that PMN- ...
Chemical compound and disease context of Genomic Instability. *This preferential enhancement of genomic instability in ... Biological context of Genomic Instability. *Mismatch repair has a central role in maintaining genomic stability by repairing ... Disease relevance of Genomic Instability. *Fanconi anaemia (FA) is an autosomal-recessive disorder characterized by genomic ... Enhancement of genomic instability by 17beta-estradiol in minisatellite sequences of X-ray-transformed mouse 10T1/2 cells. ...
The MSK SPORE in Genomic Instability in Breast Cancer seeks to turn genomic instability into an advantage for therapeutic ... MSK SPORE in Genomic Instability in Breast Cancer More About MSK SPORE in Genomic Instability in Breast Cancer ... the goals are to take the risks of genomic instability (poor prognosis, rapid development of resistance) and turn genomic ... These profiles of genomic instability have offered novel insights about the drivers of breast cancer development and ...
Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions ... This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a ... Novel deletions causing pseudoxanthoma elasticum underscore the genomic instability of the ABCC6 region. *Laura MF Costrop1. , ... Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions ...
Estimation of genomic instability was carried out in blood cultures by test on chromosome aberration and micronuclei test with ... genomic instability. Special attention will be paid to the investigation how emotional state of parents and teachers im-pact on ... young childrens genomic instability. Methods. For evaluation of stress expression levels we used the complex of standard ... At the same time, the role of genome instability in processes of tumor induction and progression is proved very correctly. In ...
Now researchers at Baylor College of Medicine who study families with such genomic disorders have found a shared, yet unusual, ... Studying patients with another genomic disorder associated with the PLP1 gene, the researchers were able to find the same ... They also identified the genomic elements that produce such architecture, a finding that will help predict other unstable ... had a more severe constellation of symptoms associated with the genomic disorder. The patients required oxygen or a ventilator ...
PTTG induces genomic instability in thyroid cells. Dae Kim, Victor Lopes, Helen Pemberton, Anna Stratford, John C. Watkinson, ... PTTG induces genomic instability in thyroid cells. Dae Kim, Victor Lopes, Helen Pemberton, Anna Stratford, John C. Watkinson, ... PTTG induces genomic instability in thyroid cells. Dae Kim, Victor Lopes, Helen Pemberton, Anna Stratford, John C. Watkinson, ... The genomic instability index (GI-index) was 6.7-72.7% higher in cancers than normal, and in metastatic nodes from 2 patients ...
Defects in the DDR lead to genomic instability that is a characteristic of many rare human diseases, such as Ataxia ... Defects in the DDR lead to genomic instability that is a characteristic of many rare human diseases, such as Ataxia ... Microcephaly is a component of many rare human diseases, some of which are associated with DDR defects and genome instability. ... Targeting p38α Increases DNA Damage, Chromosome Instability, and the Anti-tumoral Response to Taxanes in Breast Cancer Cells ...
Defects in the DDR lead to genomic instability that is a characteristic of many rare human diseases, such as Ataxia ... Defects in the DDR lead to genomic instability that is a characteristic of many rare human diseases, such as Ataxia ... The study, performed by the Genomic Instability and Cancer Laboratory at IRB Barcelona, has been published in the journal Cell ... Microcephaly is a component of many rare human diseases, some of which are associated with DDR defects and genome instability. ...
Alternative perspectives on genomic instability and mechanisms that limit genomic instability tolerance. A, Snapshot of a ... Distinction between Intratumor Genetic Heterogeneity and Genomic Instability. *Therapeutic Interventions and the Genomic ... to push both subpopulations out of the critical range of genomic instability and into the range where genomic instability ... Genomic Instability in Cancer: Teetering on the Limit of Tolerance. Noemi Andor, Carlo C. Maley and Hanlee P. Ji ...
... J Environ Pathol Toxicol Oncol. 2003;22(3):179-99. doi: 10.1615/jenvpathtoxoncol.v22.i3.30. ... In this review, we summarize the growing evidence that deregulated c-myc expression generates genomic instability by initiating ... to which c-Myc contributes during its initiation and progression through the induction of genomic instability in critical genes ... Cancer is a disease of impaired genomic stability, ...
New evidence reveals that NPM-ALK translocation also impairs the ability of cells to maintain the genomic stability through ... Endogenous and exogenous factors compromise genomic stability and cause dysregulation in the DDR and DNA repair pathways. ... Genomic stability is crucial for cell life and transmitting genetic material is one of the primary tasks of the cell. The cell ... The Role of Oncogenic Tyrosine Kinase NPM-ALK in Genomic Instability Cosimo Lobello 1. , Vasilis Bikos 1, Andrea Janikova 2 and ...
... was used for detecting genomic instability in lung cancer tissues. DNAs from 20 lung cancer (18 non-small cell lung cancers and ... Genomic instability resulting in multiple mutations is believed to be a driving force in the carcinogenic process. In this ... Genomic instability resulting in multiple mutations is believed to be a driving force in the carcinogenic process. In this ... The ability to detect genomic instability in 20 cancer tissues by each single primer ranged from 15 to 75%. DNA changes were ...
... increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent ... Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis Ifigeneia V. Mavragani 1, Zacharenia ... "Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis." Cancers 9, no. 7: 91. ... Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis. Cancers. 2017; 9(7):91. ...
Proto-oncogene activation and genomic instability of cadmium-induced cell transformation in BALB/c-3T3 cells.. ... c-myc and c-jun and that some of the Cd-transformed cells may possess neoplastic potential resulting from genomic instability. ...
COBRE CBHD Seminar: Genomic and Epigenomic Instability in Cellular Senescence and Aging. Wednesday, September 11, 2019 ... Neretti will present his talk entitled "Genomic and Epigenomic Instability in Cellular Senescence and Aging". ...
A germline polymorphism of thymine DNA glycosylase induces genomic instability and cellular transformation.. [Ashley Sjolund, ... When expressed in cells, G199S induces genomic instability and cellular transformation. Together, these results suggest that ...
... of low LET radiation can induce genomic instability. The magnitude of genomic instability was measured as delayed chromosome ... from exposed mice at different times following irradiation were used as markers for radiation-induced genomic instability. A ... instability in bone marrow cells of exposed mice with different levels of endogenous DNA-dependent protein kinase catalytic ... of low LET radiation can induce genomic instability. The magnitude of genomic instability was measured as delayed chromosome ...
... and their levels are considered surrogate measures of genomic instability. Combined ,i,γ,/i,H2AX and SCE analysis was used to ... Temporal changes in genomic instability with in vitro culture were assessed when SCE analysis of four primary cell lines was ... To our knowledge, this is the first report of combined SCE and γH2AX analysis for the measurement of genomic instability in ... In support of the genomic instability suggested by their elevated SCE levels, γH2AX analysis also showed high levels of ...
Defects in these reactions lead to genomic instability, a confirmed driver of cancer and degenerative diseases. Fascinating and ... Cutting-edge concepts in translational, genomic, cellular, molecular, RNA and structural biology will be dissected to take the ...
Scientific Experts about Experts and Doctors on genomic instability in Copenhagen, Capital Region, Denmark ... Experts and Doctors on genomic instability in Copenhagen, Capital Region, Denmark. Summary. Locale: Copenhagen, Capital Region ... You are here: Locale , Denmark , Capital Region , Experts and Doctors on genomic instability in Copenhagen, Capital Region, ...
  • Substantial progress has been made to identify causes of chromosomal instability in colorectal cells and to determine the effects of the different forms of genomic instability on the biological and clinical behavior of colon tumors. (nih.gov)
  • All hybrids exhibited the same pattern of chromosomal instability and remodeling specifically within the centromeres derived from the maternal ( M. rufogriseus ) complement. (genetics.org)
  • Three areas are the focus of study: homologous recombination deficiency, chromosomal instability, and APOBEC mutagenesis. (mskcc.org)
  • Chromosomal instability, which does not necessarily have a unique pattern of mutations, is associated with a poor prognosis but no specific therapeutic strategy at present. (mskcc.org)
  • The link between chromosomal instability and innate immune signaling has been made, and the goal is to exploit this connection for therapy. (mskcc.org)
  • Interestingly, this did not induce a stable arrest, but aberrant cell-cycle progression associated with stalled DNA replication, rereplication and chromosomal instability, which was sufficient to increase the frequency of oncogenic transformation. (biologists.org)
  • This phenomenon is known as chromosomal instability and is often seen in cases of high-grade glioma in children. (elifesciences.org)
  • Background: Genomic DNA copy number aberrations are frequent in solid tumors, although the underlying causes of chromosomal instability in tumors remain obscure. (nyu.edu)
  • Conclusion: Many of the genes associated with higher frequency of copy number aberrations are direct targets of E2F, supporting the hypothesis that deregulation of the Rb pathway is a major contributor to chromosomal instability in breast tumors. (nyu.edu)
  • Chromosomal instability (CIN) is a type of genomic instability in which chromosomes are unstable, such that either whole chromosomes or parts of chromosomes are duplicated or deleted. (wikipedia.org)
  • Chromosomal instability is the most common form of genetic instability and cause of aneuploidy. (wikipedia.org)
  • This is especially true in low phenotype chromosomal instability, where the changes are subtle. (wikipedia.org)
  • A chromosomal instability assay should measure not only whole chromosome change rates, but also the partial chromosomal changes such as deletions, insertions, inversion and amplifications to also take into account segmental aneuploidies. (wikipedia.org)
  • This is because the fitness cost (survival to next generation) of chromosomal instability is lower in polyploid cells, as the cell has a greater number of chromosomes to make up for the chromosomal instability it experiences. (wikipedia.org)
  • Defects in the DDR lead to genomic instability that is a characteristic of many rare human diseases, such as Ataxia telangiectasia and Seckel Syndrome. (irbbarcelona.org)
  • Defects in these reactions lead to genomic instability, a confirmed driver of cancer and degenerative diseases. (science-community.org)
  • Here, we examine whether some events that lead to genomic instability (e.g., chromosome deletions, translocations, or loss) occur only after cells have first undergone a checkpoint arrest and subsequently have adapted to that arrest. (asm.org)
  • To examine the cellular changes occurring during the first 24 hours of exposure to a 50 Hz - magnetic field and to analyze whether the induced changes can lead to genomic instability in the progeny of the exposed cells . (emf-portal.org)
  • These events lead to genomic instability characterized by gross polyploidism and mitotic catastrophe. (elsevier.com)
  • Genomic and epigenetic instability in colorectal cancer pathogenesis. (nih.gov)
  • Two predominant forms of genomic instability that have been identified in colon cancer are microsatellite instability and chromosome instability. (nih.gov)
  • Determining the causes and roles of genomic and epigenomic instability in colon tumor formation has the potential to yield more effective prevention strategies and therapeutics for patients with colorectal cancer. (nih.gov)
  • The research projects proposed in this SPORE address genomic instability in breast cancer. (mskcc.org)
  • These profiles of genomic instability have offered novel insights about the drivers of breast cancer development and progression. (mskcc.org)
  • Cancer death as well as cancer rejuvenation observing in all countries stimulated our interest to revealing of the reasons of children's and adult's genomic instability. (scirp.org)
  • Cancer reflects the progressive accumulation of genetic alterations and subsequent genetic instability of cells. (aacrjournals.org)
  • The genomic instability index (GI-index) was 6.7-72.7% higher in cancers than normal, and in metastatic nodes from 2 patients were 104 & 225% greater than in the corresponding primary cancer. (aacrjournals.org)
  • Overall, we describe the first use of FISSR-PCR in human cancers, and demonstrate that the degree of instability strongly correlated with PTTG-expression in differentiated thyroid cancer. (aacrjournals.org)
  • Cancer is a disease of impaired genomic stability, to which c-Myc contributes during its initiation and progression through the induction of genomic instability in critical genes. (nih.gov)
  • Detection of genomic instability in lung cancer tissues by random amplified polymorphic DNA analysis. (cdc.gov)
  • In this study, the random amplified polymorphic DNA (RAPD) technique, a simple PCR-based DNA polymorphism assay system, was used for detecting genomic instability in lung cancer tissues. (cdc.gov)
  • These results seem to indicate that genomic rearrangement is associated with lung carcinogenesis and that RAPD analysis is useful for the detection of genomic instability in lung cancer tissues. (cdc.gov)
  • They have no known specific abnormalities (a notable exception is well-differentiated liposarcomas that frequently carry chromosome 12q amplification), and their complex karyotypes are believed to be the result of genomic instability, a hallmark of the cancer phenotype [ 6 ]. (hindawi.com)
  • Here we harness advances in DNA sequencing to annotate genomic rearrangements in 13 patients with pancreatic cancer and explore clonal relationships among metastases. (nih.gov)
  • Genomic instability frequently persists after cancer dissemination, resulting in ongoing, parallel and even convergent evolution among different metastases. (nih.gov)
  • These data attest to the richness of genetic variation in cancer, brought about by the tandem forces of genomic instability and evolutionary selection. (nih.gov)
  • These eroded telomeres are then recognized as substrates for DNA damage repair, stimulating the genomic instability that drives cancer progression. (bu.edu)
  • Therefore, the Laboratory of Genome instability and Cancer therapeutics is interested in understanding how normal telomeres are maintained, how dysfunctional telomeres arise, and how defects in this process contribute to the onset of cancer. (bu.edu)
  • Telomere dysfunction is a major source of genomic instability contributing to the development of human cancer. (bu.edu)
  • Genomic instability, a hallmark of cancer and aging, is defined as a high frequency of mutations within the genome [ 1 , 2 ]. (intechopen.com)
  • With the exception of cancer, genomic instability is widely associated with neurodegenerative disorders. (alliedacademies.org)
  • Objective: We sought to investigate various molecular subtypes defined by genomic instability that may be related to early death and recurrence in colon cancer. (uib.no)
  • To develop animal models that represent the broad spectrum of human prostate cancer, we created transgenic mice with targeted prostate-specific expression of two genes ( Eco RI and c- fos ) implicated in the induction of genomic instability. (oup.com)
  • Genomic instability is a hallmark of cancer associated with obesity. (tcd.ie)
  • Phenotypic circulating tumor cell (CTC) classifier of genomic instability (GI) associates with improved overall survival (OS) for metastatic castration-resistant prostate cancer (mCRPC) patients (pts) receiving platinum agents in addition to taxanes. (epicsciences.com)
  • Together, these findings support of a genome-centered evolutionary framework for cancer progression that emphasizes cell-to-cell genomic variability as the basis for macro-evolutionary selection and rapid phenotypic switching in response to new environments. (wayne.edu)
  • Genomic alterations of the proto-oncogene c-erbB-2 (HER-2/neu) are associated with aggressive behavior and poor prognosis in patients with breast cancer. (biomedcentral.com)
  • To assess the broader genomic implications of structural changes at the HER2 locus, we investigated relationships between genomic instability and HER2 status in patients with invasive breast cancer. (biomedcentral.com)
  • Genetic disorders associated with cancer predisposition and genomic instability. (ox.ac.uk)
  • The functional link between genomic instability and cancer is strengthened by the existence of several "genetic instability" disorders of humans that are associated with a moderate to severe increase in the incidence of cancers. (ox.ac.uk)
  • Analysis of the cells from such cancer-prone individuals is clearly a potentially fruitful approach for delineating the genetic basis for instability in the genome. (ox.ac.uk)
  • In this article, we review the clinical and cellular properties of genetic instability disorders associated with cancer predisposition. (ox.ac.uk)
  • Supporting this view, we observed that loss of DDX23 is a prevalent feature of adenoid cystic carcinoma, an aggressive salivary gland cancer with very limited treatment options mostly due to our incomplete understanding of its genomic foundations and molecular basis. (ul.pt)
  • We performed array comparative genomic hybridization in 29 primary tumors from high risk patients with breast cancer. (biomedcentral.com)
  • Our results provide a new insight into the genomic complexity of breast cancer. (biomedcentral.com)
  • We report a much higher percentage of chromothripsis than described previously in other cancers and this suggests that massive genomic rearrangements occurring in a single catastrophic event may shape many breast cancer genomes. (biomedcentral.com)
  • Finally, we observed differences in chromosomal breakage patterns between different clinical breast cancer subtypes, We show that a relatively simple approach to the analysis of genomic data (much less detailed than sequencing) can be very informative when used on highly purified tumor biopsies and can provide new insights into the biology of known clinical categories of breast cancer. (biomedcentral.com)
  • In the "Biological background" section we shall review the basic biological data, and in the section "Genomic instability and somatic cellular Darwinian evolution in cancer" we shall examine the evidence for GI as an initiating event in cancer. (biomedcentral.com)
  • We review this literature in the section "Genomic instability and somatic cellular Darwinian evolution in cancer" below. (biomedcentral.com)
  • Peripheral Blood Lymphocytes as In Vitro Model to Evaluate Genomic Instability Caused by Low Dose Radiation', Asian Pacific Journal of Cancer Prevention , 17(4), pp. 1773-1777. (waocp.org)
  • The Department of Molecular and Human Genetics and the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine are seeking an individual for faculty appointment at rank appropriate for achievement and experience, working in any organism on problems in genomic instability or other genetic topic. (sciencecareers.org)
  • Successful candidates will have strong basic research programs related to genetic/genomic stability or instability, genome organization, genomics including but not limited to DNA replication, repair, mutation, genome rearrangements, DNA damage response, mechanisms of heritability and evolution, studied in any organism from bacteria to human, and will join the Mechanisms in Cancer Evolution program in the Dan L Duncan Comprehensive Cancer Center. (sciencecareers.org)
  • Preserving telomere function, via expression of ectopic telomerase, prevents genomic instability and immortalization of cancer prone mammary epithelial cells while triggering telomere dysfunction by DNA damaging agents halts breast cancer cell growth, predominantly by induction of senescence. (grantome.com)
  • The data generated will contribute in a significant way to better understanding the relationships between telomere status, genomic stability and cellular fate of human mammary epithelial cells, likely leading to the development of new preventative and therapeutic strategies for breast cancer. (grantome.com)
  • book Cancer: Cell Structures, Carcinogens and Genomic Instability is the Yet new in staff. (ortho-cad.com)
  • While the book Cancer: Cell Structures, Carcinogens and Genomic Instability 2006 has never a sure one to download, it is aerospace that as numerical majors at the 18th education am first to find the section of online Government of their data for audio account and friction, resolve n't being how to Insure. (ortho-cad.com)
  • 25 October 1400), made as the Father of English book Cancer: Cell Structures, Carcinogens and Genomic Instability 2006, shows clearly sent the greatest personal award of the Middle Ages and was the new right to improve exposed in Poets' Corner of Westminster Abbey. (ortho-cad.com)
  • Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer. (cshl.edu)
  • Now, we'll turn our attention to the genetics of cancer, variation and mutation, two-hit hypothesis, and genomic instability. (coursera.org)
  • Genes likely to have genomic instability phenotypes when mutated (e.g. those involved in mitosis, replication, repair, and telomeres) are rarely mutated in chromosomally unstable sporadic tumors, even though such mutations are associated with some heritable cancer prone syndromes. (nyu.edu)
  • This review summarizes the current body of evidence that mutp53 plays a role in promoting various forms of genomic instability and provides an overview of current mechanistic proposals. (nih.gov)
  • Here, we use mutants that are defective in checkpoint adaptation to show that adaptation is important for achieving the highest possible viability after exposure to DNA-damaging agents, but it also acts as an entrée into some forms of genomic instability. (asm.org)
  • We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. (cshl.edu)
  • A, Tumor metapopulation fitness ( y -axis) is maximal when it consists of subpopulations with intermediate levels of genomic instability (critical range), defined as the proportion of the genome that is altered ( x -axis). (aacrjournals.org)
  • Similar to some other primary human tumors, the mutation of p53 correlates significantly with the presence of high levels of genomic instability in osteosarcomas. (caltech.edu)
  • Surprisingly, osteosarcomas harboring an amplification of the HDM2 oncogene, which inhibits the tumor-suppressive properties of p53, do not display high levels of genomic instability. (caltech.edu)
  • Melanomas have high levels of genomic instability that can contribute to poor disease prognosis. (garvan.org.au)
  • The variation in the levels of genomic instability amongst tumors prompted us to investigate whether alterations in processes/genes involved in maintenance and/or manipulation of the genome were associated with particular types of genomic instability. (nyu.edu)
  • Our results indicate that POL1 plays a role in ensuring genomic stability in several ways, since these mutant alleles of POL1 can induce a range of mutator phenotypes. (genetics.org)
  • Genomic stability is crucial for cell life and transmitting genetic material is one of the primary tasks of the cell. (mdpi.com)
  • Endogenous and exogenous factors compromise genomic stability and cause dysregulation in the DDR and DNA repair pathways. (mdpi.com)
  • New evidence reveals that NPM-ALK translocation also impairs the ability of cells to maintain the genomic stability through both DDR and DNA repair pathways. (mdpi.com)
  • Drugs for leukaemia or lymphoma therapy such as idelalisib, duvelisib and ibrutinib block PI3Kδ activity directly or indirectly, potentially affecting AID expression and, consequently, genomic stability in B cells. (selleckchem.com)
  • SETD2 methylates α-tubulin to mediate cytoskeletal remodeling and maintain genomic stability. (aacrjournals.org)
  • Genomic stability is a commitment of regulation and establishment of cell lines in organisms. (alliedacademies.org)
  • These serial events in the FA pathway are required for the maintenance of genomic stability and normal hematopoiesis. (nii.ac.jp)
  • In order to find vertebrate genes involved in those steps, which serve to maintain genome stability, we have used the zebrafish (Danio rerio) to perform a screen for genomic instability mutants that models this second hit. (elsevier.com)
  • These findings represent first steps in our long-term goal of developing the zebrafish as a vertebrate model for finding genes involved in the control of genomic stability in vertebrates. (elsevier.com)
  • Our first specific aim involves using a panel of hTERT mutants to define the mechanisms by which ectopic telomerase confers genomic stability in HME cells, focusing on the possibility of a telomere length-independent """"""""capping"""""""" event and assessing the role of telomere binding proteins in maintenance of genomic stability and overall telomere length/function. (grantome.com)
  • To investigate one mechanism by which aneuploidy could contribute to tumorigenesis, we examined the effects of aneuploidy on genomic stability. (cshl.edu)
  • The term "genomic instability" describes complex of various molecular mechanisms and their effects leading stable genome of normal cell to unstable, characteristic for tumors [1]. (scirp.org)
  • We also found that follicular thyroid tumors exhibited greater genetic instability than papillary tumors (27.6% (n = 9) versus 14.5% (n = 10), p = 0.03). (aacrjournals.org)
  • Consistent with this, p53 mutant cells have been shown to accumulate genomic alterations in cell culture, mouse models, and some human tumors. (caltech.edu)
  • In this study, we examined levels and patterns of allelic imbalance (AI) in primary breast tumors with and without HER2 gene amplification to 1) examine associations between amplification of the HER2 gene and global genomic instability and 2) identify chromosomal changes commonly observed in HER2 amplified tumors. (biomedcentral.com)
  • Specific Aim 2 is to characterize the mechanism of genomic instability using microsatellite, interphase FISH analysis, and exon sequencing of the golden gene in golden RPE cells from mosaic eyes and by similar analysis of p53 in gin-10-associated tumors. (elsevier.com)
  • Methods: We applied array comparative genomic hybridization (CGH) to the analysis of breast tumors. (nyu.edu)
  • Further, although loss of function instability phenotypes have been demonstrated for many of the genes in model systems, we observed enhanced expression of most genes in tumors, indicating that over expression, rather than deficiency underlies instability. (nyu.edu)
  • These results define a novel role for elevated Pim-1 expression in promoting genomic instability in human prostate tumors. (uab.edu)
  • Proposed pathways how mutant p53 promotes aneuploidy, translocations, and amplifications by multiple gain-of-function mechanisms leading to genomic instability that ultimately promotes tumor growth and metastasis. (nih.gov)
  • In addition to genomic instability, epigenetic instability results in the aberrant methylation of tumor suppressor genes. (nih.gov)
  • Our ultimate plan is to exploit tumor-specific vulnerabilities by virtue of their underlying genomic instability. (mskcc.org)
  • At the same time, the role of genome instability in processes of tumor induction and progression is proved very correctly. (scirp.org)
  • B, Fifty cells (circles) sampled from a heterogeneous tumor metapopulation consisting of two subclones of variable genomic instability (color bar). (aacrjournals.org)
  • and genomic instability and related molecular, cytogenetic, and chromosomal effects during tumor formation and progression to malignancy. (cancer.gov)
  • Results: We discriminated three breast tumor subtypes based on genomic DNA copy number alterations. (nyu.edu)
  • Thus, mutations of POL1 can induce a variety of mutator phenotypes and can be a source of genomic instability in cells. (genetics.org)
  • Topoisomerase II works by severing DNA across the double helix, and while this opens the DNA up for transcription, the scientists think it also might leave it vulnerable to permanent damage and be a source of genomic instability. (usc.edu)
  • Therefore, genome-wide hypomethylation drives genomic instability, causing aging-associated disease phenotypes. (intechopen.com)
  • Mutations of chromosome replication genes can be one of the early events that promote genomic instability. (genetics.org)
  • This analysis of H3-G34R mutant fission yeast provides mechanistic insight into how G34R mutation may promote genomic instability in glioma. (elifesciences.org)
  • This suggests that SEPT9-i1 may promote genomic instability through both cytokinesis and mitotic spindle defects which lead to chromosome missegregation. (elsevier.com)
  • The inability of ATM to impose a cell cycle arrest in response to DNA damage increases genomic instability. (garvan.org.au)
  • Using fluorescent inter-simple sequence repeat PCR and ABI377 sequencer we investigated the relationship between the degree of genetic instability and PTTG expression in normal and tumorous thyroid samples. (aacrjournals.org)
  • By measuring PTTG mRNA using quantitative-PCR we demonstrated a relationship between PTTG expression and the degree of genetic instability in thyroid cancers (R 2 = 0.80, p = 0.007). (aacrjournals.org)
  • To further investigate PTTG's role in genetic instability we transfected FTC133 thyroid follicular cells and observed increased genetic instability in cells over-expressing PTTG compared with vector-only controls (n = 3, GI-Index VO = 29.7 +/-5.2 vs. PTTG = 63.7 +/-6.4, p = 0.013). (aacrjournals.org)
  • Consistent with the strong positive correlation in vivo, we also observed a dose response in genetic instability and PTTG expression (GI-Index low dose (0.5μg DNA/ 6-well plate) PTTG = 15.3% +/-1.7 vs. high dose (2 μg DNA) PTTG = 50.8% +/-3.3, p = 0.006). (aacrjournals.org)
  • Furthermore, in vitro studies demonstrated up-regulation of PTTG in thyroid cells may drive genetic instability through suppression of a rad21-dependent DNA repair mechanism. (aacrjournals.org)
  • Conclusions: A high copy number variation phenotype is a strong predictor of early recurrence and death, and may indicate a dose-dependent relationship between genetic instability and outcome. (uib.no)
  • It is assumed that by identifying the underlying cause of genetic instability in these disorders, one can derive valuable information not only about the basis of particular genetic diseases, but also about the underlying causes of genomic instability in sporadic cancers in the general population. (ox.ac.uk)
  • This group has discovered that H-DNA and Z-DNA-forming sequences near the translocation breakpoint hotspots in the human c-MYC gene induce DSBs, resulting in high levels of genetic instability in mammalian cells. (grantome.com)
  • Hence, the objectives of this application are to determine the mechanisms involved in genetic instabilities at breakpoint hotspots associated with disease, and further the development of novel approaches to reduce genetic instability caused by environmental DNA damaging agents. (grantome.com)
  • The immediate goals are to test the hypotheses that non-B-DNA structures found in the BCL-2 and c-MYC breakpoint regions are implicated in genetic instability across species, and that DNA damage induced by environmental factors at these hotspots enhance their susceptibility to genomic instability. (grantome.com)
  • The following are proposed: 1) to measure non-B DNA-induced genetic instability in different species. (grantome.com)
  • Thus, the amount of DNA damage induced and repaired in non-B sequences will be measured, and the level of genetic instability induced by environmental agents at these fragile site """"""""hotspots"""""""" determined;and 3) to identify the genes/pathways that are involved in the genetic instability at non-B DNA sequences in the presence and absence of environmental carcinogens. (grantome.com)
  • Using a high-throughput screen gene products involved in DNA structure-induced genetic instability will be identified at genomic hotspots to begin to elucidate the pathways involved in genetic instability. (grantome.com)
  • We evaluated cell viability, reactive oxygen species (ROS) formation, endoplasmic reticulum (ER) stress, HO-1 expression and compartmentalization and cellular genetic instability. (oncotarget.com)
  • Surprisingly, inhibition of HO activity with SnMP (10μM) failed to increase BTZ sensitivity in MM cells whereas inhibition of HO-1 nuclear translocation by E64d, a cysteine protease inhibitor, increased sensitivity to BTZ and decreased genetic instability as measured by cytokinesis-block micronucleus assay. (oncotarget.com)
  • Because malignant progression frequently involves loss of genes that function in DNA repair, adaptation may promote tumorigenesis by allowing genomic instability to occur in the absence of repair. (asm.org)
  • Studying primitive cells called germ cells from a small roundworm known as Caenorhabditis elegans , Butuci and Michael found that ZGA-related genomic instability and DNA damage stems not from the increased transcription of genes once the system is in motion, but rather from the sudden change - when the zygotic genome's "switch" is suddenly flipped on. (usc.edu)
  • During ZGA, however, an enormous number of genes are being accessed very suddenly and all at once, spreading instability throughout the genome as the system jolts into motion. (usc.edu)
  • Mutations in genes such as p53 and p21 change the cellular response to genotoxic stress and may alter the balance between apoptosis and genomic damage. (uni-wuerzburg.de)
  • The current work exploits this characteristic of fission yeast rqh10 mutants in a screen for genes that normally promote replication associated genomic instability. (queensu.ca)
  • Methods: We sought to investigate various molecular subtypes defined by instability at microsatellites (MSI), changes in methylation patterns (CpG island methylator phenotype, CIMP) or copy number variation (CNV) in 8 genes. (uib.no)
  • Twelve ENU- induced genomic instability (gin), or somatic mutator mutations were isolated in this screen at a rate suggesting the potential existence of 200 such genes. (elsevier.com)
  • However, little is known about the mechanism(s) of the breakages on the translocated genes, why the DSBs tend to locate in certain genomic fragile site """"""""hotspots"""""""", and the effects of environmental agents on the genomic instability at these susceptible hotspots. (grantome.com)
  • Our objectives are to determine (i) whether the intrinsic instability of VNTRs has a permanent effect on alternative splicing, and (ii) whether induced genomic instability preferentially acts on VNTRs to affect the alternative splicing of the genes that harbor them. (usherbrooke.ca)
  • This meeting will focus on understanding how the complex interplay between chromatin organization, DNA replication and DNA repair is orchestrated for the maintenance of genomic integrity. (grc.org)
  • Cross-departmental workshop composed of students, postdocs, and faculty with shared interest in basic principles and emerging discoveries in genomic instability, DNA replication, recombination and repair. (openwetware.org)
  • H3-G34R mutants exhibit genomic instability and increased replication stress, including slowed replication fork restart, although DNA replication checkpoints are functional. (elifesciences.org)
  • The genomic DNA of eukaryotes is packaged into chromatin, which regulates all DNA transactions including transcription, replication and repair. (elifesciences.org)
  • The phenotypical consequences of these genetic modifications may be found in the microsatellite instability (MSI) and in the loss of heterozygosity (LOH), which generate the replication errors in positive phenotypes repeats. (eurekaselect.com)
  • The conflicts among the molecular mechanisms, such as replication, transcription, and translation are majorly responsible for the genomic instability, among which, transcription-replication conflict is well understood. (alliedacademies.org)
  • Replication fork stalling is a source of potentially tumourigenic genomic instability. (queensu.ca)
  • This would indicate the mutation of a gene that normally promotes genomic instability following replication fork stalling. (queensu.ca)
  • Therefore, there are more replication-independent EDSBs (RIND-EDSBs) located in methylated genomic regions. (biomedcentral.com)
  • Synthesis of daughter strands starts at discrete sites, termed replication origins, and proceeds in a bidirectional manner until all genomic DNA is replicated. (wikipedia.org)
  • However, the mere assessment of the extent of genomic changes, amplifications and deletions may reduce the complexity of genomic data observed by array comparative genomic hybridization (array CGH). (biomedcentral.com)
  • GLI2 induces genomic instability in human keratinocytes by inhibiting apoptosis. (qmul.ac.uk)
  • Instances of rapid genomic change can result from an increased mutation rate caused by genome destabilizing events, such as inter- and/or intraspecific hybridization or exposure to environmental mutagens and stress ( F ontdevila 1992 ). (genetics.org)
  • Collectively, these results point to an association of mutant BRCA2 with genomic instability and gene alteration in 9p23-24, in at least a subset of BRCA2 mutation carriers. (springer.com)
  • Here I review the data on transgenerational instability showing that radiation-induced instability in the germline of irradiated parents manifests in their offspring, affecting their mutation rates and some other characteristics. (springer.com)
  • The relationship between p53 mutation and genomic instability in human osteosarcoma is addressed in this report. (caltech.edu)
  • In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. (selleckchem.com)
  • The genomic integrity is analyzed at cellular checkpoints, usually leading to a delay in cell cycle progression if DNA was damaged. (uni-wuerzburg.de)
  • History Gene amplification is a frequent manifestation of genomic instability that plays a role in tumour progression and development of drug resistance. (antibodyassay.com)
  • This genomic instability-based model will be used to study the mechanisms involved in the early stages of prostate carcinogenesis and to investigate the nature of subsequent events necessary for the progression to advanced disease. (oup.com)
  • Our goal here was to better understand how SEPT9-i1 expression might contribute to genomic instability and malignant progression. (elsevier.com)
  • Genomic instability (GI) is a hallmark of tumorigenic progression and is observed as delayed genetic damage in the progeny of irradiated and unirradiated bystander cells. (ox.ac.uk)
  • Headquartered in Madrid, Spain, its scientific-medical team is professionally and scientifically accredited by the Spanish Association of Human Genetics, specializing in the development and application of high resolution genomic systems for reliable and accurate clinical diagnosis. (bioinformant.com)
  • Radisky, DC & Bissell, MJ 2006, ' Matrix metalloproteinase-induced genomic instability ', Current Opinion in Genetics and Development , vol. 16, no. 1, pp. 45-50. (elsevier.com)
  • Our results further illustrate the instability of the ABCC6 genomic region and stress the importance of screening for deletions in the molecular diagnosis of PXE. (nature.com)
  • Cutting-edge concepts in translational, genomic, cellular, molecular, RNA and structural biology will be dissected to take the conversation to unprecedented levels of depth and breadth. (science-community.org)
  • Based on this evidence, I hypothesize that in the human Phy-RIND-EDSBs, reduction is a molecular process that mediates the genome-wide hypomethylation driving genomic instability, which is a nidus pathogenesis mechanism of human body deterioration in aging-associated NCDs. (intechopen.com)
  • SEPT9-i1 expressing cells demonstrated dramatic chromosome segregation defects, centrosome amplification and cytokinesis defects, suggesting two possible molecular mechanisms contributing to the development of genomic instability. (elsevier.com)
  • MYC may also contribute to tumorigenesis by inducing genomic destabilization ( 9 - 12 ). (pnas.org)
  • We report that transient excess of MYC activity can promote tumorigenesis in an immortal rodent cell line and elicit genomic destabilization in both immortal rodent cell lines and in normal human fibroblasts. (pnas.org)
  • Microcephaly is a component of many rare human diseases, some of which are associated with DDR defects and genome instability. (irbbarcelona.org)
  • Here, we show that besides the premature mitotic entry phenotype, Wee1 mutant murine cells fail to complete mitosis properly and exhibit several additional defects that contribute to the deregulation of mitosis, allowing mutant cells to progress through mitosis at the expense of genomic integrity. (sigmaaldrich.com)
  • The mitotic and cytokinesis defects caused by SETD2 loss were independent of SETD2-dependent histone methylation, confirming that α-tubulin methylation is responsible for the observed genomic instability. (aacrjournals.org)
  • Genomic instability encompasses a wide spectrum of defects ranging from localized point mutations of one or a few DNA base pairs to large chromosomal rearrangements, such as deletions, amplifications, inversions, translocations, and aneuploidy. (cancer.gov)
  • The magnitude of genomic instability was measured as delayed chromosome instability in bone marrow cells of exposed mice with different levels of endogenous DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity, i.e. high (C57BL/6J mice), intermediate (BALB/cJ mice), and extremely low (Scid mice). (unt.edu)
  • As chromosome instability refers to the rate that chromosomes or large portions of chromosomes are changed, there should be comparisons between cells, or cell populations rather than looking at cells individually in order to determine chromosome instability. (wikipedia.org)
  • This provides a more accurate determination of the presence of chromosome instability. (wikipedia.org)
  • Genomic instability resulting in multiple mutations is believed to be a driving force in the carcinogenic process. (cdc.gov)
  • STSs fall into one of two large genomic classes: The first is characterised by known, specific abnormalities such as chromosomal translocations or gene mutations and comprises around 20% of STSs. (hindawi.com)
  • Previous studies indicate that this disease has a complex genomic landscape, with frequent copy number changes and point mutations, but genomic rearrangements have not been characterized in detail. (nih.gov)
  • In addition to the mutations and/or gene amplifications that appear to be a prerequisite for the acquisition of a neoplastic phenotype, human cancers exhibit other "markers" of genomic instability--in particular, a high degree of aneuploidy. (ox.ac.uk)
  • 11q23-24 loss was itself associated with increased genomic complexity in DDLS. (aacrjournals.org)
  • In summary, we show that PI3Kδ or Bruton's tyrosine kinase inhibitors increase genomic instability in normal and neoplastic B cells by an AID-dependent mechanism. (selleckchem.com)
  • Reducing PLK1 activity recovered the ATM-dependent checkpoint arrest, and over-expressing PLK1 was sufficient to overcome the checkpoint arrest and increase genomic instability. (garvan.org.au)
  • This study wanted to assess the importance of deletions and insertions in the ABCC6 genomic region, which is known to have a high recombinational potential. (nature.com)
  • We hypothesized that because of the documented instability of the ABCC6 genomic region, the unidentified mutant alleles remaining after direct sequencing and screening for the recurrent exon 23-29 deletion, may consist of deletions and/or insertions. (nature.com)
  • The brief surfeit of MYC activity was accompanied by evidence of genomic instability, including karyotypic abnormalities, gene amplification, and hypersensitivity to DNA-damaging agents. (pnas.org)
  • In this review, we summarize the growing evidence that deregulated c-myc expression generates genomic instability by initiating gene amplification (both intra- and extra-chromosomally), gene rearrangements, and karyotypic instability. (nih.gov)
  • These results suggest that cell transformation induced by Cd may be attributed, at least in part, to gene amplification of c-myc and c-jun and that some of the Cd-transformed cells may possess neoplastic potential resulting from genomic instability. (cdc.gov)
  • The poor prognosis associated with HER2 amplification may be attributed to global genomic instability as cells with high frequencies of chromosomal alterations have been associated with increased cellular proliferation and aggressive behavior. (biomedcentral.com)
  • Thus, we propose that ectopic expression of GLI2 profoundly affects the genomic integrity of human epithelial cells and contributes to the survival of progenies with genomic alterations by deregulating cell cycle proteins and disabling the apoptotic mechanisms responsible for their elimination. (qmul.ac.uk)
  • A complex story is now emerging in which MMPs not only compromise cell-cell and cell-substratum adhesion processes that impact genomic surveillance mechanisms but also act directly on molecules at the cell surface to stimulate physiological processes that cause genetic alterations. (elsevier.com)
  • Here we show that overexpression of the oncogenic kinase Pim-1 in human prostate epithelial cells induces genomic instability by subverting the mitotic spindle checkpoint. (uab.edu)
  • Data obtained will give a better understanding of the mechanisms of genomic instability and the impact of environmental agents on these mechanisms. (grantome.com)
  • Mitochondrial genomic integrity was substantially compromised in ntg1Δ pif1Δ sod2Δ strains, since these cells exhibit a total loss of mtDNA. (asm.org)
  • Various defense mechanisms operate in mitochondria to minimize the deleterious effects of oxidative stress and maintain mitochondrial genomic integrity. (asm.org)
  • Recent studies provide evidence for a role of the BRCA2 protein in the maintenance of genomic integrity by involvement in DNA repair and recombination. (springer.com)
  • The ability to repair DNA damage and maintain genomic integrity is fundamental to survival of both bacterial and fungal pathogens. (prolekare.cz)
  • My goal is to determine the possible causes of loss of genomic integrity during replicative aging in budding yeast to gain potential insight into this vastly complex process. (tmc.edu)
  • These events, in turn, influence the global genomic integrity in replicatively aged cells. (tmc.edu)
  • Model of DNA damage sensitivity as a function of genomic instability. (aacrjournals.org)
  • These results provide direct evidence that oxidative mtDNA damage can be a major contributor to mitochondrial genomic instability and demonstrate cooperation of Ntg1p and Pif1p to resist the introduction of lesions into the mitochondrial genome. (asm.org)
  • Graduate student Melina Butuci and Matthew Michael, professor of biological sciences, study genome instability in primordial germ cells using special fluorescent dyes to help them visualize damage to DNA. (usc.edu)
  • This rapid transition, called zygotic genome activation, or ZGA, is necessary for the cell's survival, but it paradoxically leads to a great deal of instability and potentially life-threatening damage to the cells' DNA. (usc.edu)
  • Sublethal antimicrobial exposure can trigger DNA damage and genomic instability across the diversity of microbial pathogens, including bacterial and fungal species. (prolekare.cz)
  • Generally, the purpose of this study is to investigate the balance between formation of genomic damage and induction of apoptosis under genotoxic stress. (uni-wuerzburg.de)
  • subsequently, after ROS clearance, the accumulated DNA damage and robust activation of DNA-PK induce genomic instability, facilitated by Rad50-mediated cell-cycle arrest, leading to enhanced malignancy, CSC overgrowth, and radioresistance. (jci.org)
  • miR-18a reactivated EBV through inhibiting the ATM-mediated DNA damage response (DDR) and caused genomic instability. (biomedcentral.com)
  • We propose that the limiting levels of repair factors and cohesin proteins impair the ability of the aged cells to counteract the increased burden of genomic damage accumulation coupled with chromosomal rearrangements and potentially chromosome loss, eventually to cross a threshold of genomic damage that is sensed by the cell to cause cessation of cell division marking the end of the replicative lifespan. (tmc.edu)
  • Overexpression of GLI2ΔN also rendered human keratinocytes resistant to UVB-mediated apoptosis, whereas inhibition of B-cell lymphoma 2 (BCL-2) restored endogenous (genomic instability (GIN)) and exogenous (UVB) DNA damage-induced apoptosis. (qmul.ac.uk)
  • The ROS stimulate the expression of the transcription factor Snail and EMT, and cause oxidative damage to DNA and genomic instability. (researchwithnj.com)
  • The aberrant upregulation of FOXM1 serves as a 'first hit' where cells acquire genomic instability which in turn predisposes cells to a 'second hit' whereby DNA-damage checkpoint response (eg. (qmul.ac.uk)
  • The overall goal of this project is to determine if low doses (below or equal to the level traditionally requiring human radiation protection, i.e. less than or equal to 10 cGy) of low LET radiation can induce genomic instability. (unt.edu)
  • Using a high-resolution Affymetrix genome-wide single nucleotide polymorphism (SNP) mapping technique, we provided the evidence that FOXM1 upregulation in epidermal keratinocytes is sufficient to induce genomic instability, in the form of loss of heterozygosity (LOH) and copy number variations (CNV). (qmul.ac.uk)
  • Repair-deficient mutants exposed to oxidative stress conditions exhibited profound genomic instability. (asm.org)
  • This present blog entry takes a different approach, relating 1 ) the "master" pathway network of inflammation (NF-kB) to two other pathway networks clearly implicated in aging and disease processes 2) Genomic Instability (p53), and 3) Oxidative stress (Nrf2). (anti-agingfirewalls.com)
  • Induction of genomic instability, oxidative processes, and mitochondrial activity by 50Hz magnetic fields in human SH-SY5Y neuroblastoma cells. (emf-portal.org)
  • The data indicate that exposure to a 50 Hz - magnetic field could disturb the oxidative / antioxidative balance immediately after the exposure and indicate an induction of genomic instability in the progeny of exposed cells . (emf-portal.org)
  • Genomic DNA was extracted from blood samples and epithelial biopsies. (nepjol.info)
  • We previously reported that high SEPT9-i1 expression in human mammary epithelial cell lines (HMECs) led to malignant cellular phenotypes such as increased cell proliferation, invasiveness, motility, and genomic instability. (elsevier.com)
  • WEE1 murine deficiency induces hyper-activation of APC/C and results in genomic instability and carcinogenesis. (sigmaaldrich.com)
  • In addition, TERRA knockdown induces telomere dysfunction and instability. (bu.edu)
  • However, p53 null cells still retain some function of certain checkpoint and repair processes, reducing the genomic changes that otherwise would occur if these mechanisms were absent. (nih.gov)
  • Accumulating evidence suggests that mutant forms of p53 proteins may drastically perturb these residual genome-stabilizing mechanisms through gain-of-function interactions with multiple proteins leading to a higher level of genomic instability than in p53 null cells. (nih.gov)
  • MYC also induced genomic destabilization in normal human fibroblasts, although these cells did not become tumorigenic. (pnas.org)
  • Proto-oncogene activation and genomic instability of cadmium-induced cell transformation in BALB/c-3T3 cells. (cdc.gov)
  • When expressed in cells, G199S induces genomic instability and cellular transformation. (sigmaaldrich.com)
  • The frequency and the type of metaphase chromosome aberrations in bone marrow cells collected from exposed mice at different times following irradiation were used as markers for radiation-induced genomic instability. (unt.edu)
  • AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation. (selleckchem.com)
  • Further, cells lacking SETD2 took longer to complete mitosis, often failed to undergo cytokinesis, and exhibited increased polyploidy, indicating an increase in genomic instability. (aacrjournals.org)
  • 6) Quantify the low dose response and the targets involved in the genomic instability phenotype in cells exposed to low LET radiation and the relationship with the bystander response. (unt.edu)
  • Despite the seemingly life-threatening genomic instability arising during embryonic development, the cells survive. (usc.edu)
  • Multifaceted phenotypic and genomic analyses of p21-inducible, p53-null, cancerous and near-normal cellular models showed that after an initial senescence-like phase, a subpopulation of p21-expressing proliferating cells emerged, featuring increased genomic instability, aggressiveness and chemoresistance. (uzh.ch)
  • In my work presented here, I uncovered a global loss of cohesion in mitotically aged yeast cells and this most likely serves as the cause of increased rDNA instability and/or ERC accumulation as observed during aging. (tmc.edu)
  • Genomic instability in its broadest sense is a feature of virtually all neoplastic cells. (ox.ac.uk)
  • Here we explored how cells process methylated RIND-EDSBs and if RIND-EDSBs play a role in global hypomethylation-induced genomic instability. (biomedcentral.com)
  • Conclusion We hypothesise that prolonged and repeated UVB exposure selects for skin cells bearing stable FOXM1 protein causes aberrant cell cycle checkpoint thereby allowing ectopic cell cycle entry and subsequent genomic instability. (qmul.ac.uk)
  • Several lines of evidence suggest that, within a lineage, particular genomic regions are subject to instability that can lead to specific types of chromosome rearrangements important in species incompatibility. (genetics.org)
  • We propose that centromeres are the primary target for destabilization in cases of genomic instability, such as interspecific hybridization, and participate in the formation of novel chromosome rearrangements. (genetics.org)
  • This instability included amplification of a satellite repeat and a transposable element, changes in chromatin structure, and de novo whole-arm rearrangements. (genetics.org)
  • These data suggest that "hot spots" in the genome are predisposed to instability and may be subject to genomic rearrangements. (genetics.org)
  • Fifty-five WDLS and 52 DDLS were analyzed using Agilent 244K comparative genomic hybridization and Affymetrix U133A expression arrays. (aacrjournals.org)
  • All samples were subjected to comparative genomic hybridization and gene expression profiling. (youscribe.com)
  • Results Comparative genomic hybridization revealed ploidy-associated specific, recurrent genomic imbalances. (youscribe.com)
  • Here, we report a novel defect of the ATM-dependent cell cycle checkpoint in melanoma cell lines that promotes genomic instability. (garvan.org.au)
  • The subtypes varied with respect to level of genomic instability. (nyu.edu)
  • The weekly Genome Instability Group meeting, supported by the Department and DLDCCC, includes 25 labs from throughout the Texas Medical Center discussing work in progress. (sciencecareers.org)
  • In summary, the goals are to take the risks of genomic instability (poor prognosis, rapid development of resistance) and turn genomic instability into an advantage for therapeutic targeting, thereby improving the prognosis for high-risk breast cancers. (mskcc.org)
  • In DDLS, loss of 11q23-24 is associated with genomic complexity and distinct morphology whereas loss of 19q13 predicts poor prognosis. (aacrjournals.org)
  • Global hypomethylation and genomic instability are cardinal features of cancers. (biomedcentral.com)
  • Each of these pathways can lead to the loss of genetic information (genomic instability). (asm.org)
  • In the report will be paying attention to 3 aspects of human life in context of emotional stress expression and its connection with genomic instability: envi-ronmental pollution, genomic predisposes, ethic and social-economic problems. (scirp.org)
  • The report will contain data from literature and results of own research directed to the analyzing the impact of the degree of emotional stress expression on the children's and adults' genomic instability. (scirp.org)
  • Conclusions We conclude that the grade of genomic instability rather than the histopathological subtype correlates with specific gene and protein expression changes. (youscribe.com)
  • Although for clinical purposes, breast cancers are categorized based on the expression of a few key markers, such as the estrogen receptor (ER), the progesterone receptor (PR) and the human epidermal growth factor receptor 2 (HER2) whose levels are assessed using immunohistochemistry (IHC)-based methods [ 1 ], recent genomic studies have uncovered much greater heterogeneity in breast cancers. (biomedcentral.com)
  • Recent data from our groups and others support two main notions, that these damaged clusters are: (1) repair resistant, increasing genomic instability (GI) and malignant transformation and (2) can be considered as persistent "danger" signals promoting chronic inflammation and immune response, causing detrimental effects to the organism (like radiation toxicity). (mdpi.com)
  • Now researchers at Baylor College of Medicine who study families with such genomic disorders have found a shared, yet unusual, architecture resulting from this jumble that is associated with very severe forms of disease. (healthcanal.com)
  • A germline polymorphism of thymine DNA glycosylase induces genomic instability and cellular transformation. (sigmaaldrich.com)
  • Here, we reveal that glioma CSCs are hypersensitive to radiation, but a temporal DNA repair mechanism converts the intrinsic sensitivity to genomic instability and treatment resistance. (jci.org)
  • Genomic instability and the role of radiation quality. (ox.ac.uk)