M Phase Cell Cycle Checkpoints: The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.G2 Phase Cell Cycle Checkpoints: CELL CYCLE regulatory signaling systems that are triggered by DNA DAMAGE or lack of nutrients during G2 PHASE. When triggered they restrain cells transitioning from G2 phase to M PHASE.Cell Cycle: The complex series of phenomena, occurring between the end of one CELL DIVISION and the end of the next, by which cellular material is duplicated and then divided between two daughter cells. The cell cycle includes INTERPHASE, which includes G0 PHASE; G1 PHASE; S PHASE; and G2 PHASE, and CELL DIVISION PHASE.G2 Phase: The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.S Phase Cell Cycle Checkpoints: Cell regulatory signaling system that controls progression through S PHASE and stabilizes the replication forks during conditions that could affect the fidelity of DNA REPLICATION, such as DNA DAMAGE or depletion of nucleotide pools.G1 Phase Cell Cycle Checkpoints: Regulatory signaling systems that control the progression of the CELL CYCLE through the G1 PHASE and allow transition to S PHASE when the cells are ready to undergo DNA REPLICATION. DNA DAMAGE, or the deficiencies in specific cellular components or nutrients may cause the cells to halt before progressing through G1 phase.Allyl CompoundsCell Cycle Proteins: Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.Cell Cycle Checkpoints: Regulatory signaling systems that control the progression through the CELL CYCLE. They ensure that the cell has completed, in the correct order and without mistakes, all the processes required to replicate the GENOME and CYTOPLASM, and divide them equally between two daughter cells. If cells sense they have not completed these processes or that the environment does not have the nutrients and growth hormones in place to proceed, then the cells are restrained (or "arrested") until the processes are completed and growth conditions are suitable.Isothiocyanates: Organic compounds with the general formula R-NCS.Mitosis: A type of CELL NUCLEUS division by means of which the two daughter nuclei normally receive identical complements of the number of CHROMOSOMES of the somatic cells of the species.DNA Damage: Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.S Phase: Phase of the CELL CYCLE following G1 and preceding G2 when the entire DNA content of the nucleus is replicated. It is achieved by bidirectional replication at multiple sites along each chromosome.Checkpoint Kinase 2: Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. The gene is located on the long (q) arm of chromosome 22 at position 12.1. In humans it is encoded by the CHEK2 gene.Cell Line, Tumor: A cell line derived from cultured tumor cells.G1 Phase: The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors.Apoptosis: One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.Genes, cdc: Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Ataxia Telangiectasia Mutated Proteins: A group of PROTEIN-SERINE-THREONINE KINASES which activate critical signaling cascades in double strand breaks, APOPTOSIS, and GENOTOXIC STRESS such as ionizing ultraviolet A light, thereby acting as a DNA damage sensor. These proteins play a role in a wide range of signaling mechanisms in cell cycle control.Protein-Serine-Threonine Kinases: A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Tumor Suppressor Protein p53: Nuclear phosphoprotein encoded by the p53 gene (GENES, P53) whose normal function is to control CELL PROLIFERATION and APOPTOSIS. A mutant or absent p53 protein has been found in LEUKEMIA; OSTEOSARCOMA; LUNG CANCER; and COLORECTAL CANCER.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.cdc25 Phosphatases: A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.CDC2 Protein Kinase: Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.Cyclin-Dependent Kinase Inhibitor p21: A cyclin-dependent kinase inhibitor that mediates TUMOR SUPPRESSOR PROTEIN P53-dependent CELL CYCLE arrest. p21 interacts with a range of CYCLIN-DEPENDENT KINASES and associates with PROLIFERATING CELL NUCLEAR ANTIGEN and CASPASE 3.DNA Repair: The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.Cyclins: A large family of regulatory proteins that function as accessory subunits to a variety of CYCLIN-DEPENDENT KINASES. They generally function as ENZYME ACTIVATORS that drive the CELL CYCLE through transitions between phases. A subset of cyclins may also function as transcriptional regulators.Cyclin B1: A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.Tumor Suppressor Proteins: Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.DNA Replication: The process by which a DNA molecule is duplicated.Cyclin B: A cyclin subtype that is transported into the CELL NUCLEUS at the end of the G2 PHASE. It stimulates the G2/M phase transition by activating CDC2 PROTEIN KINASE.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Gamma Rays: Penetrating, high-energy electromagnetic radiation emitted from atomic nuclei during NUCLEAR DECAY. The range of wavelengths of emitted radiation is between 0.1 - 100 pm which overlaps the shorter, more energetic hard X-RAYS wavelengths. The distinction between gamma rays and X-rays is based on their radiation source.Hydroxyurea: An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.Ataxia Telangiectasia: An autosomal recessive inherited disorder characterized by choreoathetosis beginning in childhood, progressive CEREBELLAR ATAXIA; TELANGIECTASIS of CONJUNCTIVA and SKIN; DYSARTHRIA; B- and T-cell immunodeficiency, and RADIOSENSITIVITY to IONIZING RADIATION. Affected individuals are prone to recurrent sinobronchopulmonary infections, lymphoreticular neoplasms, and other malignancies. Serum ALPHA-FETOPROTEINS are usually elevated. (Menkes, Textbook of Child Neurology, 5th ed, p688) The gene for this disorder (ATM) encodes a cell cycle checkpoint protein kinase and has been mapped to chromosome 11 (11q22-q23).Radiation, Ionizing: ELECTROMAGNETIC RADIATION or particle radiation (high energy ELEMENTARY PARTICLES) capable of directly or indirectly producing IONS in its passage through matter. The wavelengths of ionizing electromagnetic radiation are equal to or smaller than those of short (far) ultraviolet radiation and include gamma and X-rays.Spindle Apparatus: 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.Retinoblastoma Protein: Product of the retinoblastoma tumor suppressor gene. It is a nuclear phosphoprotein hypothesized to normally act as an inhibitor of cell proliferation. Rb protein is absent in retinoblastoma cell lines. It also has been shown to form complexes with the adenovirus E1A protein, the SV40 T antigen, and the human papilloma virus E7 protein.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.G0 Phase: A quiescent state of cells during G1 PHASE.Radiation Tolerance: The ability of some cells or tissues to survive lethal doses of IONIZING RADIATION. Tolerance depends on the species, cell type, and physical and chemical variables, including RADIATION-PROTECTIVE AGENTS and RADIATION-SENSITIZING AGENTS.Cyclin-Dependent Kinase 2: A key regulator of CELL CYCLE progression. It partners with CYCLIN E to regulate entry into S PHASE and also interacts with CYCLIN A to phosphorylate RETINOBLASTOMA PROTEIN. Its activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P27 and CYCLIN-DEPENDENT KINASE INHIBITOR P21.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cyclin-Dependent Kinases: Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Cyclin-Dependent Kinase Inhibitor p27: A cyclin-dependent kinase inhibitor that coordinates the activation of CYCLIN and CYCLIN-DEPENDENT KINASES during the CELL CYCLE. It interacts with active CYCLIN D complexed to CYCLIN-DEPENDENT KINASE 4 in proliferating cells, while in arrested cells it binds and inhibits CYCLIN E complexed to CYCLIN-DEPENDENT KINASE 2.Nocodazole: Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.Cyclin E: A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.Cyclin D1: Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.Saccharomyces cerevisiae Proteins: 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.Genomic Instability: An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.Ultraviolet Rays: That portion of the electromagnetic spectrum immediately below the visible range and extending into the x-ray frequencies. The longer wavelengths (near-UV or biotic or vital rays) are necessary for the endogenous synthesis of vitamin D and are also called antirachitic rays; the shorter, ionizing wavelengths (far-UV or abiotic or extravital rays) are viricidal, bactericidal, mutagenic, and carcinogenic and are used as disinfectants.Cell Survival: The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability.Saccharomyces cerevisiae: 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.Tumor Cells, Cultured: 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.Schizosaccharomyces: A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Schizosaccharomyces pombe Proteins: Proteins obtained from the species Schizosaccharomyces pombe. 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.RNA, Small Interfering: Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.Histones: Small chromosomal proteins (approx 12-20 kD) possessing an open, unfolded structure and attached to the DNA in cell nuclei by ionic linkages. Classification into the various types (designated histone I, histone II, etc.) is based on the relative amounts of arginine and lysine in each.DNA Breaks, Double-Stranded: Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Antineoplastic Agents, Phytogenic: Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.Cyclin-Dependent Kinase 4: Cyclin-dependent kinase 4 is a key regulator of G1 PHASE of the CELL CYCLE. It partners with CYCLIN D to phosphorylate RETINOBLASTOMA PROTEIN. CDK4 activity is inhibited by CYCLIN-DEPENDENT KINASE INHIBITOR P16.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Mimosine: 3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.Cell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Antineoplastic Agents: Substances that inhibit or prevent the proliferation of NEOPLASMS.Chromosomal Instability: An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.Interphase: The interval between two successive CELL DIVISIONS during which the CHROMOSOMES are not individually distinguishable. It is composed of the G phases (G1 PHASE; G0 PHASE; G2 PHASE) and S PHASE (when DNA replication occurs).Fungal Proteins: Proteins found in any species of fungus.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).BRCA1 Protein: The phosphoprotein encoded by the BRCA1 gene (GENE, BRCA1). In normal cells the BRCA1 protein is localized in the nucleus, whereas in the majority of breast cancer cell lines and in malignant pleural effusions from breast cancer patients, it is localized mainly in the cytoplasm. (Science 1995;270(5237):713,789-91)Cyclin A: A cyclin subtype that has specificity for CDC2 PROTEIN KINASE and CYCLIN-DEPENDENT KINASE 2. It plays a role in progression of the CELL CYCLE through G1/S and G2/M phase transitions.Aphidicolin: An antiviral antibiotic produced by Cephalosporium aphidicola and other fungi. It inhibits the growth of eukaryotic cells and certain animal viruses by selectively inhibiting the cellular replication of DNA polymerase II or the viral-induced DNA polymerases. The drug may be useful for controlling excessive cell proliferation in patients with cancer, psoriasis or other dermatitis with little or no adverse effect upon non-multiplying cells.CDC2-CDC28 Kinases: A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.Kinetochores: Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.Genes, p53: Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.Amino Acid Sequence: 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.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Gene Expression Regulation, Neoplastic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.Dose-Response Relationship, Radiation: The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.Intracellular Signaling Peptides and Proteins: Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Methyl Methanesulfonate: An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.DNA Repair Enzymes: Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.Metaphase: 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.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Chromatin: The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.Centrosome: 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).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes SMOOTH MUSCLE, stimulates CARDIAC MUSCLE, stimulates DIURESIS, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide PHOSPHODIESTERASES, antagonism of ADENOSINE RECEPTORS, and modulation of intracellular calcium handling.Nucleic Acid Synthesis Inhibitors: Compounds that inhibit cell production of DNA or RNA.RNA Interference: A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.Bromodeoxyuridine: A nucleoside that substitutes for thymidine in DNA and thus acts as an antimetabolite. It causes breaks in chromosomes and has been proposed as an antiviral and antineoplastic agent. It has been given orphan drug status for use in the treatment of primary brain tumors.Polyploidy: The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Proliferating Cell Nuclear Antigen: Nuclear antigen with a role in DNA synthesis, DNA repair, and cell cycle progression. PCNA is required for the coordinated synthesis of both leading and lagging strands at the replication fork during DNA replication. PCNA expression correlates with the proliferation activity of several malignant and non-malignant cell types.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.HCT116 Cells: Human COLORECTAL CARCINOMA cell line.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Thioguanine: An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Blastula: An early non-mammalian embryo that follows the MORULA stage. A blastula resembles a hollow ball with the layer of cells surrounding a fluid-filled cavity (blastocele). The layer of cells is called BLASTODERM.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.RNA, Messenger: 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.14-3-3 Proteins: A large family of signal-transducing adaptor proteins present in wide variety of eukaryotes. They are PHOSPHOSERINE and PHOSPHOTHREONINE binding proteins involved in important cellular processes including SIGNAL TRANSDUCTION; CELL CYCLE control; APOPTOSIS; and cellular stress responses. 14-3-3 proteins function by interacting with other signal-transducing proteins and effecting changes in their enzymatic activity and subcellular localization. The name 14-3-3 derives from numerical designations used in the original fractionation patterns of the proteins.Cdc20 Proteins: Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Gene Expression Regulation: 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.Chromosomes: 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)Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Chromosomal Proteins, Non-Histone: Nucleoproteins, which in contrast to HISTONES, are acid insoluble. They are involved in chromosomal functions; e.g. they bind selectively to DNA, stimulate transcription resulting in tissue-specific RNA synthesis and undergo specific changes in response to various hormones or phytomitogens.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.Exonucleases: Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains.Chromosome Breakage: A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.Radiation-Sensitizing Agents: Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.DNA, Fungal: Deoxyribonucleic acid that makes up the genetic material of fungi.Neoplasms: 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.Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS.Telomere: A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.Neoplasm Proteins: Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.Mutagens: 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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Chromosome Segregation: The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.Gene Deletion: A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Down-Regulation: A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Cell Line, Transformed: Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.Ubiquitin-Protein Ligase Complexes: Complexes of enzymes that catalyze the covalent attachment of UBIQUITIN to other proteins by forming a peptide bond between the C-terminal GLYCINE of UBIQUITIN and the alpha-amino groups of LYSINE residues in the protein. The complexes play an important role in mediating the selective-degradation of short-lived and abnormal proteins. The complex of enzymes can be broken down into three components that involve activation of ubiquitin (UBIQUITIN-ACTIVATING ENZYMES), conjugation of ubiquitin to the ligase complex (UBIQUITIN-CONJUGATING ENZYMES), and ligation of ubiquitin to the substrate protein (UBIQUITIN-PROTEIN LIGASES).Anaphase-Promoting Complex-Cyclosome: An E3 ubiquitin ligase primarily involved in regulation of the metaphase-to-anaphase transition during MITOSIS through ubiquitination of specific CELL CYCLE PROTEINS. Enzyme activity is tightly regulated through subunits and cofactors, which modulate activation, inhibition, and substrate specificity. The anaphase-promoting complex, or APC-C, is also involved in tissue differentiation in the PLACENTA, CRYSTALLINE LENS, and SKELETAL MUSCLE, and in regulation of postmitotic NEURONAL PLASTICITY and excitability.Anaphase: The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.Phosphoprotein Phosphatases: A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)Immunoblotting: Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Replication Protein A: A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.Genes, Fungal: The functional hereditary units of FUNGI.1-Naphthylamine: A suspected industrial carcinogen (and listed as such by OSHA). Its N-hydroxy metabolite is strongly carcinogenic and mutagenic.Topoisomerase I Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE I.Menstrual Cycle: The period from onset of one menstrual bleeding (MENSTRUATION) to the next in an ovulating woman or female primate. The menstrual cycle is regulated by endocrine interactions of the HYPOTHALAMUS; the PITUITARY GLAND; the ovaries; and the genital tract. The menstrual cycle is divided by OVULATION into two phases. Based on the endocrine status of the OVARY, there is a FOLLICULAR PHASE and a LUTEAL PHASE. Based on the response in the ENDOMETRIUM, the menstrual cycle is divided into a proliferative and a secretory phase.X-Rays: Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard X-rays are the higher energy, shorter wavelength X-rays. Soft x-rays or Grenz rays are less energetic and longer in wavelength. The short wavelength end of the X-ray spectrum overlaps the GAMMA RAYS wavelength range. The distinction between gamma rays and X-rays is based on their radiation source.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Poly(ADP-ribose) Polymerases: Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.Chromosome Aberrations: Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.bcl-2-Associated X Protein: A member of the Bcl-2 protein family and homologous partner of C-BCL-2 PROTO-ONCOGENE PROTEIN. It regulates the release of CYTOCHROME C and APOPTOSIS INDUCING FACTOR from the MITOCHONDRIA. Several isoforms of BCL2-associated X protein occur due to ALTERNATIVE SPLICING of the mRNA for this protein.DNA-Activated Protein Kinase: A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.Cyclin-Dependent Kinase Inhibitor p16: A product of the p16 tumor suppressor gene (GENES, P16). It is also called INK4 or INK4A because it is the prototype member of the INK4 CYCLIN-DEPENDENT KINASE INHIBITORS. This protein is produced from the alpha mRNA transcript of the p16 gene. The other gene product, produced from the alternatively spliced beta transcript, is TUMOR SUPPRESSOR PROTEIN P14ARF. Both p16 gene products have tumor suppressor functions.Kinetics: The rate dynamics in chemical or physical systems.Staurosporine: An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)Aurora Kinases: 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.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Exodeoxyribonucleases: 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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Rad51 Recombinase: A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.Infrared Rays: That portion of the electromagnetic spectrum usually sensed as heat. Infrared wavelengths are longer than those of visible light, extending into the microwave frequencies. They are used therapeutically as heat, and also to warm food in restaurants.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.DNA Primers: 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.Ploidies: The degree of replication of the chromosome set in the karyotype.Proteins: Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.Gene Knockdown Techniques: The artificial induction of GENE SILENCING by the use of RNA INTERFERENCE to reduce the expression of a specific gene. It includes the use of DOUBLE-STRANDED RNA, such as SMALL INTERFERING RNA and RNA containing HAIRPIN LOOP SEQUENCE, and ANTI-SENSE OLIGONUCLEOTIDES.DNA, Neoplasm: DNA present in neoplastic tissue.Cell Transformation, Neoplastic: 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.Colonic Neoplasms: Tumors or cancer of the COLON.Proto-Oncogene Proteins c-mdm2: An E3 UBIQUITIN LIGASE that interacts with and inhibits TUMOR SUPPRESSOR PROTEIN P53. Its ability to ubiquitinate p53 is regulated by TUMOR SUPPRESSOR PROTEIN P14ARF.Breast Neoplasms: Tumors or cancer of the human BREAST.Gene Silencing: Interruption or suppression of the expression of a gene at transcriptional or translational levels.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Camptothecin: An alkaloid isolated from the stem wood of the Chinese tree, Camptotheca acuminata. This compound selectively inhibits the nuclear enzyme DNA TOPOISOMERASES, TYPE I. Several semisynthetic analogs of camptothecin have demonstrated antitumor activity.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Cell Aging: The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Meiosis: A type of CELL NUCLEUS division, occurring during maturation of the GERM CELLS. Two successive cell nucleus divisions following a single chromosome duplication (S PHASE) result in daughter cells with half the number of CHROMOSOMES as the parent cells.Protein-Tyrosine Kinases: Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.Protein Kinase Inhibitors: Agents that inhibit PROTEIN KINASES.DNA Helicases: 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.Cytoplasm: The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)Base Pair Mismatch: The presence of an uncomplimentary base in double-stranded DNA caused by spontaneous deamination of cytosine or adenine, mismatching during homologous recombination, or errors in DNA replication. Multiple, sequential base pair mismatches lead to formation of heteroduplex DNA; (NUCLEIC ACID HETERODUPLEXES).Endonucleases: Enzymes that catalyze the hydrolysis of the internal bonds and thereby the formation of polynucleotides or oligonucleotides from ribo- or deoxyribonucleotide chains. EC 3.1.-.Proto-Oncogene Proteins c-myc: 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.Immunoprecipitation: The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.Microtubule-Associated Proteins: High molecular weight proteins found in the MICROTUBULES of the cytoskeletal system. Under certain conditions they are required for TUBULIN assembly into the microtubules and stabilize the assembled microtubules.Two-Hybrid System Techniques: Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Fluorescent Antibody Technique: Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.E2F Transcription Factors: A family of basic helix-loop-helix transcription factors that control expression of a variety of GENES involved in CELL CYCLE regulation. E2F transcription factors typically form heterodimeric complexes with TRANSCRIPTION FACTOR DP1 or transcription factor DP2, and they have N-terminal DNA binding and dimerization domains. E2F transcription factors can act as mediators of transcriptional repression or transcriptional activation.PhosphoproteinsAdaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesCDC28 Protein Kinase, S cerevisiae: A protein kinase encoded by the Saccharomyces cerevisiae CDC28 gene and required for progression from the G1 PHASE to the S PHASE in the CELL CYCLE.Methylnitronitrosoguanidine: A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Recombinant Proteins: Proteins prepared by recombinant DNA technology.

*  MDC1 regulates intra-S-phase checkpoint by targeting NBS1 to DNA double-strand breaks | PNAS
Functionally, the MDC1-NBS1 interaction is required for the intra-S-phase cell cycle checkpoint control after DNA damage. ... Cells derived from NBS and ATLD patients are hypersensitive to radiation and display impaired intra-S-phase checkpoint ... It seems that phosphorylation of MDC1 at different segments regulates the assembly of distinct subsets of cell cycle checkpoint ... The evolutionarily conserved MRE11/RAD50/NBS1 (MRN) complex plays important roles in cell cycle checkpoint signaling and DNA ...
  http://www.pnas.org/content/105/32/11200
*  Pharmacological inhibition of autophagy leads to a casp | Open-i
Jurkat T cells overexpressing ATG5 or control cells were cul ... inhibition of autophagy leads to a caspase-dependent cell death ... Jurkat Cells. *M Phase Cell Cycle Checkpoints/drug effects/genetics. *RNA Interference ... b) Cell cycle analysis. Normal Jurkat T cells and cells overexpressing ATG5 were cultured for 48 h in the presence and absence ... b) Cell cycle analysis. Normal Jurkat T cells and cells overexpressing ATG5 were cultured for 48 h in the presence and absence ...
  https://openi.nlm.nih.gov/detailedresult.php?img=PMC3753548_ncomms3130-f6&req=4
*  Radiosensitizer - Wikipedia
... fluoropyrimidines increase sensitivity by dysregulating S-phase cell cycle checkpoints in tumor cells. Gemcitabine progresses ... causing cells in the S-phase to disrepair DNA damage caused by the radiation. Platinum analogs such as cisplatin inhibit DNA ... Tumor cells in a hypoxic environment may be as much as 2 to 3 times more resistant to radiation damage than those in a normal ... A radiosensitizer is an agent that makes tumor cells more sensitive to radiation therapy. It is sometimes also known as a ...
  https://en.wikipedia.org/wiki/Radiosensitizer
*  JoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols
This signal is crucial to activate the S phase checkpoint, which promotes cell cycle delay. We report here that a pol30-K107 ... phosphorylated and activated Chk1 leads to many downstream effects in the DNA damage checkpoint including cell cycle arrest, ... CD4 T cells, in vitro differentiation, regulatory T cell, virus, cell, flow cytometry ... Xenopus laevis egg extracts are emerging as a powerful cell-free extract model system in DNA damage checkpoint research. Low- ...
  https://www.jove.com/visualize/abstract/23824283/unligated-okazaki-fragments-induce-pcna-ubiquitination-requirement
*  Plus it
Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of Cdc25C. J Biol Chem ... degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle ... Cell cycle arrest, apoptosis induction, and inhibition of nuclear factor κB activation in anti-proliferative activity of benzyl ... Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J Biol Chem 2005; 280: ...
  http://cancerres.aacrjournals.org/content/67/5/2239
*  "Regulation of Zygotic Transcription and Cell Cycle Checkpoints in Earl" by Xiang Maomao Zhang
Cell proliferation occurs rapidly because cleavage cycles lack the gap phases and cell cycle checkpoints found in canonical ... which initiates extensive cell cycle remodeling. Cell cycles lengthen, gap phases appear and checkpoint function is acquired. ... Further, the genetic materials required to sustain cleavage cycles are preloaded during oogenesis, aiding efficient cell cycle ... I show that SAC acquisition is independent of the N:C ratio and other MBT events like cell cycle elongation and zygotic ...
  https://repository.upenn.edu/edissertations/1521/
*  2012 Oncomine Citations | Thermo Fisher Scientific - CN
Loss of CCDC6 affects cell cycle through impaired intra-S-phase checkpoint control.. Thanasopoulou A, Stravopodis DJ, Dimas KS ... Cell Cycle. 2012 Nov 1;11(21):4093-5. , Pubmed. *High bone sialoprotein (BSP) expression correlates with increased tumor grade ... J Cell Physiol. 2012 May 2. , Pubmed. *Identification of PBX1 Target Genes in Cancer Cells by Global Mapping of PBX1 Binding ... Mol Cell Biochem. 2012 Jan 5. , Pubmed. *Integrated genomic analyses identify WEE1 as a critical mediator of cell fate and a ...
  https://www.thermofisher.com/cn/zh/home/life-science/cancer-research/cancer-genomics/cancer-genomics-data-analysis-compendia-bioscience/oncomine-cancer-genomics-data-analysis-library/oncomine-platform-citations/2012-oncomine-citations.html
*  UV Signal Transduction for Countering Deleterious Effects of UV Radiation in Plant | Springer for Research & Development
Culligan K, Tissier A, Britt A (2004) ATR regulates a G2-phase cell-cycle checkpoint in Arabidopsis thaliana. Plant Cell 16(5): ... In this signaling process, damaged DNA-induced cell cycle arrest allows time for DNA repair. UVR8 on perception of low-dose UV ... flavonoids that, on accumulation (ununiformly) along inner surface of mesophyll cell, restrain (partially) UV entry into cells ... Annu Rev Cell Dev Biol 15:33-62PubMedCrossRefGoogle Scholar ... Thus through cell signaling mechanisms plants acclimatize to UV ...
  https://rd.springer.com/chapter/10.1007/978-81-322-2767-0_5
*  Plus it
Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase. J Biol Chem 2004; 279: 16433-40. ... When a double-strand break (DSB) occurs, the cell activates its checkpoint machinery to halt cell cycle progression and allow ... cells with ≥5 foci per cell. B, RPA70 RNAi plasmid was cotransfected into HeLa cells along with an EGFP vector. The cells were ... Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G(1)/S checkpoint activation ...
  http://cancerres.aacrjournals.org/content/65/4/1158
*  Material Search Results
This is an interactive tool in which students can explore the phases of the eukaryotic cell cycle, the checkpoints that... see ... Plant Life Cycles, Photosynthesis,... Plant Life Cycles, Photosynthesis, and Other Learning Objects ... Plant Life Cycles, Photosynthesis, and Other Learning Objects This is a great site from the University of Alberta that provides ...
  https://www.merlot.org/merlot/materials.htm?nosearchlanguage=&pageSize=&page=6&nosearchlanguage=&category=2608&sort.property=dateCreated
*  What Makes a Cancer Cell a Cancer Cell? - Holland-Frei Cancer Medicine - NCBI Bookshelf
Studies of cell transformation in vitro, however, have many pitfalls. These ... Treatment of animals or cells in culture with carcinogenic agents is a means of studying discrete biochemical events that lead ... Cancer cells, on the other hand, can continue through these checkpoints into cell-cycle phases that make them more susceptible ... Cell-Cycle Regulation. Cell-cycle checkpoints occur at key transitions in the cell cycle and provide go/no go decision points ...
  https://www.ncbi.nlm.nih.gov/books/NBK12516/
*  JoVE | Peer Reviewed Scientific Video Journal - Methods and Protocols
DNA repair and G2-phase cell cycle checkpoint responses are involved in the manifestation of hyper-radiosensitivity (HRS). The ... Defects in cell cycle checkpoint activation and the DNA damage response in irradiated cells (0.2 Gy) were evaluated. HRS was ... expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. ... Remarkably, whereas iNKT cell subsets could induce CD40 and CD86 expression by B cells, iNKT cell-matured B cells were unable ...
  https://www.jove.com/visualize?author=Ann%20Atzberger%20
*  CHK - Kinases (Serine-Threonine Specific Protein) - Transferases - Enzymes - Products
CHK1 is a checkpoint kinase in mammals and regulates G2-M and S-phase cell-cycle checkpoints. It is expressed in the S and G2 ... and checkpoint kinase 2 (CHK2), have emerged as the major mediators of cell cycle checkpoints in response to genotoxic stress[1 ... checkpoint kinase 2, and mitogen-activated protein kinase-activated protein kinase 2 in mediatingDNA damage-induced cell cycle ... In normal cells, checkpoint responses are a critical safeguard to prevent tumorigenesis promoted by genetic instability. Two ...
  https://www.axonmedchem.com/products/enzymes/transferases/kinases-serine-threonine-specific-protein/chk
*  Cell cycle responses to low-dose ionizing radiation. | Cancer Research
Additionally, the dose response pattern for the induction of the "early" G2-phase cell cycle checkpoint in MR4 cells was ... G2-phase cell cycle delay in response to low doses (0-0.3 Gy) of irradiation although an immediate cell cycle delay was evident ... ATM-dependent G2 cell-cycle checkpoint. High-precision cell survival experiments using flow cytometry synchronized cell ... We found that the MR4 cells exhibited a pronounced HRS cell survival response that was exaggerated in a G2-phase enriched cell ...
  http://cancerres.aacrjournals.org/content/66/8_Supplement/1214.4
*  MDC1 - Wikipedia
This protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. MDC1 ... Knock out MDC1 mice cells and silenced human cells were radiosensitive, failed to initiate Intra-S phase and G2/M checkpoints, ... MDC1 protein is a regulator of the Intra-S phase and the G2/M cell cycle checkpoints and recruits repair proteins to the site ... and cell cycle alterations in NFBD1-depleted human esophageal cancer cells". Mol Cell Biochem. 342 (1-2): 1-6. doi:10.1007/ ...
  https://en.wikipedia.org/wiki/MDC1
*  IGF-1R inhibition induces schedule-dependent sensitization of human melanoma to temozolomide.
G1 Phase Cell Cycle Checkpoints. Humans. Imidazoles. Melanoma. Mice, Inbred BALB C. ... cell cycle progression and DSB induction. IGF-1Ri sensitized BRAF wild-type and mutant melanoma cells to TMZ in vitro, an ... Cells harboring wild-type p53 were more sensitive to IGF-1Ri, and showed schedule-dependent chemo-sensitization that was most ... and in MGMT-proficient cell lines, with phospho-IGF-1R (r = 0.81, p = 0.038), suggesting that TMZ resistance associates with ...
  https://pearl.plymouth.ac.uk/handle/10026.1/10343
*  Targetting Cdks in Cancer: An Overview and New Insights | OMICS International
... are the actual driving forces behind the progression of cell cycle in eukaryotic cells. The activity level of thes.. ... The cell cycle checkpoints stringently regulate each phase of cycle before the completion of whole process. Activation of these ... Regulation of cell cycle. Cell cycle is divided into four distinct phases (G1, S, G2, and M). Each phase of the cell cycle is ... Progression of cells through four sequential phases of cell cycle namely, G1, S, G2 and M phase is tightly controlled and ...
  https://www.omicsonline.org/open-access/targetting-cdks-in-cancer-an-overview-and-new-insights-1948-5956.1000313.php?aid=36618
*  Recombination Pathways Supporting the Viability of CTF4 | Open-i
G2 Phase Cell Cycle Checkpoints/genetics. *Microscopy, Electron. *Models, Genetic. *Multiprotein Complexes/genetics/metabolism ... and pri1-M4 rad51Δ cells (obtained from crossing FY1162 carrying the direct repeat construct, with ctf4Δ rad51Δ and pri1-M4 ... and pri1-M4 rad51Δ cells (obtained from crossing FY1162 carrying the direct repeat construct, with ctf4Δ rad51Δ and pri1-M4 ...
  https://openi.nlm.nih.gov/detailedresult.php?img=PMC4352764_gr5&req=4
*  MDC1 polyclonal antibody - (PAB8487) - Products - Abnova
The encoded protein is required to activate the intra-S phase and G2/M phase cell cycle checkpoints in response to DNA damage. ... MDC1 is required for the intra-S-phase DNA damage checkpoint.. Goldberg M, Stucki M, Falck J, D'Amours D, Rahman D, Pappin D, ... Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. ... Western blot analysis of extract from 293T (lane 1) and HeLa cells (lane 2) , using MDC1 polyclonal antibody (Cat # PAB8487) . ...
  http://www.abnova.com/products/products_detail.asp?catalog_id=PAB8487
*  Inhibition of LIMKs decreases Aurora A autophosphorylat | Open-i
Cell Proliferation/drug effects. *Cell Survival/drug effects. *G2 Phase Cell Cycle Checkpoints/drug effects ... but rather due to inhibition of cell cycle progression as evidenced by accumulation of cells in G2/M phase. Inhibition of LIMKs ... but rather due to inhibition of cell cycle progression as evidenced by accumulation of cells in G2/M phase. Inhibition of LIMKs ... LIMKs also translocate into the nucleus and regulate cell cycle progression. Significantly, LIMKs are overexpressed in several ...
  https://openi.nlm.nih.gov/detailedresult.php?img=PMC4016185_nihms550223f7&req=4
*  Conjugate inhibits androgen receptor transactivation an | Open-i
Conjugate inhibits androgen receptor transactivation and translocation in prostate cancer cells.Effect of conjugate on the ... G2 Phase Cell Cycle Checkpoints/drug effects. *MAP Kinase Signaling System/drug effects ... The reduced proliferation of PC-3 as well as LNCaP cells by conjugate correlated with accumulation of cells in G2/M phase and ... The reduced proliferation of PC-3 as well as LNCaP cells by conjugate correlated with accumulation of cells in G2/M phase and ...
  https://openi.nlm.nih.gov/detailedresult.php?img=PMC3974779_pone.0093335.g007&req=4
*  Expression of cell cycle regulatory factors hus1, gadd45a, rb1, cdkn2a and mre11a correlates with expression of clock gene per2...
The aim of the present study was to identify genes related to per2expression and involved in cell... ... Weiss RS, Leder P, Vaziri C (2003) Critical role for mouse Hus1 in an S-phase DNA damage cell cycle checkpoint. Mol Cell Biol ... Abraham RT (2001) Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev 15:2177-2196PubMedCrossRefGoogle ... Kastan MB, Bartek J (2004) Cell-cycle checkpoints and cancer. Nature 432:316-323PubMedCrossRefGoogle Scholar ...
  https://link.springer.com/article/10.1007%2Fs11033-013-2749-2
*  Pre-clinical evaluation of a novel class of anti-cancer agents, the Pyrrolo-1, 5-benzoxazepines
... to the G2/M phase. Each phase of the cell cycle is highly regulated by cell cycle checkpoints. Activation of such checkpoints ... Cell cycle arrest is characterised as an increase in the percentage of cells at one or more phases of the cell cycle and can be ... Modulators of the cell cycle. Rapid cell division is a common trait amongst cancer cells. The cell cycle progresses from the G1 ... Nat Rev Mol Cell Biol. 2008;9:1004-10 53. Danial NN. BCL-2 family proteins: critical checkpoints of apoptotic cell death. Clin ...
  http://www.jcancer.org/v07p2367.htm
*  The Cell Cycle Flashcards by Rose L | Brainscape
Study The Cell Cycle flashcards from Rose L ... G1: cell growth and checkpoint. S phase: DNA and chromosome ... Checkpoints are times in the cell cycle where a cell's enzyme reviews the state of the cell to determine if the cell is ... cell elongates. - contraction of PM across the middle of cell produces 2 daughter cells with new cell walls ... cell will go through check point, of there are any errors cell will either correct them or enter non dividing stage (G0) ...
  https://www.brainscape.com/flashcards/the-cell-cycle-6117036/packs/9367096
*  Targeting ATR for Cancer Therapy: Profile and Expectations for ATR Inhibitors | Springer for Research & Development
... that signals DNA damage via CHK1 phosphorylation to the S and G2/M cell cycle checkpoints and to promote DNA repair. It is ... Dart DA, Adams KE, Akerman I, Lakin ND (2004) Recruitment of the cell cycle checkpoint kinase ATR to chromatin during S-phase. ... Ataxia Telangiectasia Mutated and RAD3 related (ATR) ATR inhibitor Cell cycle checkpoint Replication stress DNA repair ... Hurley PJ, Wilsker D, Bunz F (2007) Human cancer cells require ATR for cell cycle progression following exposure to ionizing ...
  https://rd.springer.com/chapter/10.1007%2F978-3-319-75836-7_4

Sunda (asura): A mythological character from the great epic Mahabharata, Sunda (सुन्‍द) was an asura prince and the brother of Upasunda. Their father was Jambha.Start point (yeast): The Start checkpoint is a major cell cycle checkpoint in yeast. The Start checkpoint ensures irreversible cell-cycle entry even if conditions later become unfavorable.Organosulfur compounds: Organosulfur compounds are organic compounds that contain sulfur. They are often associated with foul odors, but many of the sweetest compounds known are organosulfur derivatives, e.Allyl isothiocyanateBookmarking: Bookmarking (also "gene bookmarking" or "mitotic bookmarking") refers to a potential mechanism of transmission of gene expression programs through cell division.G2-M DNA damage checkpoint: The G2-M DNA damage checkpoint is an important cell cycle checkpoint in eukaryotic organisms ranging from yeast to mammals. This checkpoint ensures that cells don't initiate mitosis before they have a chance to repair damaged DNA after replication.Serine/threonine-specific protein kinaseMinC: The MinC protein is one of three proteins encoded by the minB operon and which is required to generate pole to pole oscillations prior to bacterial cell division as a means of specifying the midzone of the cell. This function is achieved by preventing the formation of the divisome Z-ring around the poles.P53: Tumor protein p53, also known as p53, cellular tumor antigen p53 (UniProt name), phosphoprotein p53, tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53), is any isoform of a protein encoded by homologous genes in various organisms, such as TP53 (humans) and Trp53 (mice). This homolog (originally thought to be, and often spoken of as, a single protein) is crucial in multicellular organisms, where it prevents cancer formation, thus, functions as a tumor suppressor.Hyperphosphorylation: Hyperphosphorylation occurs when a biochemical with multiple phosphorylation sites is fully saturated. Hyperphosphorylation is one of the signalling mechanisms used by the cell to regulate mitosis.Kinome: In molecular biology, the kinome of an organism is the set of protein kinases in its genome. Kinases are enzymes that catalyze phosphorylation reactions (of amino acids) and fall into several groups and families, e.Base excision repair: frame|right|Basic steps of base excision repair|Basic steps of base excision repairCyclin: Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes.DNA-binding proteinFlow cytometry: In biotechnology, flow cytometry is a laser-based, biophysical technology employed in cell counting, cell sorting, biomarker detection and protein engineering, by suspending cells in a stream of fluid and passing them by an electronic detection apparatus. It allows simultaneous multiparametric analysis of the physical and chemical characteristics of up to thousands of particles per second.DNA re-replication: DNA re-replication (or simply rereplication) is an undesirable and possibly fatal occurrence in eukaryotic cells in which the genome is replicated more than once per cell cycle. Rereplication is believed to lead to genomic instability and has been implicated in the pathologies of a variety of human cancers.Clb 5,6 (Cdk1): Clb5 and Clb6 are B-type, S-phase cyclins in yeast that assist in cell cycle regulation.Morgan, DO (2007) 'The Cell Cycle: Principles of Control, Oxford University Press Clb5 and Clb6 bind and activate Cdk1, and high levels of these cyclins are required for entering S-phase.Gamma counter: A gamma counter is a machine to measure gamma radiation emitted by a radionuclide. A large number of samples are placed in sealed vials or test tubes, and move along a serpentine track on a horizontal plane.Hydroxyurea dermopathyAtaxia telangiectasia mutated: Ataxia telangiectasia mutated (ATM) is a serine/threonine protein kinase that is recruited and activated by DNA double-strand breaks. It phosphorylates several key proteins that initiate activation of the DNA damage checkpoint, leading to cell cycle arrest, DNA repair or apoptosis.Spindle apparatus: In cell biology, the spindle apparatus refers to the subcellular structure of eukaryotic cells that separates chromosomes between daughter cells during cell division. It is also referred to as the mitotic spindle during mitosis, a process that produces genetically identical daughter cells, or the meiotic spindle during meiosis, a process that produces gametes with half the number of chromosomes of the parent cell.Pocket protein family: Pocket protein family consists of three proteins:Cyclin-dependent kinase complex: A cyclin-dependent kinase complex (CDKC, cyclin-CDK) is a protein complex formed by the association of an inactive catalytic subunit of a protein kinase, cyclin-dependent kinase (CDK), with a regulatory subunit, cyclin.Malumbres M, Barbacid M.Silent mutation: Silent mutations are mutations in DNA that do not significantly alter the phenotype of the organism in which they occur. Silent mutations can occur in non-coding regions (outside of genes or within introns), or they may occur within exons.NocodazoleCyclin D/Cdk4: The Cyclin D/Cdk4 complex is a multi-protein structure consisting of the proteins Cyclin D and cyclin-dependent kinase 4, or Cdk4, a serine-threonine kinase. This complex is one of many cyclin/cyclin-dependent kinase complexes that are the "hearts of the cell-cycle control system" and govern the cell cycle and its progression.UVB-induced apoptosis: UVB-induced apoptosis is the programmed cell death of cells that become damaged by ultraviolet rays. This is notable in skin cells, to prevent melanoma.Zuotin: Z-DNA binding protein 1, also known as Zuotin, is a Saccharomyces cerevisiae yeast gene.Schizosaccharomyces pombe: Schizosaccharomyces pombe, also called "fission yeast", is a species of yeast used in traditional brewing and as a model organism in molecular and cell biology. It is a unicellular eukaryote, whose cells are rod-shaped.Dermal fibroblast: Dermal fibroblasts are cells within the dermis layer of skin which are responsible for generating connective tissue and allowing the skin to recover from injury. Using organelles (particularly the rough endoplasmic reticulum), dermal fibroblasts generate and maintain the connective tissue which unites separate cell layers.Histone octamer: A histone octamer is the eight protein complex found at the center of a nucleosome core particle. It consists of two copies of each of the four core histone proteins (H2A, H2B, H3 and H4).Coles PhillipsMimosineMatrix model: == Mathematics and physics ==Antileukemic drug: Antileukemic drugs, anticancer drugs that are used to treat one or more types of leukemia, include:DNA condensation: DNA condensation refers to the process of compacting DNA molecules in vitro or in vivo. Mechanistic details of DNA packing are essential for its functioning in the process of gene regulation in living systems.Kinetochore: The kinetochore is the protein structure on chromatids where the spindle fibers attach during cell division to pull sister chromatids apart.Protein primary structure: The primary structure of a peptide or protein is the linear sequence of its amino acid structural units, and partly comprises its overall biomolecular structure. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end.Pituitary-specific positive transcription factor 1: POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1), also known as POU1F1, is a transcription factor for growth hormone.Proximity ligation assay: Proximity ligation assay (in situ PLA) is a technology that extends the capabilities of traditional immunoassays to include direct detection of proteins, protein interactions and modifications with high specificity and sensitivity. Protein targets can be readily detected and localized with single molecule resolution and objectively quantified in unmodified cells and tissues.Hippo signaling pathway: The Hippo signaling pathway, also known as the Salvador/Warts/Hippo (SWH) pathway, controls organ size in animals through the regulation of cell proliferation and apoptosis. The pathway takes its name from one of its key signaling components—the protein kinase Hippo (Hpo).Temporal analysis of products: Temporal Analysis of Products (TAP), (TAP-2), (TAP-3) is an experimental technique for studyingAdaptive response: The adaptive response is a form of direct DNA repair in E. coli that protects DNA from damage by external agents or by errors during replication.Metaphase: Metaphase (from the Greek μετά, "adjacent" and φάσις, "stage") is a stage of mitosis in the eukaryotic cell cycle in which chromosomes are at their second-most condensed and coiled stage (they are at their most condensed in anaphase. These chromosomes, carrying genetic information, align in the equator of the cell before being separated into each of the two daughter cells.Concentration effect: In the study of inhaled anesthetics, the concentration effect is the increase in the rate that the Fa(alveolar concentration)/Fi(inspired concentration) ratio rises as the alveolar concentration of that gas is increased. In simple terms, the higher the concentration of gas administered, the faster the alveolar concentration of that gas approaches the inspired concentration.Bivalent chromatin: Bivalent chromatin are segments of DNA, bound to histone proteins, that have both repressing and activating epigenetic regulators in the same region. These regulators work to enhance or silence the expression of genes.Centrosome cycle: Centrosomes are the major microtubule organizing center (MTOC) in mammalian cells. Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy.Symmetry element: A symmetry element is a point of reference about which symmetry operations can take place. In particular, symmetry elements can be centers of inversion, axes of rotation and mirror planes.

(1/221) Spindle assembly checkpoint-related failure perturbs early embryonic divisions and reduces reproductive performance of LT/Sv mice.

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(2/221) The nucleoporin Nup153 affects spindle checkpoint activity due to an association with Mad1.

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(3/221) Unliganded progesterone receptors attenuate taxane-induced breast cancer cell death by modulating the spindle assembly checkpoint.

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(4/221) RNA binding protein CUGBP2/CELF2 mediates curcumin-induced mitotic catastrophe of pancreatic cancer cells.

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(5/221) Aneuploidy and tumorigenesis.

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(6/221) Correction of microtubule-kinetochore attachment errors: mechanisms and role in tumor suppression.

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(7/221) Mutual regulation between the spindle checkpoint and APC/C.

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(8/221) Polycomb protein EZH2 regulates cancer cell fate decision in response to DNA damage.

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  • Mammalian
  • Mammalian cells have established highly elaborate surveillance systems to detect DNA damages and other forms of genotoxic stress, which is essential to maintain the genomic integrity and, hence, cellular viability. (axonmedchem.com)
  • discovered a third DNA polymerase activity in mammalian cells that was called polymerase delta (δ). (wikipedia.org)
  • proteins
  • We noticed that in contrast to robust MDC1 foci formation after DNA damage, the formation of NBS1 foci in cells expressing exogenous NBS1 was not readily detectable ( Fig. 1 A ). We speculated that this failure of proper NBS1 localization could be due to the limited expression of an endogenous protein or proteins required for NBS1 foci formation in vivo . (pnas.org)
  • As the eukaryotic cell cycle is a complex process, eukaryotes have evolved a network of regulatory proteins, known as the cell cycle control system, which monitors and dictates the progression of the cell through the cell cycle. (wikipedia.org)
  • Upon the decision to progress past the G1 checkpoint, cyclin D levels rise, and cyclin D forms a complex with CDK4 and CDK6, which in turn phosphorylate the pocket proteins. (wikipedia.org)
  • In this phase, the cell increases its supply of proteins, increases the number of organelles (such as mitochondria, ribosomes), and grows in size. (wikipedia.org)
  • These gene regulatory proteins control G1/S genes, and their negative regulation assists in shutting off expression of G1 cyclins during S-phase. (wikipedia.org)
  • Another regulatory element, the cell cycle element/cell cycle genes homology region (CDE/CHR), located downstream of the start site is important for POLD1 transcription in G2/M phase by E2F1 and p21 proteins. (wikipedia.org)
  • Regulation of one or more proteins involved in this checkpoint is lost in many cancers. (wikipedia.org)
  • Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. (wikipedia.org)
  • Before the discovery of the ubiquitin proteasome system, protein degradation in cells was thought to rely mainly on lysosomes, membrane-bound organelles with acidic and protease-filled interiors that can degrade and then recycle exogenous proteins and aged or damaged organelles. (wikipedia.org)
  • inhibits
  • Conjugate inhibits androgen receptor transactivation and translocation in prostate cancer cells.Effect of conjugate on the transactivation of androgen receptor in presence/absence of 10 nM DHT in (A) androgen receptor positive LNCaP cells and (B) androgen receptor negative PC-3 cells. (nih.gov)
  • This protein controls cell cycle progression and proneural genes expression by acting as a transcription coregulator that enhances or inhibits the activity of transcription factors. (wikipedia.org)
  • Humans
  • Furthermore, individual cells of malignant tumors growing in animals or in humans exhibit marked biochemical heterogeneity, as reflected in their cell surface composition, enzyme levels, immunogenicity, response to anticancer drugs, and so on. (nih.gov)
  • Activation of iNKT cells can protect against multiple diseases in mice but clinical trials in humans have had limited impact. (jove.com)
  • Mediator of DNA damage checkpoint protein 1 is a 2080 amino acid long protein that in humans is encoded by the MDC1 gene located on the short arm (p) of chromosome 6. (wikipedia.org)
  • In humans, Down syndrome appears in children carrying in their cells one extra copy of chromosome 21, as a result of a defect in chromosome segregation during meiosis in one of the progenitors. (wikipedia.org)
  • M-phase inducer phosphatase 1 also known as dual specificity phosphatase Cdc25A is a protein that in humans is encoded by the cell division cycle 25 homolog A (CDC25A) gene. (wikipedia.org)
  • Protein BTG2 also known as BTG family member 2 or NGF-inducible anti-proliferative protein PC3 or NGF-inducible protein TIS21, is a protein that in humans is encoded by the BTG2 gene (B-cell translocation gene 2) and in other mammals by the homologous Btg2 gene. (wikipedia.org)
  • vitro
  • Studies of cell transformation in vitro, however, have many pitfalls. (nih.gov)
  • These "tissue-culture artifacts" include overgrowth of cells not characteristic of the original population of cultured cells (eg, overgrowth of fibroblasts in cultures that were originally primarily epithelial cells), selection for a small population of variant cells with continued passage in vitro, or appearance of cells with an abnormal chromosomal number or structure (karyotype). (nih.gov)
  • Over the past 60 years, much scientific effort has gone into research aimed at identifying the phenotypic characteristics of in vitro-transformed cells that correlate with the growth of a cancer in vivo. (nih.gov)
  • double-negative (DN) iNKT cells with autologous peripheral B cells in vitro. (jove.com)
  • IGF-1Ri sensitized BRAF wild-type and mutant melanoma cells to TMZ in vitro, an effect that was independent of MGMT. (plymouth.ac.uk)
  • chromosomes
  • During the final stage, cytokinesis, the chromosomes and cytoplasm separate into two new daughter cells. (wikipedia.org)
  • M phase is itself composed of two tightly coupled processes: karyokinesis, in which the cell's chromosomes are divided, and cytokinesis, in which the cell's cytoplasm divides forming two daughter cells. (wikipedia.org)
  • In order to preserve the cell's identity and proper function, it is necessary to maintain the appropriate number of chromosomes after each cell division. (wikipedia.org)
  • An error in generating daughter cells with fewer or greater number of chromosomes than expected (a situation termed aneuploidy), may lead in best case to cell death, or alternatively it may generate catastrophic phenotypic results. (wikipedia.org)
  • Microtubules (MTs) are long proteic filaments, with asymmetric extremities: one end termed "minus" (-) end, relatively stable and close to the centrosome, and an end termed "plus" (+) end, with alternating phases of growth and retraction, exploring the center of the cell searching the chromosomes. (wikipedia.org)
  • Accumulation
  • Disruption of the MDC1-NBS1 interaction results in failure of NBS1 accumulation at DNA double-strand breaks and impairment of intra-S checkpoint activation. (pnas.org)
  • flavonoids that, on accumulation (ununiformly) along inner surface of mesophyll cell, restrain (partially) UV entry into cells thereby conferring UV acclimation under high intensity UV radiation in plants. (springer.com)
  • Thus, the regulation of Cdc6p is tightly correlated to the activity of Cdk2 and since Cdk2-activity is oscillating once per cell cycle, the accumulation and degradation of Cdc6p also oscillates. (wikipedia.org)
  • mechanism
  • Gemcitabine progresses through a similar mechanism, causing cells in the S-phase to disrepair DNA damage caused by the radiation. (wikipedia.org)
  • While a complete understanding of the underlying molecular mechanism of this radiation response is not clear, our recent work has identified a connection between low-dose HRS survival, Ataxia Telangiectasia Mutated (ATM)-mediated repair pathways and an "early" ATM-dependent G2 cell-cycle checkpoint. (aacrjournals.org)
  • The MDC1 gene encodes the MDC1 nuclear protein which is part of the DNA damage response (DDR) pathway, the mechanism through which eukaryotic cells respond to damaged DNA, specifically DNA double-strand breaks (DSB) that are caused by ionizing radiation or chemical clastogens. (wikipedia.org)
  • Examples include: In cancer cells, aneuploidy is a frequent event, indicating that these cells present a defect in the machinery involved in chromosome segregation, as well as in the mechanism ensuring that segregation is correctly performed. (wikipedia.org)
  • The mechanism responsible for the correct distribution of sister chromatids during cell division is named chromosome segregation. (wikipedia.org)
  • To ensure that chromosome segregation takes place correctly, cells have developed a precise and complex mechanism. (wikipedia.org)
  • pathway
  • Targeting COX-2/PGE(2) pathway in HIPK2 knockdown cancer cells: impact on dendritic cell maturation. (thermofisher.com)
  • This pathway contains 2 positive feedback loops, allowing for rapid, unidirectional movement into S-phase. (wikipedia.org)
  • However, this pathway is stimulated by the upstream binding of growth factors (GF), either from within the cell itself or from neighboring cells. (wikipedia.org)
  • gene
  • Jurkat T cells either overexpressing ATG5 following lentiviral gene transfer or treated with etoposide were cultured in the presence and absence of the indicated pharmacological inhibitors for the indicated times to block autophagy and caspase activity. (nih.gov)
  • 27 Such cell lines may also be generated by transfection of the telomerase gene into cells to maintain chromosomal length. (nih.gov)
  • Recently, however, Hahn and colleagues 28 showed that ectopic expression of the human telomerase catalytic subunit (human telomerase reverse transcriptase [hTERT]) in combination with the oncogenes h- ras and SV40 virus large-T antigen can induce tumorigenic conversion in normal human epithelial and fibroblast cells, suggesting that disruption of the intracellular pathways regulated by these gene products is sufficient to produce a malignant cell. (nih.gov)
  • This is partly because the CDC6 gene is only transcribed during G1 phase. (wikipedia.org)
  • synthesis
  • The first phase within interphase, from the end of the previous M phase until the beginning of DNA synthesis, is called G1 (G indicating gap). (wikipedia.org)
  • S phase (synthesis phase) is the part of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. (wikipedia.org)
  • Cooper, S. and Helmstetter, C. E. 1968 DNA synthesis during the division cycle of rapidly growing Escherichia coli. (wikipedia.org)
  • DNA polymerases isolated from cells and artificial DNA primers can be used to initiate DNA synthesis at known sequences in a template DNA molecule. (wikipedia.org)
  • Signal Transduction
  • the outer layer of epidermal cell to the genome, fluencing UV radiation takes recourse to the process of signal transduction either by UV induced damaged DNA or by wavelength specific photoreceptors. (springer.com)
  • control
  • Jurkat T cells overexpressing ATG5 or control cells were cultured in the presence and absence of 3-MA for 48 h. 3-MA blocked the formation of LC3-II and p62 degradation, indicating that it indeed inhibited ATG5-induced autophagy. (nih.gov)
  • ATM and ATR may cooperate in ionizing radiation (IR)-induced G 2 -M checkpoint control, but ATM seems to be more dominant at the early stage of checkpoint activation and ATR seems to contribute mainly to sustained checkpoint events. (aacrjournals.org)
  • Overall, the data remain consistent with the hypothesis that overcoming HRS is related to the control of a specific G2 checkpoint that responds to radiation-mediated DNA damage. (aacrjournals.org)
  • The aim of the present study was to identify genes related to per2 expression and involved in cell cycle control. (springer.com)
  • During the early postnatal development of the cerebellum, Btg2 is mainly required to control the migration and differentiation of the precursor cells of cerebellar granule neurons. (wikipedia.org)
  • activation
  • Invariant NK T (iNKT) cells can provide help for B cell activation and Ab production. (jove.com)
  • Because B cells are also capable of cytokine production, Ag presentation, and T cell activation, we hypothesized that iNKT cells will also influence these activities. (jove.com)
  • HRS was expressed solely in MSH2+ cells and was associated with efficient activation of the early G2-phase cell cycle checkpoint. (jove.com)
  • We observed in a series of 6 cell lines that caspase-3 activation in the low-dose range mirrored the presence of HRS. (aacrjournals.org)
  • Initial assessment in 10 melanoma cell lines revealed that TMZ resistance correlated with MGMT expression (r = 0.79, p = 0.009), and in MGMT-proficient cell lines, with phospho-IGF-1R (r = 0.81, p = 0.038), suggesting that TMZ resistance associates with IGF-1R activation. (plymouth.ac.uk)
  • Activation of each phase is dependent on the proper progression and completion of the previous one. (wikipedia.org)
  • Thus, Clb5 and Clb6 are engaged in a positive feedback loop to promote their own activation during this period of the cell cycle. (wikipedia.org)
  • In addition, Cdc6p overexpression in primary cells may promote DNA hyperreplication and induce a senescence response similar to that caused by oncogene activation. (wikipedia.org)
  • embryonic stem
  • The recently developed ability to generate immortalized "normal" cell lines of a given differentiated phenotype from human embryonic stem cells has enhanced the ability to study cells of a normal genotype from a single source. (nih.gov)
  • regulatory
  • Additionally, CD4(+) iNKT cells induced expansions of cells with phenotypes of regulatory B cells. (jove.com)
  • CD1d-restricted invariant natural killer T (iNKT) cells have diverse immune stimulatory/regulatory activities through their ability to release cytokines and to kill or transactivate other cells. (jove.com)
  • progresses
  • As the cell progresses through G1, depending on internal and external conditions, it can either delay G1, enter a quiescent state known as G0, or proceed past the restriction point. (wikipedia.org)
  • transition
  • After a constant, organism-specific number of cleavages, many metazoan embryos undergo the mid-blastula transition (MBT), which initiates extensive cell cycle remodeling. (upenn.edu)
  • The concentration of Dbf4 at the G1/S transition of the cell cycle is higher than the concentration at the M/G1 transition. (wikipedia.org)
  • onset
  • On the onset of the S phase, Cdc6p gets phosphorylated by the Cdc28-Clb5-Clb6 complex (Cdk2) and consequently becoming inactivated. (wikipedia.org)
  • tumors
  • One of the major limitations of radiotherapy is that the cells of solid tumors become deficient in oxygen. (wikipedia.org)
  • Angiogenesis in tumors permits the growth and invasiveness of cancer cells leading to metastasis to distant organs ( 3 , 4 ). (aacrjournals.org)
  • However, many of the biochemical characteristics initially thought to be closely associated with the malignant phenotype of cells in culture were subsequently found to be dissociable from the ability of those cells to produce tumors in animals. (nih.gov)
  • Some of these characteristics may be seen both in transformed cells in culture and in tumors growing in vivo in experimental animals or patients. (nih.gov)
  • induce
  • In fact, in the neuronal PC12 cell line BTG2 is not able to trigger differentiation by itself, but only to synergize with NGF, while in vivo BTG2 is fully able to induce differentiation of progenitor cells, i.e., during embryonic development in the neuroblast of the neural tube and in granule precursors of cerebellum, as well in adult progenitor cells of the dentate gyrus and of the subventricular zone. (wikipedia.org)
  • Nucleus
  • In bacteria, which lack a cell nucleus, the cell cycle is divided into the B, C, and D periods. (wikipedia.org)
  • Interphase is a series of changes that takes place in a newly formed cell and its nucleus, before it becomes capable of division again. (wikipedia.org)
  • damage
  • Organic ITCs are generated due to hydrolysis of corresponding glucosinolates through catalytic mediation of myrosinase, which is released on damage of the plant cells during processing (cutting or chewing) of cruciferous vegetables. (aacrjournals.org)
  • DNA damage checkpoint acquisition does not require zygotic transcription. (upenn.edu)
  • Checkpoints are enabled through sensing DNA damage, transducing damage signals, and activating effectors. (aacrjournals.org)
  • citation needed] Damage to DNA is detected and fixed during S-phase. (wikipedia.org)
  • BTG2 was then isolated in human cells as sequence induced by p53 and DNA damage. (wikipedia.org)
  • radiation
  • Low-dose hyper-radiosensitivity (HRS) describes the increased radiosensitivity of cells to doses of ionizing radiation less than ∼0.5 Gy. (aacrjournals.org)
  • Moreover, distinct temporal differences in G2 checkpoint response were observed between these two cell lines within the low dose radiation range (0-1 Gy). (aacrjournals.org)
  • strand breaks, it was determined that the detection of radiation-induced strand breaks was comparable in a panel of cell lines that show disparate HRS status. (aacrjournals.org)
  • This suggests that immediate radiation-mediated DNA events may not have a prominent role in determining HRS, although this result needs to be confirmed with pure G2-phase cell populations. (aacrjournals.org)
  • Distinct
  • Furthermore, subsets of iNKT cells based on CD4 and CD8 expression that have distinct functional activities may differentially affect B cell functions. (jove.com)
  • Although the various stages of interphase are not usually morphologically distinguishable, each phase of the cell cycle has a distinct set of specialized biochemical processes that prepare the cell for initiation of cell divisions. (wikipedia.org)
  • Genes
  • Total RNA from cancer tissue of these patients was used to specify genes associated with altered per2 expression using the Human Cell Cycle RT 2 profiler PCR array system. (springer.com)