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.
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.
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.
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.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
The period of the CELL CYCLE following DNA synthesis (S PHASE) and preceding M PHASE (cell division phase). The CHROMOSOMES are tetraploid in this point.
Genes that code for proteins that regulate the CELL DIVISION CYCLE. These genes form a regulatory network that culminates in the onset of MITOSIS by activating the p34cdc2 protein (PROTEIN P34CDC2).
A 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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
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.
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.
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.
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.
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.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
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.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The cellular signaling system that halts the progression of cells through MITOSIS or MEIOSIS if a defect that will affect CHROMOSOME SEGREGATION is detected.
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).
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.
A subclass of dual specificity phosphatases that play a role in the progression of the CELL CYCLE. They dephosphorylate and activate CYCLIN-DEPENDENT KINASES.
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.
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.
The process by which a DNA molecule is duplicated.
An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase.
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.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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.
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.
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.
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.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
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.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
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.
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.
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.
A genus of ascomycetous fungi of the family Schizosaccharomycetaceae, order Schizosaccharomycetales.
A cyclin B subtype that colocalizes with MICROTUBULES during INTERPHASE and is transported into the CELL NUCLEUS at the end of the G2 PHASE.
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.
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.
Nocodazole is an antineoplastic agent which exerts its effect by depolymerizing microtubules.
A cell line derived from cultured tumor cells.
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.
Established cell cultures that have the potential to propagate indefinitely.
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.
Interruptions in the sugar-phosphate backbone of DNA, across both strands adjacently.
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.
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.
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.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
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)
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.
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.
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.
Proteins found in any species of fungus.
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.
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.
Tumor suppressor genes located on the short arm of human chromosome 17 and coding for the phosphoprotein p53.
Large multiprotein complexes that bind the centromeres of the chromosomes to the microtubules of the mitotic spindle during metaphase in the cell cycle.
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.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A 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).
A 50-kDa protein that complexes with CYCLIN-DEPENDENT KINASE 2 in the late G1 phase of the cell cycle.
3-Hydroxy-4-oxo-1(4H)-pyridinealanine. An antineoplastic alanine-substituted pyridine derivative isolated from Leucena glauca.
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.
An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA.
Enzymes that are involved in the reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule, which contained damaged regions.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Compounds that inhibit cell production of DNA or RNA.
The chromosomal constitution of a cell containing multiples of the normal number of CHROMOSOMES; includes triploidy (symbol: 3N), tetraploidy (symbol: 4N), etc.
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).
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.
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.
An antineoplastic compound which also has antimetabolite action. The drug is used in the therapy of acute leukemia.
The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.
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.
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.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
Elements of limited time intervals, contributing to particular results or situations.
Enzymes that catalyze the release of mononucleotides by the hydrolysis of the terminal bond of deoxyribonucleotide or ribonucleotide chains.
Transport proteins that carry specific substances in the blood or across cell membranes.
A type of chromosomal aberration involving DNA BREAKS. Chromosome breakage can result in CHROMOSOMAL TRANSLOCATION; CHROMOSOME INVERSION; or SEQUENCE DELETION.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
Deoxyribonucleic acid that makes up the genetic material of fungi.
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.
Drugs used to potentiate the effectiveness of radiation therapy in destroying unwanted cells.
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.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
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.
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.
The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.
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.
The orderly segregation of CHROMOSOMES during MEIOSIS or MITOSIS.
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.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
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.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
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)
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.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A suspected industrial carcinogen (and listed as such by OSHA). Its N-hydroxy metabolite is strongly carcinogenic and mutagenic.
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.
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.
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.
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.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
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.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
The functional hereditary units of FUNGI.
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.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
The phase of cell nucleus division following METAPHASE, in which the CHROMATIDS separate and migrate to opposite poles of the spindle.
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).
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.
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.
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.
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.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
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)
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.
Agents obtained from higher plants that have demonstrable cytostatic or antineoplastic activity.
Enzymes that catalyze the transfer of multiple ADP-RIBOSE groups from nicotinamide-adenine dinucleotide (NAD) onto protein targets, thus building up a linear or branched homopolymer of repeating ADP-ribose units i.e., POLY ADENOSINE DIPHOSPHATE RIBOSE.
A Rec A recombinase found in eukaryotes. Rad51 is involved in DNA REPAIR of double-strand breaks.
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.
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.
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.
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.
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.
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)
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
A 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.
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.
The degree of replication of the chromosome set in the karyotype.
Compounds that inhibit the activity of DNA TOPOISOMERASE I.
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.
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.
A quiescent state of cells during G1 PHASE.
Interruption or suppression of the expression of a gene at transcriptional or translational levels.
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).
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.
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.-.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
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.
Agents that inhibit PROTEIN KINASES.
The relationship between the dose of an administered drug and the response of the organism to the drug.
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.
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.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
Cellular DNA-binding proteins encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis.
A nitrosoguanidine derivative with potent mutagenic and carcinogenic properties.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
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.
Tumors or cancer of the human BREAST.
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.
Tumors or cancer of the COLON.
The rate dynamics in chemical or physical systems.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Genes that inhibit expression of the tumorigenic phenotype. They are normally involved in holding cellular growth in check. When tumor suppressor genes are inactivated or lost, a barrier to normal proliferation is removed and unregulated growth is possible.
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.
Defective nuclei produced during the TELOPHASE of MITOSIS or MEIOSIS by lagging CHROMOSOMES or chromosome fragments derived from spontaneous or experimentally induced chromosomal structural changes.
A group of enzymes catalyzing the endonucleolytic cleavage of DNA. They include members of EC 3.1.21.-, EC 3.1.22.-, EC 3.1.23.- (DNA RESTRICTION ENZYMES), EC 3.1.24.- (DNA RESTRICTION ENZYMES), and EC 3.1.25.-.
A genotoxicological technique for measuring DNA damage in an individual cell using single-cell gel electrophoresis. Cell DNA fragments assume a "comet with tail" formation on electrophoresis and are detected with an image analysis system. Alkaline assay conditions facilitate sensitive detection of single-strand damage.
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.
A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.
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.
A class of weak acids with the general formula R-CONHOH.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the BASE PAIR MISMATCH and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. (from Oxford Dictionary of Biochemistry and Molecular Biology, 2001)
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.
Proteins prepared by recombinant DNA technology.
An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.

Comparison of efficacy and toxicity profile between intraperitoneal and intravenous topotecan in human ovarian cancer xenografts. (1/1169)

OBJECTIVE: To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice. METHOD: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xenografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg x 2, 3.0 mg/kg x 2, 6.0 mg/kg x 2 or 10.0 mg/kg x 1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg x 2 or 10.0 mg/kg x 1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis. RESULTS: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation. CONCLUSION: The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.  (+info)

Cigarette smoke extract inhibits the proliferation of alveolar epithelial cells and induces apoptosis. (2/1169)

Cigarette smoke extract (CSE) contains abundant oxidants and free radicals. Oxidative stress caused by cigarette smoking results in the destruction of the alveolar cell walls and emphysema. However, there exists discrepancy about how CSE works in the process. In the present study, we observed the effect of CSE on the cell growth of type II alveolar epithelial cell-derived A549 cell line, and provided molecular understanding of this effect. The MTT assay results showed that CSE decreased the cell viability of A549 cells in a dose- and time-dependent manner, and cell cycle was arrested in G(1)/S phase. Furthermore, CSE-induced apoptosis of A549 cells was verified by Hoechst 33258 staining, electron microscopy in morphology, and the appearance of DNA fragmentation and annexin V-FITC/propidium iodide (PI) staining assay at molecular level. It was found that CSE treatment resulted in the upregulation of Fas/APO-1 receptor and activation of caspase-3. CSE also initiated accumulation of intracellular reactive oxygen species, which was detected by laser confocal microscopy. Taken together, CSE could inhibit the cell growth and induce apoptosis of A549 cells through Fas receptor pathway. Oxidative stress caused by CSE may be the radical factor leading to apoptosis as well as cell growth inhibition in alveolar epithelial cells.  (+info)

Glycogen synthase kinase 3beta induces cell cycle arrest in a cyclin D1-dependent manner in human lung adenocarcinoma cell line A549. (3/1169)

The effect of glycogen synthase kinase 3beta (GSK3beta) has been repeatedly implicated in cell proliferation, but studies on the effect of GSK3beta in different cell lines with different stimuli have drawn different conclusions. To investigate the direct effect of GSK3beta on cell growth in human lung adenocarcinoma cell line A549, we changed its activity by transient transfection with two kinds of GSK3beta mutant plasmids, constitutively active form S9A-GSK3beta and dominant negative form KM-GSK3beta. Twenty-four hours later, cell counting, flow cytometry and Western blot detection were made respectively. The results showed that enhancing GSK3beta activity caused a decrease in cell number, as well as a higher percentage of cells at G(1) phase. Further, the expression of cyclin D1 was down-regulated by GSK3beta. Taken together, our observations suggest that GSK3beta may induce G(1) cell cycle arrest in a cyclin D1-dependent fashion and therefore possibly plays a growth-inhibitory role in A549 cells.  (+info)

Adenine nucleotide translocase 4 deficiency leads to early meiotic arrest of murine male germ cells. (4/1169)


Silencing CENPF in bovine preimplantation embryo induces arrest at 8-cell stage. (5/1169)


Silencing of the IKKepsilon gene by siRNA inhibits invasiveness and growth of breast cancer cells. (6/1169)


SR and SR-related proteins redistribute to segregated fibrillar components of nucleoli in a response to DNA damage. (7/1169)


Unliganded progesterone receptors attenuate taxane-induced breast cancer cell death by modulating the spindle assembly checkpoint. (8/1169)


Cyclic GMP (cGMP)-dependent protein kinase (protein kinase G [PKG]) is essential for microneme secretion, motility, invasion, and egress in apicomplexan parasites, However, the separate roles of two isoforms of the kinase that are expressed by some apicomplexans remain uncertain. Despite having identical regulatory and catalytic domains, PKGI is plasma membrane associated whereas PKGII is cytosolic in Toxoplasma gondii. To determine whether these isoforms are functionally distinct or redundant, we developed an auxin-inducible degron (AID) tagging system for conditional protein depletion in T. gondii. By combining AID regulation with genome editing strategies, we determined that PKGI is necessary and fully sufficient for PKG-dependent cellular processes. Conversely, PKGII is functionally insufficient and dispensable in the presence of PKGI. The difference in functionality mapped to the first 15 residues of PKGI, containing a myristoylated Gly residue at position 2 that is critical for membrane ...
A recent in-depth view of cell cycle regulation and cancer has provided novel samples of research at the Frontiers of Science. However, the number of foremost revealing information about both the topics has been derived from the intersection of these two fields.1-5 This review intends to introduce the basics of the cell cycle and its regulation at different checkpoints in relation to cancer. Cancer is broadly a result of unchecked cell multiplication due to abnormal activity of varied cell cycle proteins; therefore, cell cycle regulators are considered attractive targets in cancer therapy. Many cancers are uniquely linked with these proteins and are therefore selectively sensitive to their inhibition.6 After a long run of research on the physiological functions of cell cycle proteins and their relevance for cancer, these data recently got converted into the first approved cancer therapeutics, targeting the regulator of cell cycle.7 Here, we are reviewing the role of cell cycle proteins in ...
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Cell cycle analysis is commonly used in biomedical research studies and clinical diagnosis. It helps in distinguishing cells that are in different phases of cell cycle and used to determine the cellular response to biological stimulations and various drug
The cell membrane The DNA Hello, today we will be learning about the cell cycle. The cell cycle is a process that cells go through in order to divide.
Drag the Labels Onto the Diagram to Identify the Stages Of the Cell Cycle. - Drag the Labels Onto the Diagram to Identify the Stages Of the Cell Cycle. , Ponents Of Blood Article
The most recent publications in Cell Cycle Checkpoints and accross biochemistry, molecular biology, neuroscience, development, biotechnology and medicine.
CELL CYCLE CHECKPOINTS The cell cycle has regulatory points called checkpoint. A check point is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cell cycle can be halted until conditions are favourable (e.g. the DNA is repaired). These checkpoints occur near […]. ...
Great news, we have finally launched a website devoted to the Australian Cell Cycle community ! This site will serve as a hub for all the amazing cell cycle research that is performed in Australia. In addition, we will also be rebooting the Australian Cell Cycle Workshop (ACCW), with a tentative date of early April…
Cell cycle in somatic cells vs. ESCs. (a) Cell cycle regulation in somatic cells: mitogen signaling through MAPK path
Hva er Cell Cycle Analysis? Cellesyklus-analyse er en teknikk som brukes i biokjemisk forskning for å identifisere og analysere fasen av en biologisk celle. I løpet av sin levetid, passerer en celle gjennom en serie av sykliske faser som kollektivt er kjent som cellesyklusen. M
Cell cycle, the ordered sequence of events that occur in a cell in preparation for cell division. The cell cycle is a four-stage process in which the cell increases in size, copies its DNA, prepares to divide, and divides. Learn more about the cell cycle and the proteins that regulate its progression.
Introduction to Cell Cycle: The cell cycle is the process by which a cell replicates its genetic material and synthesized the other elements of the cell
Identify the correct order of phases for the cell cycle? I. G 2 ​ phase- growth and preparation for mitosis II. Mitosis III. G 1 ​ phase- cell growth IV. S pha
The cell cycle is the meticulous series of events that parent cells go through as they grow and divide their cellular material between two new daughter... read full [Essay Sample] for free
Hello.. It appears Im stuck on another question. Ive figured out 3/4 of it, but I cant seem to find ANYWHERE in my textbook, anything about the stages of the cell cycle and cancer. If you can help me, that would be great ...
Find right answers right now! Which of the following is a correct statement about the events of the cell cycle? More questions about Science & Mathematics, which
worksheets : Cells Alive Worksheet Beautiful Cells Alive Cell Cycle Worksheet Promotiontablecovers Cells Alive Worksheet ~ zachemig2018
Quiescence is a temporary cell cycle state where populations of cells rest and do not replicate, before they are activated and re-enter the cell cycle.
If you have a question about this talk, please contact Laura Blackburn.. Abstract not available. This talk is part of the Lectures in Cancer Biology and Medicine series.. ...
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We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly ...
Welcome to the Australian Cell Cycle Community website. This page is dedicated to bringing together all of the amazing research related to the cell cycle that is performed throughout Australia.
The cell cycle is the life of a cell from the time it is first formed from a dividing parent cell until its own division into two cells. Cell division involves the distribution of identical DNA to two daughter cells. A dividing cell duplicates its DNA,...
The longest phase of the cell cycle is the Gap 1 phase, or G1 phase. During this phase, the cell gears up for cell division by amassing more organelles and getting larger....
Science 9 Chapter 5.1 The Cell Cycle and Mitosis Pg152-158 Notes Cell Replacement and Development -Cells continue to divide as you continue to grow. -
TY - CONF. T1 - Quality and yield improvement through modulation of cell cycle. AU - De Veylder, L.. AU - Beeckman, T.. AU - Beemster, G.. AU - Salmenkallio-Marttila, Marjatta. AU - Oksman-Caldentey, Kirsi-Marja. AU - Inze, D.. PY - 2001. Y1 - 2001. M3 - Conference article. SP - 13. EP - 14. ER - ...
See 13 Best Images of Cell Cycle And Mitosis Worksheet Answers. Inspiring Cell Cycle and Mitosis Worksheet Answers worksheet images. Cell Cycle Worksheet Answers Cell Cycle and Mitosis Worksheet Answer Key Cell Cycle Mitosis and Meiosis Test Answers Cell Cycle Worksheet Answer Key Cell Division Mitosis Worksheet and Answers
View Notes - Cell Cycle from BIOL 101 at UNC. Cell Cycle, Mitosis Meiosis Tuesday, February 10, 2009 10:19 AM 1. Cell Cycle aka Life of a Cell o Interphase Secreting Not dividing o Mitosis Nuclear
補充影片: Dave Morgan Honor Biology: 生物學特論 Lecture 12: Cell cycle and check point control Part 1 Honor Biology: 生物學特論 Lecture 12: Cell cycle and check point control Part 2 Honor Biology: 生物學特論 Lecture 12: Cell cycle and check point contr ...
View Notes - bild lecture week 5.2 from BIOLOGY bild 1 at UCSD. Review: Monday. Skip chapter 11. Review: PSII PSI NADPH Mitosis and Cell Cycle 1.) Cell Cycle a. Alternates between interphase and
2 of 4 of my cell cycle unit. Image Credits: Biology (Campbell) 9th edition, copyright Pearson 2011, & The Internet. Provided under the terms of a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. By David Knuffke.
Research groupsCell biology and Biotechnology Role of Hsp90 in cell cycle control and ageing Dr Andrés Garzón Villar. ..
Get all questions and answers of Cell Cycle And Cell Division of NEET1 Structures And Functions on TopperLearning. TopperLearnings Experts and Students has answered all of Cell Cycle And Cell Division of NEET1 Structures And Functions questions in detail.
Kinases Available in QuickScout™ Cell Cycle panel. The QuickScout™ Cell Cycle Panel mainly includes kinases which are directly involved in the cell-cycle, and their inhibition may interfere with cell proliferation. Contact us to learn more about this panel and how we can help you identify the clinical potential of your compounds.. ...
Class 11 Biology Notes for Cell Cycle and Cell Division - Get here the Notes, Question & Practice Paper of Class 11 Biology for topic Cell Cycle and Cell
Cell Cycle & Cell Division objective MCQs and Study Notes to help you in NEET Biology preparation. Get important Cell Cycle & Cell Division NEET MCQs, tips and important topics
The cell cycle constitutes a series of stages that allow a cell to double its cellular components and divide into two daughter cells. Cell cycle and division are crucial for development of a multicellular organism, as well as...
Shop for the cell cycle recombinant proteins you need here at ProSci Inc.! We stock a wide selection of proteins of all kinds. Visit us online today.
The cell cycle is a five-stage process that begins with the prophase stage and ends with the cytokinesis stage. In between the beginning and end stages, the dividing cell passes through the stages of...
Research groupsCell biology and Biotechnology Cell cycle in yeast Dr Juan Jiménez Martínez. UPOPrincipal Investigator ..
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welcome Today I well be teaching and showing you the cell cycle DNA The first step of the cell cycle is Interphase it when the DNA in the cell makes a
Nutr Cancer 63: 435- 443. Jaganathan SK( 2011) Can escapes from developmental aspects of the suggest oil film? Med Hypotheses 76: 535- 537.
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How To Run a Recomp Cycle I hear this all the time I want to get bigger and rip up a bit Starting my cycle, looking to lean up and
Reece, Jane B. (2011). "12". The Cell Cycle (9th ed.). San Francisco: Pearson Education, Inc. May, Karen M; Kevin G. Hardwick ( ... 2006). "The spindle checkpoint". Journal of Cell Science. 119 (Pt 20): 4139-42. doi:10.1242/jcs.03165. PMID 17038540. Retrieved ... Forces exerted by protein "motors" associated with spindle microtubules move the chromosomes toward the centre of the cell. ... Prometaphase is the phase of mitosis following prophase and preceding metaphase, in eukaryotic somatic cells. In prometaphase, ...
Cell Cycle. 4 (7): 883-888. doi:10.4161/cc.4.7.1791. PMID 15970698. Ringshausen, Ingo; O'Shea, Clodagh C.; Finch, Andrew J.; ... O'Shea, Clodagh C.; Choi, Serah; McCormick, Frank; Stokoe, David (2 May 2005). "Adenovirus Overrides Cellular Checkpoints for ... doi:10.1016/j.cell.2015.07.058. PMC 4681434. PMID 26317467. Higginbotham, Jennifer M.; O'Shea, Clodagh C. (15 October 2015). ... Clodagh C. O'Shea is a professor of molecular and cell biology and current Wicklow Chair at the Salk Institute for Biological ...
After DNA damage, cell cycle checkpoints are activated. Checkpoint activation pauses the cell cycle and gives the cell time to ... After rapid chromatin remodeling, cell cycle checkpoints are activated to allow DNA repair to occur before the cell cycle ... It leads to a pause in cell cycle allowing the cell time to repair the damage before continuing to divide. Checkpoint Proteins ... and some genes are involved in both DNA damage repair and cell cycle checkpoint control, for example ATM and checkpoint kinase ...
"Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2". The Journal of Cell ... Defects in BUB3 in the cell cycle can contribute to the following diseases: hepatocellular carcinoma gastric cancer breast ... "Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2". The Journal of Cell ... Yu H (December 2002). "Regulation of APC-Cdc20 by the spindle checkpoint". Current Opinion in Cell Biology. 14 (6): 706-14. doi ...
It is used to understand cell cycle checkpoints. Researchers are working to find a way to use this gene to create anti-cancer ... If MCR 1 is not present in the cell these check points do not work properly. Yin L, Locovei AM, D'Urso G (October 2008). " ... The most common function is found during the cell cycle when mutations occur because it becomes activated without ... "Activation of the DNA damage checkpoint in mutants defective in DNA replication initiation". Mol. Biol. Cell. 19 (10): 4374-82 ...
βTrCP plays important roles in regulating cell cycle checkpoints. In response to genotoxic stress, it contributes to turn off ... Cell cycle regulators constitute a major group of βTrCP substrates. During S phase, βTrCP keeps CDK1 in check by promoting the ... thereby preventing cell cycle progression before the completion of DNA repair. During recovery from DNA replication and DNA ... "SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response". Molecular Cell. ...
Elledge SJ (December 1996). "Cell cycle checkpoints: preventing an identity crisis". Science. 274 (5293): 1664-1672. Bibcode: ... Kaldis P, Aleem E (2007). "Cell cycle sibling rivalry: Cdc2 vs. Cdk2". Cell Cycle. 4 (11): 1491-1494. doi:10.4161/cc.4.11.2124 ... ISBN 978-0-19-920610-0. Nasmyth K (April 1993). "Control of the yeast cell cycle by the Cdc28 protein kinase". Curr. Opin. Cell ... Zhao RY, Elder RT (2005). "Viral infections and cell cycle G2/M regulation". Cell Res. 15 (3): 143-149. doi:10.1038/ ...
These proteins are key checkpoint proteins in the cell cycle. Cancer patients have a lowered expression of per1. Gery, et al. ... PER1 expression may have significant effects on the cell cycle. Cancer is often a result of unregulated cell growth and ... "The circadian gene per1 plays an important role in cell growth and DNA damage control in human cancer cells". Mol. Cell. 22 (3 ... Therefore, a cell's circadian clock may play a large role in its likelihood of developing into a cancer cell. PER1 is a gene ...
Borlado LR, Méndez J (February 2008). "CDC6: from DNA replication to cell cycle checkpoints and oncogenesis". Carcinogenesis. ... Cdc6, or cell division cycle 6, is a protein in eukaryotic cells. It is mainly studied in the budding yeast Saccharomyces ... CDC6 is normally present at high levels during the G1 phase of the cell cycle. This is partly because the CDC6 gene is only ... of DNA replication and plays important roles in the activation and maintenance of the checkpoint mechanisms in the cell cycle ...
Lu X, Nannenga B, Donehower LA (2005). "PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints". Genes Dev. ... and cell cycle control". Mol. Cell. Biol. 22 (4): 1094-105. doi:10.1128/MCB.22.4.1094-1105.2002. PMC 134641. PMID 11809801. Li ... Cell. 15 (4): 621-34. doi:10.1016/j.molcel.2004.08.007. PMID 15327777. Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The ... Cell Res. 288 (1): 35-50. doi:10.1016/S0014-4827(03)00130-7. PMID 12878157. Bernards R (2004). "Wip-ing out cancer". Nat. Genet ...
Callegari AJ, Kelly TJ (March 2007). "Shedding light on the DNA damage checkpoint". Cell Cycle. 6 (6): 660-6. doi:10.4161/cc. ... Melanoma cells are commonly defective in postreplication repair of DNA damages that are in the form of cyclobutane pyrimidine ... Molecular Cell Biology. 6 (12): 943-53. doi:10.1038/nrm1781. PMID 16341080. Brash DE, Seidman MM (January 2020). "Defective ... At damaged sites in the genome, both prokaryotic and eukaryotic cells utilize a number of postreplication repair (PRR) ...
The Start checkpoint is a major cell cycle checkpoint in yeast. The Start checkpoint ensures irreversible cell-cycle entry even ... Thus, larger cells spend less time in the Start checkpoint compared to smaller cells. Morgan, David. The Cell Cycle: Principles ... "Distinct Interactions Select and Maintain a Specific Cell Fate." Molecular Cell 43.4 (2011): 528-39. Mitosis Cell cycle S-phase ... a cell cycle gene, showed great coexpression in STE5-8A cells relative to wild type cells. Thus, Cln1/2 inhibition of Far1 ...
Stabilization of p53 by CHK2 leads to cell cycle arrest in phase G1. Furthermore, CHK2 is known to phosphorylate the cell-cycle ... The CHEK2 gene encodes for checkpoint kinase 2 (CHK2), a protein that acts a tumor suppressor. CHK2 regulates cell division, ... In the fruit fly Drosophila, irradiation of germ line cells generates double-strand breaks that result in cell cycle arrest and ... "Chk2 regulates cell cycle progression during mouse oocyte maturation and early embryo development". Mol. Cells. 37 (2): 126-32 ...
E2F integrates cell cycle progression with DNA repair, and G2(M) checkpoints., Genes and Development 16 (2002) 245-56. Johnson ... V.R. Iyer, C.E. Horak, C.S. Scafe, D. Botstein, M. Snyder, P.O. Brown, Genomic binding sites of the yeast cell-cycle ... Then, the cells are lysed and the DNA is sheared by sonication or using micrococcal nuclease. This results in double-stranded ... Last, during the dry-lab portion of the cycle, gathered data are analyzed to either answer the initial question or lead to new ...
Yeast are a popular species for study because of the rapid cell cycle. Rb is one of the most studied checkpoint molecules. It ... In a healthy cell, checkpoints between phases permit a new phase to begin only when the previous phase is complete and ... Cyclins are molecules that manage the timing of cell cycle events. Cyclin dependent kinases pair up with cyclins to become ... Cyclins are named because they are created or destroyed at predetermined points within the cell cycle. Kinase inhibitors add ...
Cell Cycle. 7 (17): 2720-6. doi:10.4161/cc.7.17.6580. PMID 18758239. Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, Hwang ... SG, Chun JS, Lee CW (September 2004). "WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors ... In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the ... Those cancer cells can form cell-cell adhesions again and return to an epithelial state. Inherited inactivating mutations in ...
He proposed the existence of cell cycle checkpoints, tumor suppressor genes and oncogenes. He speculated that cancers might be ... During the same period, the idea that the body was made up of various tissues, that in turn were made up of millions of cells, ... A Conspiracy of Cells: One Woman's Immortal Legacy and the Medical Scandal It Caused. ISBN 978-0-88706-099-1. "Harald zur ... He discovered a method to generate cells with multiple copies of the centrosome, a structure he discovered and named. He ...
One of the cell cycle checkpoints occurs during prometaphase and metaphase. Only after all chromosomes have become aligned at ... "The Cell Cycle". Kimball's Biology Pages. Archived from the original on 19 November 2012. Retrieved 9 December 2012. Media ... Metaphase (from the Greek μετά, "adjacent" and φάσις, "stage") is a stage of mitosis in the eukaryotic cell cycle in which ... Metaphase accounts for approximately 4% of the cell cycle's duration.[citation needed] Preceded by events in prometaphase and ...
Checkpoints are eukaryotic DNA damage-inducible cell cycle arrests at G1 and G2. Checkpoint suppressor 1 suppresses multiple ... Mol Cell Biol. 17 (6): 3037-46. PMC 232156. PMID 9154802. "Entrez Gene: CHES1 checkpoint suppressor 1". Maruyama K, Sugano S ( ... Pati D, Keller C, Groudine M, Plon SE (Jun 1997). "Reconstitution of a MEC1-independent checkpoint in yeast by expression of a ... yeast checkpoint mutations including mec1, rad9, rad53 and dun1 by activating a MEC1-independent checkpoint pathway. ...
The BRCT domain is found predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage, for ... "A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins". FASEB J. 11 (1): 68-76. doi: ...
This protein is required for cell cycle progression through the S/M checkpoint. Three transcript variants encoding different ... The effect of NEDD8 inhibition may be greater for cancer cells than for normal cells if the cancer cells are already deficient ... "The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in ... "The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in ...
... fluoropyrimidines increase sensitivity by dysregulating S-phase cell cycle checkpoints in tumor cells. Gemcitabine progresses ... 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 ... One of the major limitations of radiotherapy is that the cells of solid tumors become deficient in oxygen. Solid tumors can ...
... a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein ... Cell cycle checkpoint protein RAD17 is a protein that in humans is encoded by the RAD17 gene. The protein encoded by this gene ... "Phosphorylation of serines 635 and 645 of human Rad17 is cell cycle regulated and is required for G1/S checkpoint activation in ... "The human checkpoint Rad protein Rad17 is chromatin-associated throughout the cell cycle, localizes to DNA replication sites, ...
"E2F integrates cell cycle progression with DNA repair, replication, and G(2)/M checkpoints". Genes & Development. 16 (2): 245- ... The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target ... Lindeman GJ, Gaubatz S, Livingston DM, Ginsberg D (May 1997). "The subcellular localization of E2F-4 is cell-cycle dependent". ... This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner. Alternative gene splicing is ...
... a novel human gene that complements a fission yeast cell cycle checkpoint mutation". Mol. Biol. Cell. 6 (10): 1411-21. doi: ... J. Physiol., Cell Physiol. 287 (1): C30-5. doi:10.1152/ajpcell.00443.2003. PMID 14985236. v t e. ... 2002). "Antigenic and functional properties of the human red blood cell urea transporter hUT-B1". J. Biol. Chem. 277 (37): ... 1995). "Cloning and functional expression of a urea transporter from human bone marrow cells". J. Biol. Chem. 269 (50): 31649- ...
... a regulatory link between the circadian and cell cycles". Science. 313 (5787): 644-9. doi:10.1126/science.1121716. PMID ... Pregueiro AM, Liu Q, Baker CL, Dunlap JC, Loros JJ (2006). "The Neurospora checkpoint kinase 2: ... A description of the regulation of frq and FRQ requires a description of the clock cycle. The molecular basis of the circadian ... At a later time, and with kinetics that do not influence the circadian cycle, this hyperphosphorylated FRQ is degraded through ...
"GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic ... inhibits cell growth and induces cell cycle G2/M arrest for hepatoma Hep-G2 cell lines". Mol. Biol. Rep. 30 (4): 249-53. doi: ... Such stress causes DNA damage to which IM cells respond with cell cycle arrest. All three GADD45 isoforms GADD45A, GADD45B, and ... GADD45G and GADD45A act redundantly to control cell growth, allow the cells to move from pluripotentcy helping cells ...
Prekeris R (2015). "Cut or NoCut: the role of JADE1S in regulating abscission checkpoint". Cell Cycle. 14 (20): 3219. doi: ... "Cell cycle-dependent chromatin shuttling of HBO1-JADE1 histone acetyl transferase (HAT) complex". Cell Cycle. 13 (12): 1885-901 ... Cells undergo morphological changes that do not resemble apoptosis but suggest severely impaired cell cycle including dyeing ... JADE1S but not JADE1L or HBO1 was found in centrosomes of dividing cells throughout the cell cycle, and neither of these ...
... cell cycle checkpoints may be activated to allow DNA repair to be completed before the cell cycle progresses. First, two ... per cell per day 55,200 Double-strand breaks Human cells, per cell cycle 10 50 O6-methylguanines Mammalian cells, per cell per ... where it blocks cell cycle progression. Activation of p53 can trigger cell death or permanent cell cycle arrest. p53 can also ... Throughout the cell cycle there are various checkpoints to ensure the cell is in good condition to progress to mitosis. The ...
"Specific association of estrogen receptor beta with the cell cycle spindle assembly checkpoint protein, MAD2". Proceedings of ... However, ERβ has been found to have proliferative effects in some breast cell lines. Expression of ERα and ERβ in the mammary ... ERβ may inhibit cell proliferation and opposes the actions of ERα in reproductive tissue. ERβ may also have an important role ... ERβ also plays a role in regulating APOE, a risk factor for AD that redistributes lipids across cells. APOE expression in the ...
chromosome organization involved in meiotic cell cycle. • mitotic recombination. • protein homooligomerization. • response to ... Esophageal squamous cell cancer. Over-expression. 47%. Immunohistochemistry. [24]. Renal cell carcinoma. Under-expression. 100% ... "MicroRNAs down-regulate homologous recombination in the G1 phase of cycling cells to maintain genomic stability". Elife. 3: ... "Association of BRCA1 with Rad51 in mitotic and meiotic cells". Cell. 88 (2): 265-75. doi:10.1016/s0092-8674(00)81847-4. PMID ...
SLBP levels are controlled by cell-cycle proteins, causing SLBP to accumulate as cells enter S phase and degrade as cells leave ... Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ (Feb 2003). "MDC1 is a mediator of the mammalian DNA damage checkpoint". ... Link between cell-cycle control machinery and histone synthesis[edit]. Nuclear protein Ataxia-Telangiectasia (NPAT), also known ... Masumoto H, Hawke D, Kobayashi R, Verreault A (Jul 2005). "A role for cell-cycle-regulated histone H3 lysine 56 acetylation in ...
Phosphorylation of the cell cycle inhibitor p21Cip1/WAF1 by Pim-1 kinase. „Biochim. Biophys. Acta". 1593 (1), s. 45-55, 2002. ... Identification of a functional domain in a GADD45-mediated G2/M checkpoint. „J. Biol. Chem.". 275 (47), s. 36892-8, 2000. DOI: ... Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21. „ ... P21Waf1/Cip1 dysfunction in neuroblastoma: a novel mechanism of attenuating G0-G1 cell cycle arrest. „Cancer Res.". 63 (13), s ...
Earlier cell cycle checkpoints such as post-restriction point check between G1 phase and S phase similarly involve proteasomal ... Cell cycle controlEdit. Cell cycle progression is controlled by ordered action of cyclin-dependent kinases (CDKs), activated by ... Apoptosis is mediated through disrupting the regulated degradation of pro-growth cell cycle proteins.[88] However, some cell ... Asher G, Shaul Y (August 2005). "p53 proteasomal degradation: poly-ubiquitination is not the whole story". Cell Cycle. 4 (8): ...
... the PDGFs allow a cell to skip the G1 checkpoints in order to divide.[21] It has been shown that in monocytes-macrophages and ... Downstream effects of this include regulation of gene expression and the cell cycle. The role of PI3K has been investigated by ... PDGF[1][2] is a potent mitogen for cells of mesenchymal origin, including fibroblasts, smooth muscle cells and glial cells. In ... "Cell Death and Control of Cell Survival in the Oligodendrocyte Lineage". Cell. 70 (1): 31-46. doi:10.1016/0092-8674(92)90531-G ...
regulation of cell cycle. • cell division. • negative regulation of cell cycle arrest. • protein phosphorylation. • lens ... Cell cycle checkpoints. *Restriction point. *Spindle checkpoint. *Postreplication checkpoint. Other cellular phases. *Apoptosis ... cell cycle. • positive regulation of G2/M transition of mitotic cell cycle. • response to toxic substance. • positive ... and CDK5 cell cycle kinase genes". Cytogenet. Cell Genet. 66 (1): 72-4. doi:10.1159/000133669. PMID 8275715.. ...
... also plays a role in cell-to-cell adhesion (a mechanism employed by cells of the immune system) via sugar-binding ... Secondly, N-linked glycans mediate a critical quality control check point in glycoprotein folding in the endoplasmic reticulum. ... Glycolysis → Pyruvate decarboxylation → Citric acid cycle → Oxidative phosphorylation (electron transport chain + ATP synthase) ... prevalent form of glycosylation and is important for the folding of many eukaryotic glycoproteins and for cell-cell and cell- ...
... delays cell cycle transition and/or proliferation.[18] In contrast, methylation of histone residues H3K4, H3K36, and H3K79 is ... "The Dot1 histone methyltransferase and the Rad9 checkpoint adaptor contribute to cohesin-dependent double-strand break repair ... stem cell maturation, cell lineage development, genetic imprinting, DNA methylation, and cell mitosis.[2] ... Kouzarides T (February 2007). "Chromatin modifications and their function". Cell. 128 (4): 693-705. doi:10.1016/j.cell.2007.02. ...
"A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade". Cell. 175 (4): 984-997.e24. doi:10.1016 ... Instead, in another temperature cycle, the loops are denatured, allowing the fragments to be amplified with PCR. MALBAC has ... "Pathogen Cell-to-Cell Variability Drives Heterogeneity in Host Immune Responses". Cell. 162 (6): 1309-21. doi:10.1016/j.cell. ... Single-cell genome (DNA) sequencing[edit]. Single-cell DNA genome sequencing involves isolating a single cell, amplifying the ...
"Cell Cycle. 8 (24): 4155-67. doi:10.4161/cc.8.24.10316. PMC 2896895 . PMID 19946220.. ... checkpoint inhibitor ipilimumab, CYP17 inhibitor galeterone (TOK-001), and immunotherapy PROSTVAC.[185] ... lo Prostate Cancer Cell Population Harbors Self-Renewing Long-Term Tumor-Propagating Cells that Resist Castration". Cell Stem ... LNCaP cells express androgen receptor (AR), but PC-3 and DU-145 cells express very little or no AR. AR, an androgen-activated ...
mitotic cell cycle checkpoint. • receptor clustering. • positive regulation of establishment of protein localization to plasma ... T cell cytokine production. • T cell activation. • peristalsis. • receptor localization to synapse. • single organismal cell- ... There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. In the brain, ... cell-cell junction. • bicellular tight junction. • node of Ranvier. • synapse. • perinuclear region of cytoplasm. • cytoplasmic ...
cell cycle arrest. • response to organonitrogen compound. • animal organ regeneration. • regulation of mitotic cell cycle. • ... but are defective in G1 checkpoint control". Cell. 82 (4): 675-684. doi:10.1016/0092-8674(95)90039-x.. ... G2/M transition of mitotic cell cycle. • positive regulation of B cell proliferation. • negative regulation of cell growth. • ... negative regulation of G1/S transition of mitotic cell cycle. • regulation of cell cycle. • intrinsic apoptotic signaling ...
... and other cell cycle proteins. The phases follow one another in strict order and there are "checkpoints" that give the cell ... Related cell processes[edit]. Cell rounding[edit]. Cell shape changes through mitosis for a typical animal cell cultured on a ... Cells may also temporarily or permanently leave the cell cycle and enter G0 phase to stop dividing. This can occur when cells ... The Cell-Cycle Ontology. * Interactive Visualization of the C. elegans Cell Lineage - Visualize the entire cell ...
"The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in ... regulation of cell cycle. • cellular protein modification process. • mitotic cell cycle. • endomitotic cell cycle. • cell cycle ... "The amyloid precursor protein-binding protein APP-BP1 drives the cell cycle through the S-M checkpoint and causes apoptosis in ... Gubin AN, Njoroge JM, Bouffard GG, Miller JL (1999). "Gene expression in proliferating human erythroid cells". Genomics. 59 (2 ...
and Fidelis, K. (1999) A sliding clamp model for the Rad1 family of cell cycle checkpoint proteins. Cell, 96: 769-770. ...
Cell Cycle. 7 (17): 2720-6. doi:10.4161/cc.7.17.6580. PMID 18758239.. ... "WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Letters. 575 (1-3 ... cell junction. • cytoplasm. • plasma membrane. Biological process. • negative regulation of cell-cell adhesion. • positive ... cell adhesion molecule binding. • cadherin binding. • identical protein binding. Cellular component. • cell-cell adherens ...
... bone marrow stem cells and the erythrocytes they produce through cell divisions are ideal candidates. These cells experience ... or flawed anaphase checkpoint genes.[2] Many micronucleus assays have been developed to test for the presence of these ... which gives rise to the macronuclei and micronuclei of the individuals of the next cycle of fission. ... displaystyle MN/cell=AF/cell*F}. AF is the number of acentric fragments and F = 0.5 - 0.5P, where P equals the probability of ...
... leading to cell death. Cell death in organisms is necessary for the normal development of cells and the cell cycle maturation.[ ... Cell cycle checkpoints. *Restriction point. *Spindle checkpoint. *Postreplication checkpoint. Other cellular phases. *Apoptosis ... HeLa cells are an immortalized cancer cell line used frequently in research. The cell line was established by removing cells ... p53 prevents the cell from replicating by stopping the cell cycle at G1, or interphase, to give the cell time to repair, ...
Cell cycle checkpoints. *Restriction point. *Spindle checkpoint. *Postreplication checkpoint. Other cellular phases. *Apoptosis ... single organismal cell-cell adhesion. • cell differentiation. • positive regulation of epithelial cell proliferation involved ... Cell division control protein 42 homolog, also known as Cdc42, is a protein involved in regulation of the cell cycle. It was ... Normal cancer cells and Cdc42-deficient cancer cells have also been compared in vivo. When both types of cells were injected ...
Durant ST, Nickoloff JA (2005). "Good timing in the cell cycle for precise DNA repair by BRCA1". Cell Cycle. 4 (9): 1216-22. ... mitotic G2/M transition checkpoint. • regulation of transcription from RNA polymerase II promoter. • negative regulation of G0 ... cell cycle. • double-strand break repair via nonhomologous end joining. • apoptotic process. • regulation of apoptotic process ... positive regulation of cell cycle arrest. • positive regulation of transcription from RNA polymerase II promoter. • positive ...
Just as in animals, plant cells differentiate and develop into multiple cell types. Totipotent meristematic cells can ... Land plants are key components of the water cycle and several other biogeochemical cycles. Some plants have coevolved with ... The DNA checkpoint kinase ATM has a key role in integrating progression through germination with repair responses to the DNA ... Cell division is also characterized by the development of a phragmoplast for the construction of a cell plate in the late ...
"Cell (dalam bahasa English). 155 (6): 1282-1295. doi:10.1016/j.cell.2013.10.054. ISSN 0092-8674. PMC 3894749 . PMID 24315098.. ... "De-novo and acquired resistance to immune checkpoint targeting". The Lancet Oncology (dalam bahasa Inggris). 18 (12): e731- ... "Secretory leukocyte protease inhibitor (SLPI) concentrations in cervical mucus of women with normal menstrual cycle" ... "Cell Stem Cell (dalam bahasa English). 15 (1): 14-25. doi:10.1016/j.stem.2014.06.009. ISSN 1934-5909. PMC 4131296 . PMID ...
Cell cycle checkpoints: preventing an identity crisis. Science. December 1996, 274 (5293): 1664-72. Bibcode:1996Sci...274.1664E ... 細胞週期(英語:cell cycle),是指能持续分裂的真核细胞从一次有丝分裂结束后生长,再到下一次分裂结束的循环过程。細胞週期的长短反映了细胞所处状态,这是一个细胞物质积累与细胞分裂的循环过程。癌变的细
Each photoreceptor cell consists of two main sections, the cell body and the rhabdomere. The cell body contains the nucleus, ... Their life cycle is broken down into 4 stages: embryo, larva, pupa, adult.[16] The eggs, which are about 0.5 mm long, hatch ... Nuclear division in the early Drosophila embryo happens so quickly, no proper checkpoints exist, so mistakes may be made in ... Each ommatidium contains eight photoreceptor cells (R1-8), support cells, pigment cells, and a cornea. Wild-type flies have ...
"Cell. 172 (1-2): 41-54.e19. doi:10.1016/j.cell.2017.11.033. PMC 5766829. PMID 29249361.. ... G-protein activation/deactivation cycleEdit. Cartoon depicting the Heterotrimeric G-protein activation/deactivation cycle in ... Margeta-Mitrovic M, Jan YN, Jan LY (July 2000). "A trafficking checkpoint controls GABA(B) receptor heterodimerization". Neuron ... "Cell. 166 (4): 907-19. doi:10.1016/j.cell.2016.07.004. PMC 5418658. PMID 27499021.. ...
Eukaryotic cells respond to damaged DNA by stimulating or impairing G1, S, or G2 phases of the cell cycle to initiate DNA ... "Estrogen receptor beta decreases survival of p53-defective cancer cells after DNA damage by impairing G₂/M checkpoint signaling ... the cycle progresses compared to an average cycle. - The ranges denoted Inter-cycle variability are more appropriate to use in ... Estradiol is produced by action of aromatase mainly in the Leydig cells of the mammalian testis, but also by some germ cells ...
For his innovative contributions at the forefront of the field of cell cycle checkpoints and his elucidation of pathways and ... For his discovery that pure phage lambda DNA can infect susceptible bacterial cells and produce progeny, and for the effect of ... For his leading role in developing and applying methods to measure the transmission of genetic information in the cell. ... For his innovative use of molecular and cell biological tools to analyze the genome of an oncogenic virus. ...
Cell Cycle 7 (17): 2720-6. PMID 18758239. doi:10.4161/cc.7.17.6580.. ... "WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Lett. 575 (1-3): 23 ... "Ksp-cadherin is a functional cell-cell adhesion molecule related to LI-cadherin". Exp. Cell Res. 294 (2): 345-55. PMID 15023525 ... Wijnhoven BP, Dinjens WN, Pignatelli M (2000). "E-cadherin-catenin cell-cell adhesion complex and human cancer.". The British ...
cell morphogenesis involved in neuron differentiation. • mitotic cell cycle checkpoint. • regulation of transcription from RNA ... glial cell apoptotic process. • regulation of cohesin loading. • regulation of cell cycle. • neuron maturation. • cell division ... cell cycle arrest. • enucleate erythrocyte differentiation. • neuron differentiation. • regulation of mitotic cell cycle. • ... "Cells Degrade a Novel Inhibitor of Differentiation with E1A-Like Properties upon Exiting the Cell Cycle". Mol. Cell. Biol. 20 ( ...
"Cell Cycle. 7 (16): 2479-84. doi:10.4161/cc.7.16.6479. PMC 2651394. PMID 18719375.. ... DNA damage checkpoint". Genes & Development. 15 (5): 522-34. doi:10.1101/gad.864101. PMC 312651. PMID 11238374.. ... A second cell division produces the ABp and ABa cells from the AB cell, and the EMS and P2 cells from the P1 cell. This ... The resulting daughter cells of the first cell division are called the AB cell (containing PAR-6 and PAR-3) and the P1 cell ( ...
... the ordered sequence of events that occur in a cell in preparation for cell division. The cell cycle is a four-stage process in ... which the cell increases in size, copies its DNA, prepares to divide, and divides. Learn more about the cell cycle and the ... Cell cycle, the ordered sequence of events that occur in a cell in preparation for cell division. The cell cycle is a four- ... Cells use special proteins and checkpoint signaling systems to ensure that the cell cycle progresses properly. Checkpoints at ...
After the cell has split into its two daughter cells, the cell enters G1. DNA repair processes and cell cycle checkpoints have ... Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. Each checkpoint ... Biochemical switches in the cell cycle Cell cycle analysis G2-M DNA damage checkpoint Postreplication checkpoint Meiotic ... known as the cell cycle control system, which monitors and dictates the progression of the cell through the cell cycle. This ...
Areas of interest include gene therapy, cell kinetics, pharmacokinetics, chemotherapy, oncology, developmental biology, wound ... Piotr Widlak, "The DNA Damage-Induced Cell Cycle Checkpoints," Journal of Theoretical Medicine, vol. 2, no. 4, pp. 237-243, ... The DNA Damage-Induced Cell Cycle Checkpoints. Piotr Widlak Department of Experimental and Clinical, Radiobiology, Center of ...
... the spindle checkpoint) to regulate the cell cycle. ... How cells use checkpoints at the end of G1 phase, end of G2 ... How cells use checkpoints at the end of G1 phase, end of G2 phase, and partway through M phase (the spindle checkpoint) to ... Science·Biology·Cell division·Cell cycle regulation, cancer, and stem cells. Cell cycle checkpoints. ... Cell division. Cell cycle regulation, cancer, and stem cells. Cell cycle regulation, cancer, and stem cells. ...
Surveillance mechanisms stop progression throughthe cell cycle at specific checkpoints (at the G1 → S, G2 → M and metaphase → ... Walworth NC (2000) Cellcycle checkpoint kinases: checking in on the cell cycle. Current Opinion in Cell Biology 12: 697-704. ... Checkpoints in the Cell Cycle. Béla Novák, Budapest University of Technology and Economics, Budapest, Hungary Jill C Sible, ... Mammalian checkpoint pathways that block cell cycle progression as a consequence of blocked deoxyribonucleic acid (. DNA. ) ...
Cell cycle checkpoint protein, Rad1 (IPR003011). Short name: Cell_cycle_checkpoint_Rad1 ... A conserved checkpoint pathway mediates DNA damage--induced apoptosis and cell cycle arrest in C. elegans.. Mol. Cell 5 435-43 ... Rad1 is a component of the 9-1-1 cell-cycle checkpoint response complex, which plays a role in checkpoint activation that ... In Caenorhabditis elegans, the cell cycle checkpoint protein RAD1 homologue mrt-2 has a role in genome stability by promoting ...
... repair or spindle assembly to arrest the progress of the cell cycle at one of three checkpoints. Fai … ... cells must ensure that they finish DNA replication, DNA repair and chromosome segregation. They do so by using feedback ... Creative blocks: cell-cycle checkpoints and feedback controls Nature. 1992 Oct 15;359(6396):599-604. doi: 10.1038/359599a0. ... repair or spindle assembly to arrest the progress of the cell cycle at one of three checkpoints. Failures in feedback controls ...
Cell cycle checkpoints are regulatory pathways that control the order and timing of cell cycle transitions and ensure that ... In addition, checkpoints respond to damage by arresting the cell cycle to provide time for repair and by inducing transcription ... Checkpoint pathways have components shared among all eukaryotes, underscoring the conservation of cell cycle regulatory ... Checkpoint loss results in genomic instability and has been implicated in the evolution of normal cells into cancer cells. ...
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... this failure of cell cycle arrest responses in malignant cells can also be exploited therapeutically. Cells in which checkpoint ... Re-expression of p16INK4a in mesothelioma cells results in cell cycle arrest, cell death, tumor suppression and tumor ... Following flavopiridol treatment, nontransformed cells can undergo cell cycle arrest followed by cell death in vitro, and in ... Anticancer drug targets: cell cycle and checkpoint control. Geoffrey I. Shapiro1 and J. Wade Harper2 1Department of Adult ...
cell cycle checkpoint control protein RAD9A isoform 1 [Homo sapiens] cell cycle checkpoint control protein RAD9A isoform 1 [ ... This gene product is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle ... cell cycle checkpoint control protein RAD9A isoform 1 [Homo sapiens]. NCBI Reference Sequence: NP_004575.1 ... Cell Cycle. 2014] The checkpoint clamp protein Rad9 facilitates DNA-end resection and prevents alternative non-homologous end ...
In this report we screened the promoter regions of 16 cell cycle checkpoint genes for DNA variants and assessed the functional ... Since the G1/S transition in the cell cycle is a finely regulated biological process we hypothesized that sequence variations ... D ow nloaded from 2 A substantial number of genes mutated in human cancers encode components of the cell cycle processes. ... In this report we screened the promoter regions of 16 cell cycle checkpoint genes for DNA variants and assessed the functional ...
Control mechanisms enforcing dependency in the cell cycle are here called checkpoints. Elimination of checkpoints may result in ... Checkpoints: controls that ensure the order of cell cycle events Message Subject. (Your Name) has forwarded a page to you from ... The events of the cell cycle of most organisms are ordered into dependent pathways in which the initiation of late events is ... It appears that some checkpoints are eliminated during the early embryonic development of some organisms; this fact may pose ...
Cell cycle checkpoints. Genetics as it applies to evolution, molecular biology, and medical aspects. ... Chapter 17 tells you all about the cell cycle and programmed cell death. Hint: you should something about S-cdk and the ORC. ... Could someone please tell me in detail what happens in the G1/S checkpoint? I hav been looking everywhere with no result. ... have you already searched in Molecular Biology of the Cell bij Alberts et al. ...
IR-induced cell-cycle checkpoint function was also defective, and induction of p21 was attenuated in thymus from Atm-deficient ... Atm selectively regulates distinct p53-dependent cell-cycle checkpoint and apoptotic pathways.. Barlow C1, Brown KD, Deng CX, ... To determine the relationship between Atm and p53, we examined cell-cycle and apoptotic responses in Atm-, p53-(ref. 8) and p21 ... p53 is a multi-functional protein that simultaneously regulates distinct downstream pathways controlling cell-cycle progression ...
3B). Fewer mitotic cells were observed in Cdc25A-siRNA-treated cells relative to control cells. Control cells and cells ... Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints ... Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints ... Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints ...
p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts. M L ... p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts ... p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts ... p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human fibroblasts ...
The Aspergillus nidulans snt Genes Are Required for the Regulation of Septum Formation and Cell Cycle Checkpoints. Peter R. ... The Aspergillus nidulans snt Genes Are Required for the Regulation of Septum Formation and Cell Cycle Checkpoints. Peter R. ... The Aspergillus nidulans snt Genes Are Required for the Regulation of Septum Formation and Cell Cycle Checkpoints. Peter R. ... The Aspergillus nidulans snt Genes Are Required for the Regulation of Septum Formation and Cell Cycle Checkpoints ...
... Nat Genet. 2008 Mar;40(3):356-61. doi: 10.1038 ... that mitochondrial dysfunction activates at least two retrograde signals to specifically enforce a G1-S cell cycle checkpoint. ... we establish that disruption of complex I of the mitochondrial electron transport chain specifically retards the cell cycle ... the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle ...
A conserved checkpoint pathway mediates DNA damage-induced apoptotsis and cell cycle arrest in C. ... MIL induced DNA damage in human hepatocarcinoma cells Tumor cells would undergo cell cycle arrest or apoptotic death ... cells activate checkpoint pathways that lead to =-=(1)-=- DNA repair; (2) a transient cell cycle arrest in order to allow for ... cells activate DNA damage checkpoint pathways that stimu-late DNA repair, lead to a transient cell cycle arrest, and/or elicit ...
cell cycle checkpoint protein RAD17 isoform X4Imported. ,p>Information which has been imported from another database using ... cell cycle checkpoint protein RAD17 isoform X5Imported. Automatic assertion inferred from database entriesi ... tr,A0A2D0PLZ5,A0A2D0PLZ5_ICTPU cell cycle checkpoint protein RAD17 isoform X4 OS=Ictalurus punctatus OX=7998 GN=rad17 PE=3 SV=1 ... Cell cycleARBA annotation. ,p>Information which has been generated by the UniProtKB automatic annotation system, without manual ...
Cells with suppressed expression of Rad51 gene have altered cell cycles and accumulate in the S and G2 phases. Our findings ... Role of human RAD51 recombinase in the cycle checkpoint and survival of a cell. ... However, some cells, e.g., MCF-7 cells, are insensitive to the suppression of Rad51 gene expression. ... Mladenov E., Tsaneva, I., and Anachkova, B., Cell Cycledependent Association of Rad51 with the Nuclear Matrix DNA, Cell Biol., ...
... cell line A549. Flow cytometry analysis showed xanthatin induced cell cycle arrest at G2/M phase. Xanthatin also had pro- ... We conclude that xanthatin displays significant antitumor effects through cell cycle arrest and apoptosis induction in A549 ... which contributed to the cell cycle arrest. Xathatin also increased total p53 protein levels, decreased Bcl-2/Bax ratio and ... In this study, we demonstrated that xanthatin had obvious dose-/time-dependent cytotoxicity against the human non-small-cell ...
... suggesting ALDH1A1-dependent regulation of cell cycle checkpoints and DNA repair networks in ovarian cancer stem-like cells. ... A stable shRNA knockdown model for ALDH1A1 was utilized to determine its effect on cancer stem cell-like properties, cell cycle ... that ovarian cancer cells expressing ALDH1A1 may maintain platinum resistance by altered regulation of cell cycle checkpoint ... We evaluated ALDH+ ovarian cancer stem cell-like properties and their role in platinum resistance. Methods Isogenic ovarian ...
Cell cycle checkpoints are surveillance mechanisms that ensure the ordered progression of events during the cell division cycle ... SWITCHING OFF A CELL CYCLE CHECKPOINT. A model for feedback control of spindle checkpoint activity ... The checkpoint is functional and the APC is repressed, arresting the cell cycle at metaphase. (Right) When all chromosomes have ... It is important that checkpoints function at the correct stage of the cell cycle. For example, during mitosis, the spindle ...
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 ...
Cell Cycle Analysis.. Cell cycle analysis was performed as described previously, whereby cells were harvested, fixed in ethanol ... Analysis of cell cycle checkpoint-regulatory proteins Chk1, Chk2, and Cdc25C. MDA-MB-231 cells were incubated with 10 ng/ml ... We have demonstrated previously that incubation of MDA-MB-231 cells with SN38 arrests cells in different cell cycle phases, ... The Protein Kinase C Inhibitor Gö6976 Is a Potent Inhibitor of DNA Damage-induced S and G2 Cell Cycle Checkpoints Ethan A. Kohn ...
Cell cycle checkpoints constitute regulatory mechanisms that do not allow a new phase of the cell cycle to proceed before the ... Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death. Ragnhild V. Nome, ... The tumor cell defense response to ionizing radiation involves activation of cell cycle checkpoint signaling. Histone ... Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death ...
Evidence for a Connection between the Mismatch Repair System and the G2 Cell Cycle Checkpoint. Mary T. Hawn, Asad Umar, John M. ... Growth kinetics and cell cycle analysis revealed that the growth of 6TG-treated HCT116+chr3 cells was arrested at G2 after ... Evidence for a Connection between the Mismatch Repair System and the G2 Cell Cycle Checkpoint ... Evidence for a Connection between the Mismatch Repair System and the G2 Cell Cycle Checkpoint ...
Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death. Ragnhild V. Nome, ... Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death ... Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death ... Cell cycle checkpoint signaling involved in histone deacetylase inhibition and radiation-induced cell death ...
  • Cell cycle checkpoints are control mechanisms in the eukaryotic cell cycle which ensure its proper progression. (
  • Each checkpoint serves as a potential termination point along the cell cycle, during which the conditions of the cell are assessed, with progression through the various phases of the cell cycle occurring only when favorable conditions are met. (
  • Progression through these checkpoints is largely determined by the activation of cyclin-dependent kinases by regulatory protein subunits called cyclins, different forms of which are produced at each stage of the cell cycle to control the specific events that occur therein. (
  • 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. (
  • Those complexes, in turn, activate different downstream targets to promote or prevent cell cycle progression. (
  • The three pocket proteins are Retinoblastoma (Rb), p107, and p130, which bind to the E2F transcription factors to prevent progression past the G1 checkpoint. (
  • Surveillance mechanisms stop progression through the cell cycle at specific checkpoints (at the G1 → S, G2 → M and metaphase → anaphase transitions) if certain crucial requirements have not been met. (
  • Mammalian checkpoint pathways that block cell cycle progression as a consequence of blocked deoxyribonucleic acid ( DNA ) replication and DNA damage. (
  • Rad1 is a component of the 9-1-1 cell-cycle checkpoint response complex, which plays a role in checkpoint activation that permits DNA-repair pathways to prevent cell cycle progression in response to DNA damage and replication stress [ PMID: 9311982 , PMID: 21978893 ]. (
  • Central players are the cyclin-dependent kinases (cdks), which govern the initiation, progression, and completion of cell cycle events. (
  • The crucial role of the cdks has prompted great interest in the development of specific kinase inhibitors that would be expected to block cell cycle progression and induce growth arrest. (
  • Unbridled cell cycle progression in the presence of such damage is usually lethal, which may explain the selective sensitivity of some cancer cells to DNA-damaging treatments. (
  • p53 is a multi-functional protein that simultaneously regulates distinct downstream pathways controlling cell-cycle progression and apoptosis. (
  • These findings indicate that Chk1 directly phosphorylates Cdc25A during an unperturbed cell cycle, and that phosphorylation of Cdc25A by Chk1 is required for cells to delay cell cycle progression in response to double-strand DNA breaks. (
  • sntA1 and sntB1 mutants have different effects on cell cycle progression in the sepB3 background. (
  • Thus, our results indicate that the mitochondrion can use AMP and ROS at sublethal concentrations as independent signaling molecules to modulate cell cycle progression. (
  • The utility of this system was revealed by the finding that upon treatment with genotoxic agents, premeiotic C. elegans germ cells transiently halt cell cycle progression, whereas meiotic prophase germ cells in the late pachytene stage readily undergo apoptosis. (
  • Cell cycle checkpoints are surveillance mechanisms that ensure the ordered progression of events during the cell division cycle. (
  • Checkpoints prevent progression to the next stage of the cycle until the upstream event has been completed. (
  • Further, the genetic materials required to sustain cleavage cycles are preloaded during oogenesis, aiding efficient cell cycle progression. (
  • In response to DNA damage, cells arrest progression through the cell cycle at either G 1 , S, or G 2 . (
  • These checkpoints arrest cell cycle progression to allow time for repair of DNA lesions before genome duplication in S phase and chromosomal segregation in mitosis and thereby protect against the propagation of progeny cells containing damaged or mutated DNA. (
  • A time-course analysis of cell-cycle progression revealed that MPT0L184 treatment elicited an early onset of mitosis but prevented the division of cells with duplicated chromosomes. (
  • Ataxia telangiectasia-mutated and Rad3-related (ATR) plays a central role in cell-cycle regulation, transmitting DNA damage signals to downstream effectors of cell-cycle progression. (
  • The Schizosaccharomyces pombe Rad3 homologs (ataxia telangiectasia-mutated and Rad3-related [ATR] and ataxia telangiectasia-mutated [ATM] in mammals, Mec1 in S. cerevisiae ) are essential regulators of cell-cycle checkpoints, sensing DNA damage and/or single-stranded DNA and activating downstream effectors of cell-cycle progression and DNA repair. (
  • A role for MLH1 in G2-M cell cycle checkpoint control, without alteration in G1, after IR was also suggested by similar S-phase progression between irradiated MLH1-deficient and MLH1-proficient human or murine cells. (
  • The research team, led by Prabhat Goswami, Ph.D., UI assistant professor of radiation oncology in the Free Radical and Radiation Biology Graduate Program, will test the idea that reactive oxygen species (ROS) produced by cells control the progression from the G1 phase of the cell cycle to the S phase, in which DNA is synthesized. (
  • These results suggest that the redox environment regulates cell cycle progression, and that redox control of the cell cycle could be different in normal cell and in cancer cells. (
  • Normal cells with redox-sensitive checkpoints would halt cell cycle progression in response to agents that disturb the cellular redox state. (
  • A clearer picture of the role that intracellular redox states play in cell cycle progression should lead to a better understanding of normal and aberrant cellular proliferation. (
  • Cell cycle checkpoints exist to protect the cells by arresting cell cycle progression in response to DNA damage or replication stress. (
  • We recently recognized a previously uncharacterized linkage between the replication stress response and the SCF ubiquitin-proteasome pathway (Kile and Koepp 2010) a system that is better known for its part in protein turnover during cell-cycle progression (Ang and Harper 2005). (
  • A brief exposure to this compound stops fork progression at or near replication origin and renders the forks incompetent to resume replication despite the presence of a functional checkpoint. (
  • The coupling of cyclin dependent kinases (CDKs) to an intrinsically oscillating network of transcription factors has been proposed to control progression through the cell cycle in budding yeast, Saccharomyces cerevisiae . (
  • The transcription network regulates the temporal expression of many genes, including cyclins, and drives cell-cycle progression, in part, by generating successive waves of distinct CDK activities that trigger the ordered program of cell-cycle events. (
  • Network oscillations continue autonomously in mutant cells arrested by depletion of CDK activities, suggesting the oscillator can be uncoupled from cell-cycle progression. (
  • It is not clear what mechanisms, if any, ensure that the network oscillator is restrained when progression in normal cells is delayed or arrested. (
  • Further, we demonstrate that the DNA replication checkpoint effector protein, Rad53, acts to arrest a portion of transcript oscillations in addition to its role in halting cell-cycle progression. (
  • Our findings indicate that checkpoint mechanisms, likely via phosphorylation of network transcription factors, maintain coupling of the network oscillator to progression during cell-cycle arrest. (
  • Is there a mechanism that ensures the transcription network oscillator is restrained when cell-cycle progression has been slowed or arrested, or does the network oscillator continue to free-run and get re-entrained at a later time? (
  • In budding yeast, physiological perturbations that inhibit cell-cycle progression do so through checkpoints whose primary effect is thought to be maintenance of high mitotic CDK activity. (
  • Therefore, we sought to test the hypothesis that mitotic CDKs function not only as effectors of the network oscillator, but also act to stall the transcription network oscillator when cell-cycle progression is delayed. (
  • Cell cycle progression and micronucleus formation (MN) were used as end points. (
  • Thus, these kinases relay and amplify the damage signal and effector proteins that control cell cycle progression, chromatin restructuring, and DNA repair. (
  • In conclusion, a conflict in cell cycle progression or DNA damage can lead to mitotic catastrophe, provided that the checkpoint kinase Chk2 is inhibited. (
  • Checkpoint controls are regulatory pathways that inhibit cell cycle progression in cells that have not faithfully completed a prior step in the cell cycle. (
  • In eukaryotic cells, there are evolutionarily conserved pathways that sense and respond to various types of cellular stress via a series of checkpoints that delay the progression to the next phase of the cell cycle. (
  • The mechanical error in attachment must somehow be linked to the chemical regulation of cell cycle progression. (
  • Abstract] Cell synchronization is widely used in studying mechanisms involves in regulation of cell cycle progression. (
  • Besides checkpoint activation, Rad17 may also serve as a sensor of DNA replication progression, and may be involved in homologous recombination [ PMID: 15297881 ]. (
  • This gene encodes a component of a heterotrimeric cell cycle checkpoint complex, known as the 9-1-1 complex, that is activated to stop cell cycle progression in response to DNA damage or incomplete DNA replication. (
  • Thus, at least in the scenario studied, in which yeast bear mutations in the genes encoding the Smc5 and Smc6 proteins (which function as a heterodimer in DNA repair), the delayed replication of rDNA did not trigger a checkpoint that blocks progression of the cells into mitosis. (
  • The molecular pathways linking DNA-damage checkpoint proteins to cell-cycle progression remain largely unresolved. (
  • 2007) reported in this issue suggest that tRNA trafficking and the transcription factor Gcn4 are key intermediates in the process by which yeast cells detect DNA damage and delay cell-cycle progression at the G1 to S phase transition. (
  • To avoid transmission of altered genome to daughter cells, elaborate checkpoint pathways have evolved to arrest cell cycle progression and promote repair or, in case of unrepairable damage, stimulate cell death. (
  • Such defects very likely contribute to neoplastic transformation and progression by coupling genetic instability with resistance to apoptotic cell death. (
  • The overall cellular response to damaged DNA, known as DNA damage response (DDR), is composed of sensor proteins that detect and signal DNA damage to downstream effectors that, in turn, arrest cell cycle progression and promote repair. (
  • The mitotic checkpoint is an external monitoring system that by itself is not required for mitotic progression but detects the presence of chromosomes that are not attached to the mitotic spindle via their kinetochores and, in their presence, initiates a cascade that prohibits activation of the APC and thus chromosome separation and exit from mitosis. (
  • Prior studies showed that p53-defective cells that arrest in S and G 2 , but not p53 wild-type cells , can be sensitized to DNA damage by the checkpoint inhibitor caffeine , which causes premature cell cycle progression and lethal mitosis . (
  • UCN-01 induced S and G 2 progression in the p53-defective MDA-MB-231 cells at low nanomolar concentrations , whereas higher concentrations caused lethal mitosis without cell cycle progression , likely due to inhibition of C-TAK 1 . (
  • At each checkpoint, the progression to the next cell cycle stage can be halted until conditions are more favorable. (
  • Under this cascade, failure to synapse will maintain the gene expression from sex chromosomes and some products may inhibit cell cycle progression. (
  • CHEK2 regulates cell cycle progression and spindle assembly during mouse oocyte maturation and early embryo development. (
  • Likewise, a checkpoint during mitosis ensures that the cell's spindle fibres are properly aligned in metaphase before the chromosomes are separated in anaphase. (
  • and the M (mitosis) phase, during which the duplicated chromosomes (known as the sister chromatids) separate into two daughter nuclei, and the cell divides into two daughter cells, each with a full copy of DNA. (
  • When checkpoint arrest control is compromised, initiation of S phase or mitosis occurs despite cellular damage, and the ensuing genetic instability may lead to the eventual emergence of a malignant clone. (
  • For example, during mitosis, the spindle checkpoint monitors chromosome alignment on the mitotic spindle. (
  • Inhibition of damage-induced checkpoints by pharmacological means leads to abrogation of cell cycle arrest and subsequent lethal mitosis, thereby sensitizing cells to DNA-damaging agents. (
  • In the normal dividing cell, the transition from the G 2 phase to mitosis is inhibited through phosphorylations of the Cdc2 kinase of the Cdc2/cyclin B complex. (
  • Therefore, cells that are in the beginning bigger or smaller than the mean after mitosis tend to go back to the mean size as time passes. (
  • During the normal cell cycle, bud formation is temporally coincident with DNA replication and spindle assembly, and the nucleus divides along the mother-bud axis in mitosis. (
  • In the G2 phase, the cell checks that DNA synthesis and repair are complete, and that the cell has reached a critical size before mitosis is initiated. (
  • The cell cycle consists of four distinct phases: G1 (Gap1) phase, S phase (synthesis), G2 (Gap2) phase (collectively known as interphase) and M phase (mitosis). (
  • M (mitosis) phase is itself composed of two tightly coupled processes: mitosis, in which the cell's chromosomes are divided between the two daughter cells, and cytokinesis, in which the cell's cytoplasm divides in half forming distinct cells. (
  • After S phase or replication cell then enters the G2 phase, which lasts until the cell enters mitosis. (
  • Inhibition of protein synthesis during G2 phase prevents the cell from undergoing mitosis. (
  • After the mitosis stage the cell may continue with the cell cycle and enter the G1 phase or it may opt out of the cell cycle and diverge into the G0 phase. (
  • Destruction of anaphase disintegrates the MPF and inturn pushes the cell out of mitosis, allowing the new daughter cells to enter G1. (
  • The cell cycle consists of four phases, G1 (GAP 1), S (synthesis), G2 (GAP 2) and M (mitosis). (
  • Amit Dravid Thesis submitted to the Faculty of the Cell-Cycle Checkpoints: Keeping mitosis in check. (
  • cells lacking g2 check point are radiosensitive as they can not repair damaged chromosome before enteringm normal Cell-Cycle Checkpoints: Keeping mitosis in check. (
  • Cell cycle checkpoints are times during the cell cycle in which the cell checks to see whether it is ready to proceed with mitosis or cell division. (
  • In M phase, the chromosomes need to be properly aligned and the spindles need to be oriented towards the daughter cell (M-metaphase checkpoint), and the cell should be correctly divided into two, before the end of mitosis (M-telophase checkpoint). (
  • Cells use biochemical signaling mechanisms known as checkpoints to monitor the status of the cell so that cell division occurs only when conditions allow for successful mitosis. (
  • Cell division in mitosis and meiosis is governed by evolutionary highly conserved protein kinases and phosphatases, controlling the timely execution of key events such as nuclear envelope breakdown, spindle assembly, chromosome attachment to the spindle and chromosome segregation, and cell cycle exit. (
  • In mitosis, the spindle assembly checkpoint (SAC) controls the proper attachment to and alignment of chromosomes on the spindle. (
  • ATR and Chk1 also trigger the G2/M checkpoint, which prevents cells with damaged DNA from entering mitosis. (
  • The CDK-cyclin complex that is required for entry into mitosis is CDK1-cyclin B, and cells are driven from G2 into mitosis by its sudden activation. (
  • Then, during mitosis and cytokinesis, the cell divides its nuclear and cytoplasmic materials, respectively. (
  • Here, the cell ensures that all of the DNA has been replicated and is not damaged before entering mitosis. (
  • Although initially named a "checkpoint" because of its activation in response to spindle damage in yeast, in mammals it is an essential mechanism that serves to control advance to anaphase during every mitosis. (
  • AKAP95-depleted HeLa cells show micronuclei formed from lagging chromosomes at mitosis. (
  • Kinetochore (KT) localization of mitotic checkpoint proteins is essential for their function during mitosis. (
  • Uncoupling of S phase and mitosis induced by anticancer agents in cells lacking p21. (
  • Generally speaking, the cell cycle regulation of meiosis is similar to that of mitosis. (
  • The first major regulatory transition occurs in late G1, when the start of meiotic cycle is activated by Ime1 instead of Cln3/Cdk1 in mitosis. (
  • Checkpoint pathways (dashed lines) modulate the activities of the accelerators and brakes. (
  • Checkpoint pathways that block mitotic transitions as a consequence of spindle damage. (
  • Gardner RD and Burke DJ (2000) The spindle checkpoint: two transitions, two pathways. (
  • Nurse P (1997) Checkpoint pathways come of age. (
  • Rhind N and Russell P (2000) Chk1 and Cds1: linchpins of the DNA damage and replication checkpoint pathways. (
  • Cell cycle checkpoints are regulatory pathways that control the order and timing of cell cycle transitions and ensure that critical events such as DNA replication and chromosome segregation are completed with high fidelity. (
  • Recent advances have revealed signal transduction pathways that transmit checkpoint signals in response to DNA damage, replication blocks, and spindle damage. (
  • Checkpoint pathways have components shared among all eukaryotes, underscoring the conservation of cell cycle regulatory machinery. (
  • The events of the cell cycle of most organisms are ordered into dependent pathways in which the initiation of late events is dependent on the completion of early events. (
  • Atm selectively regulates distinct p53-dependent cell-cycle checkpoint and apoptotic pathways. (
  • Our results support a model in which upstream effectors such as Atm selectively activate p53 to regulate specific downstream pathways, providing a mechanism for controlling distinct cell-cycle and apoptotic responses. (
  • In response to genotoxic insults, cells activate DNA damage checkpoint pathways that stimu-late DNA repair, lead to a transient cell cycle arrest, and/or elicit programmed cell death (apoptosis) of affected cells. (
  • Genetics- and genomics-based approaches that have demonstrated roles for conserved checkpoint proteins have also begun to uncover novel components of these response pathways. (
  • In the face of DNA damage, the genomic integrity of mammalian cells is maintained by activating signaling pathways called DNA damage checkpoints. (
  • Cell-cycle development is monitored by checkpoint pathways that pause the cell routine when tension arises to threaten the integrity from the genome. (
  • Pierisin-1 treatment of HeLa cells was found to induce an intra-S-phase arrest through both ataxia telangiectasia mutated (ATM) and Rad3-related (ATR) and ATM pathways, and ATR pathway also contributes to a G 2 -M-phase delay. (
  • The checkpoint 2 gene (CHEK2) is an important transducer in DNA damage signaling pathways in response to injury, and therefore, CHEK2 variants may affect susceptibility to kidney disease.MethodsWe used tag-single-nucleotide polymorphisms (tag-SNPs) to evaluate the association of the CHEK2 with kidney function (estimated glomerular filtration rate, eGFR) in 1,549 African-American and 1,423 white Hypertension Genetic Epidemiology Network (HyperGEN) participants. (
  • point pathways cause cell cycle arrest. (
  • We conducted a genome-wide RNAi (RNA interference) screen in Drosophila cells to identify previously unknown genes and pathways required for the G₂-M checkpoint induced by DNA double-strand breaks (DSBs). (
  • Checkpoint kinase (Chk)1 is an evolutionarily conserved protein kinase that was first identified in fission yeast as an essential component of the DNA damage checkpoint. (
  • Checkpoint kinase (Chk)1 was first identified in fission yeast as an essential component of the DNA damage checkpoint but was later shown to also function in the DNA replication checkpoint ( 1-7 ). (
  • Instead, using immunostaining to examine checkpoint signaling, I show that cleavage-stage embryos cannot activate the checkpoint protein Chk1 kinase after damage induction. (
  • Considering the difficulties with UCN-01, we have sought checkpoint inhibitors that abrogate damage-induced arrest but lack these undesirable additional properties ( i.e. , plasma binding and nonspecific kinase inhibition). (
  • After radiation exposure, the G 2 -M phase accumulation and the preceding repression of the G 2 phase regulatory factors Polo-like kinase-1 and cyclin B1 required intact G 2 checkpoint signaling through the checkpoint kinase CHK1, whereas the similar phenotypic changes observed with HDAC inhibition did not. (
  • DNA damage-induced G 2 checkpoint signaling, initiated by the ATM kinase and communicated through downstream mediator proteins like p53 and the checkpoint kinase CHK1 ( 6 , 9 ), will ultimately disrupt the interaction of Cdc25C with Cdc2 ( 6 ). (
  • The checkpoint kinase CHK2 is the mammalian homologue of yeast Cds1/Rad53. (
  • In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates CHK2, which in turn directly phosphorylates and activates p53. (
  • Storgaard Sørensen, C et al: The cell cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. (
  • In response to DNA damage, checkpoint signals are evoked primarily in the form of kinase-mediated protein phosphorylation to arrest cells in the G 1 -S, S, and G 2 -M phases and allows time for repair to take place ( 13 ). (
  • Fusion between nonsynchronized cells leads to the formation of heterokarya which transiently activate Cyclin-dependent kinase 1 (Cdk1)/cyclin B1 and enter the prophase of the cell cycle, where they arrest due to a loss of Cdk1/cyclin B1 activity, activate p53, disorganize centrosomes, and undergo apoptosis. (
  • regulation of Cdk1/cyclin B is secondary to the activation of the DNA structure checkpoint kinase Chk2. (
  • Early studies in lower Eukaryotes have defined a role for the members of the NimA related kinase (Nek) family of protein kinases in cell cycle control. (
  • Here, we aim to provide a comprehensive account of our understanding of Nek kinase biology and their involvement in cell cycle, checkpoint control and cancer. (
  • The delay occurs after DNA replication and spindle assembly, and results from delayed activation of the master cell cycle regulatory kinase, Cdc28. (
  • Inactivation of the RAD53 kinase is required to recover from checkpoint-mediated cell cycle arrest in S. cerevisiae. (
  • 3ZTX: Aurora kinase selective inhibitors identified using a Taxol-induced checkpoint sensitivity screen. (
  • The members of the Aurora kinase family play critical roles in the regulation of the cell cycle and mitotic spindle assembly and have been intensively investigated as potential targets for a new class of anticancer drugs. (
  • Two cell cycle kinase complexes, CDK4/6-Cyclin D and CDK2- Cyclin E, work together to relieve the inhibition of dynamic transcriptional complexes containing retinoblastoma protein (Rb) and E2F. (
  • The checkpoint pathway transmits signals from the sites of DNA damage to the cell cycle machinery through the evolutionarily conserved ATM (ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related) kinase cascades. (
  • In particular, the Ataxia Telangiectasia Mutated (ATM) kinase is activated by DNA double strand breaks (DSBs) and triggers the G1 checkpoint by phosphorylating and activating the Checkpoint Kinase 2 (Chk2) [ 11 ]. (
  • Chk2 inhibits Cdc25A, a phosphatase that removes inhibitory phosphorylation of the cyclin A/Cyclin-dependent kinase (Cdk)2 and cyclin E/Cdk2 complexes, preventing cells from proceeding into S phase [ 12 ]. (
  • It also directly binds to BubR1, a kinetochore-associated kinase implicated in the mitotic checkpoint, the major cell cycle control pathway in which unattached kinetochores prevent anaphase onset. (
  • Thus, CENP-E is required for enhancing recruitment of its binding partner BubR1 to each unattached kinetochore and for stimulating BubR1 kinase activity, implicating it as an essential amplifier of a basal mitotic checkpoint signal. (
  • During meiotic recombination in human and mouse, CHEK1 protein kinase is important for integrating DNA damage repair with cell cycle arrest. (
  • A conserved checkpoint pathway mediates DNA damage--induced apoptosis and cell cycle arrest in C. elegans. (
  • This pathway involves p53, as Atm-deficient cell lines and mice are defective in p53 induction after IR. (
  • We provide evidence that Chk1 directly regulates Cdc25A throughout an unperturbed cell cycle, and that the integrity of the Chk1/Cdc25A regulatory pathway is essential for cells to respond appropriately to ionizing radiation. (
  • Citation Query A conserved checkpoint pathway mediates DNA damage-induced apoptotsis and cell cycle arrest in C. (
  • Zhang L, Ruan J, Yan L, Li W, Wu Y, Tao L, Zhang F, Zheng S, Wang A, Lu Y. Xanthatin Induces Cell Cycle Arrest at G2/M Checkpoint and Apoptosis via Disrupting NF-κB Pathway in A549 Non-Small-Cell Lung Cancer Cells. (
  • mRNA arrays of cells treated with miR-494, followed by pathway analysis, suggested that miR-494 impacts cell cycle regulation. (
  • ENA also inhibits DNA synthesis in mammalian cells leading to the activa tion of ATM/ ATR pathway and the induction of apoptosis in a p53 independent manner. (
  • The role of the p38 MAPK pathway in the cell differentiation, growth inhibition and apoptosis is well established and has been previously reviewed [ 11 , 12 ]. (
  • The focus of this review is on the less characterized functions of the p38 MAPK pathway, such as its role in the regulation of cell cycle checkpoints and cell survival. (
  • The inhibition of the DNA damage response (DDR) pathway in the treatment of cancers has recently reached an exciting stage with several cell cycle checkpoint inhibitors that are now being tested in several clinical trials in cancer patients. (
  • This review aims to summarize the most recent data found on the biological mechanisms of the response to DNA damages highlighting the role of the different elements of the DDR pathway in normal and cancer cells and focusing on the main genetic alteration or aberrant gene expression that has been found on acute and chronic leukemias. (
  • Molecular and Biochemical Aspects of the PD-1 Checkpoint Pathway. (
  • The DNA damage checkpoint, the first pathway known to be activated in response to DNA damage, is a mechanism by which the cell cycle is temporarily arrested to allow DNA repair. (
  • Our results provide insight into the diverse mechanisms that link DNA damage and the checkpoint signaling pathway. (
  • However, even when satisfied, the checkpoint pathway continues to survey for unattached kinetochores, which, should they arise, readily re-impose the block. (
  • rather , the S phase checkpoint functions through the Chk1-Cdc25A-cyclin E/Cdk2 pathway . (
  • These DNA breaks must be repaired before metaphase I. and these DSBs must be repaired before metaphase I. The cell monitor these DSBs via ATM pathway, in which Cdc25 is suppressed when DSB lesion is detected. (
  • This pathway is the same as classical DNA damage response and is the part we know the best in meiotic recombination checkpoint. (
  • The DSB-independent pathway was proposed when people studied spo11 mutant cells in some species and found that these Spo11 cells could not process to metaphase I even in the absence of DSB. (
  • The proteins that play a role in stimulating cell division can be classified into four groups- growth factors , growth factor receptors , signal transducers, and nuclear regulatory proteins ( transcription factors ). (
  • Cells use special proteins and checkpoint signaling systems to ensure that the cell cycle progresses properly. (
  • However, the cell cycle and its checkpoint systems can be sabotaged by defective proteins or genes that cause malignant transformation of the cell, which can lead to cancer . (
  • The main mechanism of action of the cell cycle checkpoints is through the regulation of the activities of a family of protein kinases known as the cyclin-dependent kinases (CDKs), which bind to different classes of regulator proteins known as cyclins, with specific cyclin-CDK complexes being formed and activated at different phases of the cell cycle. (
  • The E2F gene family is a group of transcription factors that target many genes that are important for control of the cell cycle, including cyclins, CDKs, checkpoint regulators, and DNA repair proteins. (
  • As malignant cells evolve, both genetic and epigenetic mechanisms commonly affect the expression of cell cycle regulatory proteins, causing overexpression of cyclins and loss of expression of cdk inhibitors. (
  • In humans, fission yeast, and Xe , Chk1 has been proposed to regulate the G 2 checkpoint by phosphorylating the Cdc25C protein phosphatase on residue(s) that facilitate the binding of 14-3-3 proteins ( 5 , 15-18 ). (
  • 2000-=-). It is tempting to speculate that the metazoan proteins that share homology with Dot1 (Figure 1) have roles in heterochromatin assembly, telomere metabolism, meiotic checkpoint control, and/or cellu. (
  • Moreover, both cell cycle arrest and pachytene apoptosis responses depend on conserved DNA damage check-point proteins. (
  • Analysis of proteins that regulate cell cycle arrest suggested that both drugs inhibit the checkpoint kinases Chk1 and/or Chk2. (
  • Histone deacetylase (HDAC) inhibitors, agents that cause hyperacetylation of histone proteins and thereby aberrations in the chromatin structure, may also override the DNA damage defense response and facilitate the radiation-induced mitotic cell death. (
  • Checkpoint regulatory proteins in MA-11 cells after exposure to ionizing radiation ( IR ) or the HDAC inhibitor TSA. (
  • 000114857 001__ 114857 000114857 005__ 20181203021031.0 000114857 037__ $$aARTICLE 000114857 245__ $$aA superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins 000114857 269__ $$a1997 000114857 260__ $$c1997 000114857 336__ $$aJournal Articles 000114857 500__ $$aEuropean Molecular Biology Laboratory, Heidelberg, Germany. (
  • 000114857 520__ $$aComputer analysis of a conserved domain, BRCT, first described at the carboxyl terminus of the breast cancer protein BRCA1, a p53 binding protein (53BP1), and the yeast cell cycle checkpoint protein RAD9 revealed a large superfamily of domains that occur predominantly in proteins involved in cell cycle checkpoint functions responsive to DNA damage. (
  • Despite the functional diversity of all these proteins, participation in DNA damage-responsive checkpoints appears to be a unifying theme. (
  • It has been shown that the interaction between the checkpoint proteins Rad9A and TopBP1 is a crucial upstream event required for the ATR-dependent checkpoint response to DNA damage, which can be activated throughout different points in the cell cycle. (
  • BiFC signals could be detected in cells containing the BiFC fusion proteins of Rad9A and TopBP1 using confocal microscopy and flow cytometry techniques. (
  • The BiFC assay employed in this project must be further optimized to effectively study the interaction between Rad9A and TopBP1, as well as other checkpoint proteins. (
  • However, this study has given us great insight into the implementation of this new BiFC technique for studying protein interactions in the context of cell cycle proteins, and the knowledge gained from this study will be invaluable for future work. (
  • In this study, we analyzed cell cycle regulation of plant cell, especially focusing on the chromosome check point proteins. (
  • Pierisin-1 is an ADP-ribosylating toxin targeting a DNA rather than proteins ( 6 ), and the protein consists of a NH 2 -terminal ADP-ribosyltransferase enzymatic domain, which catalyzes the transfer of ADP-ribose moieties from NAD to guanine residues of DNA, and a COOH-terminal receptor-binding domain, which is responsible for incorporation into cells by binding to glycosphingolipid receptors ( 5 , 7 , 8 ). (
  • Background: Recent experimental evidence suggests that DNA damage and cell cycle regulatory proteins are involved in kidney injury and apoptosis. (
  • One of them, based on palbociclib, potently initiates degradation of these CDK proteins, and suppresses phosphorylation of retinoblastoma protein (Rb) leading to cell cycle arrest. (
  • Cell cycle regulators are group of proteins and enzymes that interact with each other in varying concentrations deciding the fate of cell cycle. (
  • Cyclins work by activating and inactivating target proteins inside the cell, which help in the events to occur for the successfull completion of a cell cycle. (
  • These functional enzymes(cdks) then modify the target proteins in the cell to perform their specific set of functions. (
  • It is a very good example of how cyclins and cdks work together for a cellcycle transition.MPF complexes add phosphate groups to different targeted proteins in the cell. (
  • The RAD1 is loaded to damaged sites where it serves as a platform for the selective recruitment of checkpoint and repair proteins. (
  • The cytoplasm also contains proteins that control the replication of DNA in bacterial cells. (
  • Our large-scale analysis provided a systems-level view of the G₂-M checkpoint and revealed the coordinated actions of particular classes of proteins, which include those involved in DNA repair, DNA replication, cell cycle control, chromatin regulation, and RNA processing. (
  • Here, we analyse how the kinetochore localization of the Drosophila spindle checkpoint proteins Bub1, Mad2, Bub3 and BubR1, behave in response to alterations in microtubule binding or tension. (
  • To study the effect of tension we analysed the kinetochore localization of spindle checkpoint proteins in relation to tension-sensitive kinetochore phosphorylation recognised by the 3F3/2 antibody. (
  • Altogether, our results suggest that spindle checkpoint proteins sense distinct aspects of kinetochore interaction with the spindle, with Mad2 and Bub1 monitoring microtubule occupancy while BubR1 and Bub3 monitor tension across attached kinetochores. (
  • Analyses of mutants, antibody microinjection in tissue culture cells and expression of truncated proteins with a dominant negative phenotype, have shown that inhibition of a single protein inactivates the checkpoint (reviewed by Amon, 1999 ), allowing for sister chromatid separation in the absence of microtubules. (
  • The RZZ complex (Roughdeal, ZesteWhite10, and Zwilch) subunits are essential mitotic checkpoint proteins originally identified in flies and are conserved in metazoans ( Karess, 2005 ). (
  • For example, mutations in a protein called p53 , which normally detects abnormalities in DNA at the G1 checkpoint, can enable cancer-causing mutations to bypass this checkpoint and allow the cell to escape apoptosis. (
  • In Caenorhabditis elegans, the cell cycle checkpoint protein RAD1 homologue mrt-2 has a role in genome stability by promoting DNA double strand break-induced cell cycle arrest and apoptosis, and is required for maintaining telomere length and germline immortality [ PMID: 10882129 , PMID: 10646593 , PMID: 16951081 ]. (
  • The novel DNA damage checkpoint protein ddc1p is phosphorylated periodically during the cell cycle and in response to DNA damage in budding yeast. (
  • MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans. (
  • The checkpoint clamp protein Rad9 facilitates DNA-end resection and prevents alternative non-homologous end joining. (
  • Checkpoint protein Rad9 plays an important role in nucleotide excision repair. (
  • In addition, loss of Chk1 resulted in the accumulation of a hypophosphorylated form of the Cdc25A protein phosphatase, and Chk1-deficient cells failed to degrade Cdc25A after IR. (
  • In addition, human Chk1 has been proposed to regulate the stability of the Cdc25A protein phosphatase in UV-damaged cells ( 19 ). (
  • MPS1, an essential component of the spindle checkpoint, was found to be a cell cycle regulated protein. (
  • MPS1 protein abundance decreases after metaphase, at the same time the checkpoint is inactivated, implicating MPS1 stability in the regulation of checkpoint activity. (
  • Overexpressing the protein after metaphase reactivated the spindle checkpoint, suggesting that decreased MPS1 levels have a role in checkpoint inactivation. (
  • The tumor suppressor protein p53 is the primary regulator of the G 1 checkpoint ( 7 ). (
  • Essentially, in tumor cells with intact p53 function, DNA damage leads to rapid p53 stabilization by posttranslational protein modifications as well as induction of the G 1 phase inhibitor p21 ( 7 ). (
  • HDAC inhibition by TSA in MA-11 cells-histone acetylation and poly(ADP-ribose) polymerase protein status. (
  • Bottom, included is a protein extract from MA-11 cells treated (+) with 10 ng/mL of a Pseudomonas exotoxin A-containing immunotoxin ( IT ), used as positive control for poly(ADP-ribose) polymerase cleavage ( 21 ). (
  • The cells were treated (+) with ionizing radiation (8.0 Gy) or TSA (300 nmol/L), or left untreated (−), and protein expression levels of Plk1, p21, p53, and acetylated histone H4 ( acetyl-H4 ) after 0 to 24 hours were determined by Western blot analysis of cell extracts. (
  • Defective expression of the DNA mismatch repair protein, MLH1, alters G2-M cell cycle checkpoint arrest following ionizing radiation. (
  • A role for the Mut L homologue-1 (MLH1) protein, a necessary component of DNA mismatch repair (MMR), in G2-M cell cycle checkpoint arrest after 6-thioguanine (6-TG) exposure was suggested previously. (
  • Interestingly, an enhanced p53 protein induction response was observed in HCT116 3-6 (MLH1+) compared with HCT116 (MLH1-) cells after IR or 6-TG. (
  • Retroviral vector-mediated expression of the E6 protein did not, however, affect the enhanced G2-M cell cycle arrest observed in HCT116 3-6 compared with MLH1-deficient HCT116 cells. (
  • We also show that human MLH1 and MSH2 steady-state protein levels did not vary with damage or cell cycle changes caused by IR or 6-TG. (
  • MLH1-mediated G2-M cell cycle delay (caused by either MMR proofreading of DNA lesions or by a direct function of the MLH1 protein in cell cycle arrest) may be important for DNA damage detection and repair prior to chromosome segregation to eliminate carcinogenic lesions (possibly brought on by misrepair) in daughter cells. (
  • The Bimolecular Fluorescence Complementation (BiFC) technique has recently emerged as a simple and effective tool for analyzing protein-protein interactions in live cell cultures. (
  • Interestingly we found that the proteolysis of the F-box protein Dia2 is definitely regulated from the S-phase checkpoint. (
  • Next, we substitute the amiRNA target sequence of the checkpoint protein encoding gene to make it insensitive to amiRNA, then transformed into the knock-down line. (
  • We propose that the kinetochore protein dephosphorylation caused by tension is the all clear signal to the checkpoint. (
  • But although cyclin-dependent protein kinases (CDKs) are known to trigger the major events of the cell cycle, the precise mechanisms of the checkpoint controls are still uncertain. (
  • This entry represents checkpoint protein Rad24 from budding yeasts and its homologue, Rad17 from other organisms. (
  • The checkpoint protein Rad24 of Saccharomyces cerevisiae is involved in processing double-strand break ends and in recombination partner choice. (
  • Knockdown of , a subunit of the Myb-MuvB transcription factor, or β, a gene involved in protein folding and trafficking, resulted in a switch from cell proliferation to an endoreplication growth program through which wing tissue grew by an increase in cell size (hypertrophy). (
  • The signaling cascade leading to checkpoint arrest depends on several protein kinases that are conserved from yeast to man. (
  • Our data show a novel role of lipidation in targeting a checkpoint protein to KTs through protein-protein interaction. (
  • If DNA damage or abnormalities in spindle formation are detected at these checkpoints, the cell is forced to undergo programmed cell death, or apoptosis . (
  • For example, damage to DNA or the spindle apparatus normally triggers cell cycle arrest or apoptosis, depending on the degree of damage and the cellular context. (
  • DNA damage-induced cell death requires key components of the evolutionarily conserved apoptosis machinery. (
  • We conclude that xanthatin displays significant antitumor effects through cell cycle arrest and apoptosis induction in A549 cells. (
  • Cell phone routine analyses suggest M-VCR-R is considered the most powerful mix in triggering reduction in G0/G1, G2/M arrest, overriding the spindle checkpoint resulting in elevated apoptosis currently-reliant manner (Figure 3B). (
  • Inhibition of caspases allows the cells to go beyond the metaphase arrest, indicating that apoptosis is responsible for cell death by mitotic catastrophe. (
  • Inhibition of Chk2 thus can sensitize proliferating cells to chemotherapy-induced apoptosis. (
  • While p38 MAPK has classically been associated with the induction of apoptosis, we discuss that p38 MAPK can also mediate cell survival in specific situations, such as in response to DNA damage. (
  • Three are the most important consequences of the DDR activation: (i) the regulation of the cell cycle, throughout the activation of different cell cycle checkpoints, (ii) the activation of the mechanisms of DNA repair and (iii) the induction of the apoptosis when the errors are too extended to be fixed. (
  • Apoptosis of the cells was induced by CME. (
  • In case the cell is unable to repair the DNA it is then destined to apoptosis. (
  • If any DNA damage is detected that cannot be repaired, the cell may undergo apoptosis, or programmed cell death. (
  • Shah JV and Cleveland DW (2000) Waiting for anaphase: Mad2 and the spindle assembly checkpoint. (
  • Chapter 3 investigates how the spindle assembly checkpoint (SAC) is acquired at the MBT. (
  • The spindle assembly checkpoint detects errors in kinetochore attachment to the spindle including insufficient microtubule occupancy and absence of tension across bi-oriented kinetochore pairs. (
  • As outlined in Table 1 , we will focus our attention on drugs targeting key players of the S and G2/M checkpoints activated in response to DNA damage and on drugs targeting the mitotic spindle assembly checkpoint (SAC). (
  • The spindle assembly checkpoint (SAC) is based on the concerted action of numerous components that maintain a repressive signal inhibiting transition into anaphase until all chromosomes are attached. (
  • This event is triggered by the activation of M-Cdk in late prophase I. Then the spindle assembly checkpoint examines the attachment of microtubules at kinetochores, followed by initiation of metaphase I by APCCdc20. (
  • Here we show that human cells lacking Chk1 exhibit defects in both the ionizing radiation (IR)-induced S and G 2 checkpoints. (
  • The IR-induced S and G 2 checkpoints were partially restored in Chk1-deficient cells when Cdc25A accumulation was interfered with. (
  • Mouse embryos and conditional embryonic stem cell lines lacking Chk1 exhibit defective checkpoint responses to replication blocks and DNA-damaging agents establishing a checkpoint function for Chk1 in mice ( 8 , 9 ). (
  • Evidence that Chk1 contributes to G 2 checkpoint control in human cells comes from studies showing that agents such as UCN-01 and SB-218078, which are potent inhibitors of Chk1, abrogate G 2 checkpoint function in human cells ( 10-12 ). (
  • The contribution made by Chk1 to the IR-induced DNA damage checkpoint in humans remains controversial. (
  • In this study, we investigated the contribution made by human Chk1 to the cell division cycle both in the absence and presence of checkpoint activation. (
  • We report that cells deficient in human Chk1 exhibit radio-resistant DNA synthesis and do not delay in G 2 after IR treatment. (
  • Mechanistic data revealed that xanthatin downregulated Chk1, Chk2, and phosphorylation of CDC2, which contributed to the cell cycle arrest. (
  • I conclude that the lack of Chk1 activity prior to the MBT limits DNA damage checkpoint function during cleavage cycles. (
  • The cells were treated (+) with ionizing radiation (8.0 Gy) or TSA (300 nmol/L), or left untreated (−), in the absence ( top ) or presence ( bottom ) of the CHK1 inhibitor UCN-01 (100 nmol/L), and further incubated for 12 and 24 h before cellular DNA contents were determined by flow cytometry analysis gated for Hoechst 33258 fluorescence. (
  • Cell cycle regulatory factors and CHK1 signaling after exposure of MA-11 cells to ionizing radiation ( IR ) or the HDAC inhibitor TSA. (
  • The cells were treated (+) with ionizing radiation (8.0 Gy) or TSA (300 nmol/L), or left untreated (−), in the absence (−) or presence (+) of the CHK1 inhibitor UCN-01 (100 nmol/L). Expression levels of mRNAs for PLK, CCNB1 , and CDKN1A after 0 to 24 h were analyzed by Northern blot hybridization. (
  • It has been shown that CHK1 can phosphorylate Wee 1 in vitro , providing evidence that the hyperphosphorylated form of Wee 1, seen in cells delayed by CHK1 over-expression, is due to phosphorylation by CHK1. (
  • The CtIP/BRCA1 complex only exists in G 2 phase and is required for DNA damage-induced Chk1 phosphorylation and the G 2 /M transition checkpoint. (
  • In the colony survival assays, Rad17 −/− DT40 cells showed greater sensitivity to pierisin-1-induced cytotoxicity than wild-type and ATM −/− DT40 cells, possibly due to defects of checkpoint responses, such as the Chk1 activation. (
  • The contribution of Chk1 in the S- and G 2 -M-phase checkpoint is well understood to be mediated by phosphorylation of Cdc25A and Cdc25C, respectively ( 14 ). (
  • Thus, syncytia generated by the fusion of asynchronous HeLa cells contain elevated levels of active Chk2 but not Chk1. (
  • This laboratory previously demonstrated that UCN-01 , an inhibitor of Chk1/2 activity , also abrogates G 2 arrest and sensitizes p53-defective cells to DNA damage . (
  • Control mechanisms enforcing dependency in the cell cycle are here called checkpoints. (
  • Chapter 2 also shows the mechanisms governing DNA damage checkpoint acquisition at the MBT. (
  • Cell cycle checkpoints constitute regulatory mechanisms that do not allow a new phase of the cell cycle to proceed before the previous one is completed ( 6 ). (
  • Cells do not routinely express all DNA repair mechanisms, but instead upregulate these functions as required, concomitantly slowing the cell cycle to permit time for repair before S-phase (as replication past damaged sites may be mutagenic) or before M-phase (after which point double-strand breaks and lesions in daughter strand gaps may become far more problematic to repair). (
  • Understanding the genetic and biochemical mechanisms that govern the cell cycle could lead to new and better cancer therapies that kill cancer cells but are not toxic to normal cells. (
  • Taken together, these data not only implicate CtIP as a critical player in cell cycle checkpoint control but also provide molecular mechanisms by which BRCA1 controls multiple cell cycle transitions after DNA damage. (
  • We do find that activation of the DNA replication and spindle assembly checkpoints can fully arrest the network oscillator via overlapping but distinct mechanisms. (
  • In contrast, little is known regarding molecular mechanisms of checkpoint responses elicited in mammalian cells by other form of DNA damage, such as bulky adducts. (
  • Such a complex life-cycle presumably requires sophisticated global and local regulators, involving refined checkpoint and DNA repair mechanisms [ 3 ], yet these are currently only poorly understood. (
  • The available information suggests that surveillance mechanisms or 'checkpoints' which are known to regulate the eukaryotic cell cycle may be absent or altered in E. histolytica. (
  • Major currently used anticancer therapeutics either directly damage DNA or target and upset basic cell division mechanisms like DNA replication and chromosome segregation. (
  • These insults elicit activation of cell cycle checkpoints, safeguard mechanisms that cells implement to correctly complete cell cycle phases, repair damage or eventually commit suicide in case damage is unrepairable. (
  • Although cancer cells appear to be advantageously defective in some aspects of checkpoint physiology, recent acquisitions on the biochemical mechanisms of the various checkpoints are offering new therapeutic approaches against cancer. (
  • Indeed, chemical manipulation of these mechanisms is providing new therapeutic strategies and tools to increase the killing efficacy of major cancer therapeutics as well as to directly promote cancer cell death. (
  • The mechanisms of cell division and the genome itself are routinely endangered by endogenous and exogenous insults. (
  • Cancer cells are often defective in these checkpoint mechanisms [ 3 ]. (
  • Walworth NC (2000) Cell‐cycle checkpoint kinases: checking in on the cell cycle. (
  • Increased expression of wild-type p53 in response to DNA damage arrests cells late in the G1 stage of the cell cycle by stimulating the synthesis of inhibitors of cyclin-dependent kinases, such as p21/WAF1. (
  • Cell cycle events are regulated by the sequential activation and deactivation of cyclin dependent kinases (Cdks) and by proteolysis of cyclins. (
  • In budding yeast, Mec1 and Rad53 kinases ( homologous to mammalian ATM/ ATR and Chk2 kinases, respectively) are the main effectors of this checkpoint control. (
  • Nek family of kinases in cell cycle, checkpoint control and cancer. (
  • Abstract The eucaryotic cell cycle is regulated by the periodic synthesis and destruction of cyclins that associate with and activate cyclin-dependent kinases. (
  • Multiple signaling molecules, notably cyclins and the cyclin-dependent kinases (CDKs), play major roles in the cell cycle checkpoint’s control. (
  • The meiotic roles of the canonical checkpoint kinases Bub1, Mps1, the pseudokinase BubR1 (Mad3), and Aurora B and C (Ipl1) will be discussed. (
  • The cell cycle is driven by cyclin-dependent kinases (CDKs), which are activated by binding to cyclins that are specific for the different phases of the cell cycle and determine the targets of the kinases. (
  • 2000-=-). These differences in cell death regulation may explain why no p53 homologue has been reported in the sequenced genomes of these organisms. (
  • In plants, however, the regulation of DNA replication and repair and the cell cycle in response to DNA damage is only beginning to be understood. (
  • Up-regulation of miR-494 in cancer cells decreased growth, consistent with a functional role. (
  • Our findings demonstrate that miR-494 is down-regulated in CCA and that its up-regulation induces cancer cell growth retardation through multiple targets involved in the G1-S transition. (
  • Expansion of the Nek family throughout evolution has been accompanied by their broader involvement in checkpoint regulation and cilia biology. (
  • A second type of cell cycle regulation, checkpoint control, is more supervisory. (
  • Posted in Biology PPT, Cell & Molecular Biology PPT, Molecular Biology and tagged Cell Cycle Checkpoint PPT, Cell Cycle Regulation PPT, Control of Cell Cycle PPT, G1 Checkpoint, G2 Checkpoint, M Checkpoint, Molecular Biology PPT. (
  • Free Molecular Biology PPT: The Molecular Mechanism of Cell Cycle Regulation and Cancer by Cell Cycle Checkpoints such as G1 Checkpoint, M Checkpoint and G2 to controlofcell cycle transitions. (
  • A recent in-depth view of cell cycle regulation and cancer has provided novel samples of research at the "Frontiers of Science. (
  • However, the number of foremost revealing information about both the topics has been derived from the intersection of these two fields.1-5 This review intends to introduce the basics of the cell cycle and its regulation at different checkpoints in relation to cancer. (
  • Finally, transcription factors within the nucleus must initiate the transcription of genes involved in cell proliferation. (
  • Hoyt MA, Totis L and Roberts BT (1991) S. cerevisiae genes required for cell cycle arrest in response to loss of microtubule function. (
  • In addition, checkpoints respond to damage by arresting the cell cycle to provide time for repair and by inducing transcription of genes that facilitate repair. (
  • 1 Functional promoter SNPs in cell cycle checkpoint genes. (
  • D ow nloaded from 2 A substantial number of genes mutated in human cancers encode components of the cell cycle processes. (
  • Since the G1/S transition in the cell cycle is a finely regulated biological process we hypothesized that sequence variations in the promoter region of the related genes might indeed lead to abnormal expression, thus predisposing the individuals carrying these genetic variants to cancer. (
  • In this report we screened the promoter regions of 16 cell cycle checkpoint genes for DNA variants and assessed the functional impact of these promoter SNPs (pSNPs) by combining in silico analysis and in vitro functional assays. (
  • Saccharomyces cerevisiae checkpoint genes MEC1, RAD17 and RAD24 are required for normal meiotic recombination partner choice. (
  • It has also been shown that although this organism contains sequence homologs of genes which are known to control the cell cycle of most eukaryotes, these genes may be structurally altered and their equivalent function yet to be demonstrated in amoeba. (
  • Our observations that bimA9 and bimA10 strains had morphologically abnormal nuclei, chromosome segregation defects, synthetic phenotypes with mutations in the DNA damage checkpoint genes uvsB MEC1/rad3 or uvsD + , and enhanced sensitivity to hydroxyurea strongly suggest that these strains accumulate errors in DNA metabolism. (
  • The function of eight of the genes identified has not been previously defined in The genes identified included those with known or predicted functions in cell cycle, chromosome segregation, morphogenesis, metabolism, steroid processing, transcription, and translation. (
  • To identify genes required for damage survival, we used a cell-based RNAi screen against the Drosophila genome and the alkylating agent methyl methanesulphonate (MMS). (
  • see the Perspective by Weinert) describe experiments in which uncompleted replication of ribosomal DNA (rDNA) genes does not prevent cells from proceeding into anaphase. (
  • In p53 wild-type cells , S phase arrest was maintained in the presence of UCN-01 , by p53-mediated transcriptional activation of target genes such as p21 . (
  • The tumor cell response to DNA damage involves a temporary cell cycle delay at the G 1 -S or G 2 -M boundaries, to activate a cascade of responses to the damage, ultimately leading to cell survival if the DNA is properly repaired, or, if not, to apoptotic or mitotic cell death ( 7 ). (
  • CHK 1 and CHK 2 both function as essential components in the G2 DNA damage checkpoint by phosphorylating CDC25C in response to DNA damage. (
  • In response to DNA damage, the 9-1-1 complex will be loaded onto the DNA damage site by clamp loader Rad24-RFC to activate the cell cycle checkpoint. (
  • In response to DNA damage, cell cycle checkpoints can be activated in G1 phase, in S phase and at the G2/M transition [ 9 , 10 ]. (
  • The G1 checkpoint, also known as the restriction point in mammalian cells and the start point in yeast, is the point at which the cell becomes committed to entering the cell cycle. (
  • Hartwell LH, Culotti J, Pringle JR and Reid BJ (1974) Genetic control of the cell division cycle in yeast. (
  • Nurse P (1975) Genetic control of cell size at cell division in yeast. (
  • we have looked at how the budding yeast spindle checkpoint is regulated as cells leave metaphase. (
  • Using a yeast based screen, we have identified a compound ( named here ENA) which inhibits DNA replication and activates Mec1/ Rad53 checkpoint. (
  • CDKs are also the central components of the oscillator in many contemporary models of yeast and metazoan cell-cycle control. (
  • A cell cycle checkpoint monitors cell morphogenesis in budding yeast. (
  • In the budding yeast Saccharomyces cerevisiae, DNA replication and spindle assembly are monitored by checkpoint controls that prevent nuclear division in cells that have failed to complete these processes. (
  • These results suggest the existence of a novel checkpoint that monitors cell morphogenesis in budding yeast. (
  • The fission yeast cell cycle. (
  • Schematic diagram of a proposed molecular mechanism for three checkpoint controls in the fission yeast cell cycle. (
  • In human, the comparable DNA damage checkpoint components, Rad17 and the Rad1-Rad9-Hus1 (9-1-1) complex, play similar roles in DNA damage surveillance and checkpoint activation as their counter partners (Rad24, Rad17-Mec3-Ddc1) in budding yeast. (
  • Yeast Rad17/Mec3/Ddc1: a sliding clamp for the DNA damage checkpoint. (
  • Cell cycle process of budding yeast ( Saccharomyces cerevisiae ) consists of four phases: G1, S, G2 and M. Initiated by stimulation of the G1 phase, cell cycle returns to the G1 stationary phase through a sequence of the S, G2 and M phases. (
  • In particular, such models violate the M phase checkpoint condition so that it allows a division of a budding yeast cell into two before the completion of its full DNA replication and synthesis. (
  • To our knowledge this is the first work that rigorously examined the timing robustness of the cell cycle process of budding yeast with respect to checkpoint conditions using Boolean models. (
  • Unexpectedly, yeast--a widely used organism for cell cycle studies--does not have a mechanism to prevent cell division if DNA replication is still incomplete. (
  • Genetic screens in budding yeast identified many checkpoint components. (
  • UCN-01 did not demonstrate this selectivity for checkpoint inhibition. (
  • We compared profiles of in vitro MA-11 cell cycle response to ionizing radiation and HDAC inhibition. (
  • Inhibition of Chk2 again facilitated the induction of mitotic catastrophe in HCT116 wild-type cells. (
  • Optimized inhibitors display many of the hallmarks of Aurora inhibition including endoreduplication, polyploidy, and loss of cell viability in cancer cells. (
  • Efforts to determine whether absence or inhibition of CENP-E affects kinetochore-dependent mitotic checkpoint signaling have come to sharply divergent conclusions. (
  • A human homologue of the Schizosaccharomyces pombe rad1+ checkpoint gene encodes an exonuclease. (
  • Here, we demonstrate that short-term silencing of the Rad51 gene by specific small interfering RNA (siRNA) that inhibits cell proliferation and reduces the viability of most cells. (
  • Cells with suppressed expression of Rad51 gene have altered cell cycles and accumulate in the S and G 2 phases. (
  • MCF-7 cells, are insensitive to the suppression of Rad51 gene expression. (
  • MA-11 cells did not show radiation-induced expression of the G 1 cell cycle inhibitor p21, indicative of a defective G 1 checkpoint and consistent with a point mutation detected in the tumor suppressor TP53 gene. (
  • The results showed that M2 cells lost MMR activity as well as the previously introduced normal hMLH1 gene. (
  • Top, exons 2 to 11 of the TP53 gene were individually amplified by PCR from DNA extracted from the cell lines, and further analyzed by the constant denaturant gel electrophoresis method. (
  • The p53 tumor-suppressor gene integrates numerous signals that control cell life and death. (
  • Purpose There is evidence to suggest that the breast cancer predisposing gene, BRCA1, is involved in cell cycle control and the response to damage but mouse brca1+/− heterozygotes have no distinctive phenotype. (
  • HRad17, a human homologue of the Schizosaccharomyces pombe checkpoint gene rad17, is overexpressed in colon carcinoma. (
  • The Aspergillus nidulans sepI + gene has been implicated in the coordination of septation with nuclear division and cell growth. (
  • In addition, studies of the mRNA levels of p53 and its effector gene p21 revealed that although both cell lines expressed p53 mRNA, a marked difference in the mRNA levels of p21 was seen. (
  • 19 ]. Even with such a simple representation, they found that there exists a prominent dynamic gene expression trajectory satisfying the checkpoint conditions, and then it leads back to the G1 stationary state. (
  • Cancer is the result of uncontrolled cell division sparked by a gene mutation. (
  • As in the mitotic cycle, these transitions are regulated by combinations of different gene regulatory factors, the cyclin-Cdk complex and the anaphase-promoting complex (APC). (
  • The scheduled activity of the cdks, which allows orderly transition between cell cycle phases, is controlled by their association with cyclins and cdk inhibitors, by their state of phosphorylation, and by ubiquitin-mediated proteolysis. (
  • Among molecular cell cycle-targeted drugs currently in the pipeline for testing in early-phase clinical trials, HDAC inhibitors may have therapeutic potential as radiosensitizers. (
  • Furthermore, gastric cancer cells resistant to HDAC inhibitors were vulnerable to MPT0L184. (
  • Although the great amount of pre-clinical and clinical data are from the solid tumor experience, only few studies have been done on leukemias using specific cell cycle checkpoint inhibitors. (
  • This review, for the first time, outlines the most important pre-clinical and clinical data available on the efficacy of cell cycle checkpoint inhibitors in single agent and in combination with different agents normally used for the treatment of acute and chronic leukemias. (
  • Other novel , structurally related checkpoint inhibitors ICP-1 and Gö6976 also abrogated arrest , but did not appear to inhibit C-TAK1 . (
  • These results will facilitate the development of checkpoint inhibitors as anticancer drugs . (
  • Current Opinion in Cell Biology 12: 697-704. (
  • Trends in Cell Biology 10: 154-158. (
  • Trends in Cell Biology 10: 296-303. (
  • have you already searched in 'Molecular Biology of the Cell' bij Alberts et al. (
  • Cell cycle analysis is a method in cell biology that employs flow cytometry to distinguish cells in different phases of the cell cycle. (
  • T-Cell Costimulation Biology, Therapeutic Potential, and Challenges. (
  • At Cell Systems, we talk a lot about systems biology, what it is, and how the journal encompasses and yet is bigger than this label. (
  • Abstract] The flow cytometric quantitation of DNA content by DNA-binding fluorochrome, propidium iodide (PI) is the most widely used method for cell cycle analysis. (
  • Canman CE (2001) Replication checkpoint: preventing mitotic catastrophe. (
  • DNA replication checkpoint is activated in response to replication stresses. (
  • These checkpoint controls are essential for maintaining genomic integrity and balanced growth and division. (
  • The genomic integrity of a cell is constantly being pressured by both intrinsic and extrinsic forces. (
  • and the metaphase-to-anaphase transition, also known as the spindle checkpoint. (
  • Repressing the target of the spindle checkpoint, the multisubunit ubiquitin ligase, the anaphase promoting complex (APC) stabilized MPS1 and allowed the checkpoint to be reactivated. (
  • Taken together, these results suggest that the target of the spindle checkpoint, the APC, feeds back on at least one checkpoint component to regulate checkpoint activity at the metaphase to anaphase transition. (
  • In summary, the opposing activities of the checkpoint and the APC let cells switch rapidly between metaphase, when they can sensitively monitor chromosome alignment, and anaphase, when they are irreversibly committed to entering the next cell cycle. (
  • Some cells have a quality control checkpoint that can detect a single misattached chromosome and delay the onset of anaphase, thus allowing time for error correction. (
  • Equally direct experiments identify tension as the checkpoint signal: tension from a microneedle on a misattached chromosome leads to anaphase (Li, X., and R. B. Nicklas. (
  • In between the beginning and end stages, the dividing cell passes through the stages of metaphase, anaphase and telophase. (
  • The following stage, anaphase, is the shortest portion of the cell division process. (
  • This checkpoint guarantees that anaphase onset is initiated only when all chromosomes are properly attached to microtubules and aligned at the metaphase plate. (
  • The M, or spindle, checkpoint ensures that all the sister chromatids are correctly attached to the spindle microtubules at the metaphase plate before the cell enters anaphase. (
  • Maintenance of ploidy is ensured through action of the mitotic checkpoint, which prevents the transition to anaphase until all chromosomes have made productive, bipolar attachments through their kinetochores to the microtubules of the mitotic spindle. (
  • AKAP95-depleted cells display faster prometaphase to anaphase transition, escape from nocodazole-induced mitotic arrest and show a partial delocalization from kinetochores of the SAC component MAD1. (
  • IR-induced cell-cycle checkpoint function was also defective, and induction of p21 was attenuated in thymus from Atm-deficient mice. (
  • However, Gö6976 potently abrogated S and G 2 arrest and enhanced the cytotoxicity of the topoisomerase I inhibitor SN38 only in p53-defective cells. (
  • The human colon tumor cell line HCT116 is deficient in wild-type hMLH1 , is defective in mismatch repair (MMR), exhibits microsatellite instability, and is tolerant to N -methyl- N′ -nitro- N -nitrosoguanidine (MNNG). (
  • G2 arrest also was observed in wild-type plants in response to aphidicolin but was defective in atr mutants, resulting in compaction of nuclei and subsequent cell death. (
  • The display screen identified a fresh checkpoint-defective allele of truncated on the C terminus. (
  • We discovered that checkpoint-defective alleles suppress the MMS awareness as well as the checkpoint recovery defect of cells. (
  • Because a defective G1/S checkpoint in BRCA1 heterozygotes could lead to a greater proportion of S-phase cells with unrepaired DNA damage (strand breaks) and a resultant increase in chromosomal instability, the frequency of micronuclei induced by UVA was examined. (
  • Conclusion Our data suggest a defective G1/S checkpoint in cells from BRCA1 heterozygotes in response to UVA although this is not reflected in genomic instability as measured by micronuclei induction after oxidative stress or MMC treatment. (
  • Here, we examined the mechanism of S phase arrest induced by the topoisomerase I inhibitor SN38 in p53-defective breast cancer cells and p53 wild-type breast cells . (
  • Furthermore, xanthatin blocked phosphorylation of NF-κB (p65) and IκBa, which might also contribute to its pro-apoptotic effects on A549 cells. (
  • Furthermore, apoptotic 50-kb DNA fragmentation was observed in the HeLa cells, which was well correlated with occurrence of phosphorylation of Chk2. (
  • Chk2 bearing the activating phosphorylation on threonine-68 accumulates in BRCA1 nuclear bodies when the cells arrest at the G2/M boundary. (
  • Using detergent-extracted S2 cells as a system in which kinetochore phosphorylation can be easily manipulated, we observed that BubR1 and Bub3 accumulation at kinetochores is dependent on the presence of phosphorylated 3F3/2 epitopes. (
  • Elimination of checkpoints may result in cell death, infidelity in the distribution of chromosomes or other organelles, or increased susceptibility to environmental perturbations such as DNA damaging agents. (
  • Left) Prior to metaphase, chromosomes that are incorrectly aligned on the mitotic spindle generate a signal that activates the spindle checkpoint. (
  • When chromosomes segregate into daughter nuclei it is too late for chromosome alignment to be corrected, and a cell cycle delay caused by spindle checkpoint activation would be disadvantageous. (
  • The process of chromosome separation generates chromosomes attached to a single spindle pole, one of the signals that would normally activate the spindle checkpoint. (
  • Thirdly, at metaphase, the cell ensures that all chromosomes are correctly aligned on the central plate before they are separated to opposite poles of the spindle. (
  • Telomeres protect the ends of eukaryotic chromosomes, and telomere shortening causes irreversible cell-cycle arrest through activation of the DNA-damage checkpoint. (
  • The longest stage is metaphase, during which the cell's chromosomes are aligned along an imaginary line (the metaphase plate), which divides the cell into two halves. (
  • Once all chromosomes are properly attached, the SAC-dependent arrest is relieved and chromatids separate evenly into daughter cells. (
  • All sexually reproducing organisms rely on a specialized form of cell division known as meiosis, the defining feature of which is the generation of gametes with half the number of chromosomes of the parental cell. (
  • One of the important differences between plasmids and chromosomes is that the latter replicate during a defined period of the cell cycle, ensuring a single round of replication per cell. (
  • Vibrio cholerae carries two circular chromosomes, Chr1 and Chr2, which are replicated in a well-orchestrated manner with the cell cycle and coordinated in such a way that replication termination occurs at the same time. (
  • Our study reveals a new checkpoint control mechanism in bacteria, and highlights possible functional interactions mediated by contacts between two chromosomes, an unprecedented observation in bacteria. (
  • Loss or gain of chromosomes during mitotic divisions leads to the production of cells with a DNA content greater or less than 2N, a condition known as aneuploidy, which is a hallmark of cancer cells. (
  • The mitotic checkpoint is a molecular mechanism that prevents premature segregation until all chromosomes are bioriented and aligned at the metaphase plate. (
  • The special chromosome separation in meiosis, homologous chromosomes separation in meiosis I and chromatids separation in meiosis II, requires special tension between homologous chromatids and non-homologous chromatids for distinguishing microtubule attachment and it relies on the programmed DNA double strand break (DSB) and repair in prophase I. Therefore meiotic recombination checkpoint can be a kind of DNA damage response at specific time spot. (
  • Therefore the unsynapsed chromosomes in Spo11 cells can be a target of checkpoint. (
  • this fact may pose special problems for the fidelity of embryonic cell division. (
  • MMR-deficient HCT116 cells or embryonic fibroblasts from MLH1 knockout mice also demonstrated classic DNA damage tolerance responses after 6-TG exposure. (
  • The life cycle of a dividing non embryonic eukaryotic cell starts with it entering the cell cycle and enter with equal partitioning of the genetic material and cleavage by cytokinesis. (
  • Polyploidy is often witnessed in cells prior to differentiation, in embryonic cells or in diseases such as cancer. (
  • However, little is known about checkpoint responses elicited in mammalian cells by the formation of such bulky DNA adducts. (
  • It seems most likely that lots of mammalian cells resemble Schwann cells in this respect. (
  • We've been learning how this coordination is normally attained in mammalian cells, using principal rat Schwann cells being a model program Polidocanol [2]. (
  • It is also unfamiliar whether mammalian cells have cell-size checkpoints, although it is definitely widely believed that they are doing [3,7-9]. (
  • For most populations of proliferating eukaryotic cells in tradition, including candida cells and mammalian cells, the mean cell size remains constant over time, even though individual Polidocanol cells vary in size at division [10]. (
  • Checkpoint loss results in genomic instability and has been implicated in the evolution of normal cells into cancer cells. (
  • Components of the cell cycle machinery are frequently altered in human cancer. (
  • Here, we review key aspects of cell cycle and checkpoint control, as well as exploitable abnormalities commonly found in cancer, in order to focus on promising targets of new agents presently in clinical trial or under development. (
  • Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancer cells, yet little is known about its anticancer mechanism. (
  • In this study, we demonstrated that xanthatin had obvious dose-/time-dependent cytotoxicity against the human non-small-cell lung cancer (NSCLC) cell line A549. (
  • Genomic instability results when the strict order of cell cycle events breaks down, and inactive checkpoints are often associated with aneuploidy, a common feature of cancer cells. (
  • Many cancer chemotherapy drugs currently in use ( e.g. , cisplatin, mitomycin C, camptothecin, and etoposide) are DNAdamaging agents and arrest cells in the G 1 , S, or G 2 phases of the cell cycle. (
  • In this study, we report a selective entinostat derivative, MPT0L184, with potent cancer-killing activity in both cell-based and mouse xenograft models. (
  • University of Iowa Roy J. and Lucille A. Carver College of Medicine researchers in the UI Holden Comprehensive Cancer Center have been awarded a five-year, $1.5 million grant from the National Cancer Institute to investigate a new hypothesis about how the mammalian cell cycle is regulated. (
  • In non-cancer cells, changing the cellular redox state with an antioxidant prevents progress into the S-phase of the cycle. (
  • The same treatment does not affect the cancer cell cycle. (
  • In contrast, cancer cells with defects in redox-sensitive checkpoints will continue to proliferate,' explained Goswami, who also is a co-director of the Free Radical Research Core in the Holden Comprehensive Cancer Center at the UI. (
  • If redox control of the cell cycle is different in normal cells than in cancer cells, that difference potentially could be exploited to develop new redox-based cancer therapies. (
  • Interestingly, ENA acts as an effective anti - proliferative agent against a subset of cancer cell lines and as an anti - tumor agent against human xenografts in mice. (
  • Primary fibroblasts from BRCA1 mutation-carrying members of breast cancer families display a G1/S cell cycle checkpoint defect following UVA irradiation but show normal levels of micronuclei following oxidative stress or mitomycin C treatment. (
  • one-day techniques of attached download Cell Cycle Checkpoints and Cancer and scholarship, the PH of century to enable share, and the reporting of things quite was the cell of participants and the romanticism of mollusc. (
  • The putting download Cell Cycle Checkpoints and Cancer for this hypothesis involves the Sausage member fall. (
  • Postal Service nurturing brief download Cell Cycle Checkpoints and Cancer politics by order strategies in East Cleveland, Ohio. (
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  • We investigated the antitumor effect of Cordyceps militaris extract (CME) on A549 cisplatin-resistant (CR) lung cancer cells. (
  • We have treated two human breast cancer cell lines that differ in p53 status with epirubicin in order to study if there are differences in cell cycle kinetic response. (
  • Hartwell, L 1995, ' 1994 Forbeck Cancer Forum on Cell Cycle Checkpoints ', Clinical Cancer Research , vol. 1, no. 9. (
  • therefore, cell cycle regulators are considered attractive targets in cancer therapy. (
  • In this review we summarize developing concepts on how targeting cell cycle checkpoints may provide substantial improvement to cancer therapy. (
  • Nevertheless, the actual information on checkpoint biochemistry and its deregulation in cancer, along with the development of relative pharmacologic tools, is now offering new opportunities for cancer treatment. (
  • DNA damage-induced cell cycle checkpoints as a target for cancer therapy. (
  • However, cancer cells often bypass these checkpoints. (
  • The DNA binding domain (DBD) within the hLigI catalytic fragment interacts with both PCNA and the heterotrimeric cell-cycle checkpoint clamp, hRad9-hRad1-hHus1 (9-1-1). (
  • A cell cycle works with the interaction of cyclins and cdks. (
  • The C-terminal of Ddc1/Rad9 is critical for checkpoint activation. (
  • Intramolecular binding of the rad9 C-terminus in the checkpoint clamp Rad9-Hus1-Rad1 is closely linked with its DNA binding. (
  • Indeed Rad53 dephosphorylation is sufficient for fork restart during checkpoint recovery (Szyjka 2008). (
  • Because Rad53 is definitely constitutively phosphorylated in the absence of Dia2 (Pan 2006) it seems unlikely that Dia2 is required for checkpoint activation. (
  • Consistent with the data showing hyperactivation of Rad53 in cells DNA replication is definitely sluggish in cells in the presence of MMS (Blake 2006). (
  • We found that the aseptate phenotype of bimA9 and bimA10 strains was substantially relieved by mutations in uvsB MEC1/rad3 or uvsD + , suggesting that the presence of a functional DNA damage checkpoint inhibits septation in these bimA APC3 strains. (
  • In this in vivo genetic analysis in Drosophila melanogaster, we establish that disruption of complex I of the mitochondrial electron transport chain specifically retards the cell cycle during the G1-S transition. (
  • After a constant, organism-specific number of cleavages, many metazoan embryos undergo the mid-blastula transition (MBT), which initiates extensive cell cycle remodeling. (
  • Introduction of a nocodazole-induced G2-M block, which corrected the MLH1-mediated G2-M arrest deficiency in HCT116 cells, clearly demonstrated that HCT116 and HCT116 3-6 cells did not differ in G1 arrest or G1-S cell cycle transition after IR. (
  • Thus, our data indicate that MLH1 does not play a major role in G1 cell cycle transition or arrest. (
  • Further analyses demonstrated that miR-494 down-regulates multiple molecules involved in this transition checkpoint. (
  • The transition of cells from one cell cycle stage to another was studied by a bromodeoxyuridine (BrdUrd)-flow cytometry (FCM) method. (
  • the feedback circuit provides an example of a simple mechanism the cell can use to help solve this regulatory problem. (
  • however , the mechanism of the S phase checkpoint has remained unclear . (
  • How cells use checkpoints at the end of G1 phase, end of G2 phase, and partway through M phase (the spindle checkpoint) to regulate the cell cycle. (
  • Cell growth occurs in all phases of the cell cycle except M phase [1,3]. (
  • The Gap phases of the cell cycle are essential to perceive internal and external signals and control cell division and differentiation. (
  • The g 1 phase, or Gap 1 phase, is the first of four phases of the cell cycle that takes place in eukaryotic cell division. (
  • Kinetochore chemistry is sensitive to tension and may link mitotic forces to a cell cycle checkpoint. (
  • To analyse the behaviour in the absence of tension, we treated S2 cells with low doses of taxol to disrupt microtubule dynamics and tension, but not kinetochore-microtubule occupancy. (
  • When the last kinetochore attaches to microtubules the checkpoint becomes satisfied, allowing APC activation and progress towards mitotic exit. (
  • it is appropriately positioned to serve as a sensor linking microtubule capture to underlying kinetochore-bound checkpoint components. (
  • My download Cell Cycle Checkpoints: Methods and Protocols on the XLR Migration! (
  • These observations demonstrate selectivity for enhancing toxicity in cells with mutated p53 (many tumor cells), whereas cells with wild-type p53 (normal cells) are spared. (
  • sntA1, sntB1 , and sntC1 mutants undergo septum formation at a smaller size and with fewer nuclei than do wild-type cells. (
  • In response to stress stimuli that cause DNA damage, cells undergo cell cycle checkpoints to allow time for DNA repair. (
  • Multinucleated muscle cells that do not undergo cytokinesis are also often considered to be in the G0 stage. (
  • Cells undergo a complex cycle of growth and division that is referred to as the cell cycle. (
  • Experiments with various mitotic mutants have demonstrated that this pattern of growth, nuclear division, and septation are dependent on controls that ensure that germlings acquire a minimum threshold cell size and undergo at least one nuclear division before cytokinesis. (
  • Early mutants ( sepB , E , I , and J ) undergo only approximately three nuclear divisions in the presence of an extending germ tube before arresting growth as aseptate cells. (
  • A cell must undergo the process of duplicating all its components and separating them, more or less evenly, to two daughter cells such that each daughter has the information and dynamics necessary to repeat the process. (
  • The cell cycle checkpoints play an important role in the control system by sensing defects that occur during essential processes such as DNA replication or chromosome segregation, and inducing a cell cycle arrest in response until the defects are repaired. (
  • Pardee AB (1974) A restriction point for control of normal animal cell proliferation. (
  • Another hallmark of the transformed state is incompetent checkpoint control, resulting in aberrant responses to cellular damage. (
  • Cells in which checkpoint control is disrupted are more sensitive to additional genotoxic or microtubular damage. (
  • Middle,TP53 mRNA expression in the cell lines was analyzed by Northern blot hybridization using 18S rRNA as RNA loading control. (
  • Thus, the BRCT domain is likely to perform critical, yet uncharacterized, functions in the cell cycle control of organisms from bacteria to humans. (
  • It is over 100 years since the life-cycle of the malaria parasite Plasmodium was discovered, yet its intricacies remain incompletely understood - a knowledge gap that may prove crucial for our efforts to control the disease. (
  • The G1/S cell cycle checkpoints control whether eukaryotic cells enter the S phase (synthesis phase) of DNA synthesis through the G1 phase. (
  • Before division, cells must ensure that they finish DNA replication, DNA repair and chromosome segregation. (
  • Several rounds of genome reduplication before chromosome segregation upsets this cycle and leads to polyploidy. (
  • Here, we summarize the main differences between mitotic and meiotic cell divisions, and explain why meiotic divisions pose special challenges for correct chromosome segregation. (
  • No. R1536 shows detection of a predominant band at ~60 kDa corresponding to phosphorylated CHK2 (arrowhead) in MCF-7 whole cell lysates after treatment with doxorubicin. (
  • In another, completely different model of mitotic catastrophe, namely 14.3.3 -deficient HCT116 colon carcinoma cells treated with doxorubicin, Chk2 activation was also found to be deficient as compared to 14.3.3 -sufficient controls. (
  • The Rad24-RFC complex is involved in both the mitotic and meiotic checkpoints [ PMID: 10511543 ]. (
  • The stages G1, S, and G2 make up interphase, which accounts for the span between cell divisions. (
  • The time in between the five stages is called the interphase and represents the longest part of the cell cycle. (
  • In eukaryotic cells, the somatic cell cycle has two stages: interphase and the mitotic phase. (
  • During interphase, the cell grows, performs its basic metabolic functions, copies its DNA, and prepares for mitotic cell division. (
  • If the cell is deemed inadequate, it does not continue to the S phase of interphase. (
  • Further, accumulation of unrepaired meiotic recombination intermediates can also lead to the apoptotic demise of affected pachytene cells. (
  • The meiotic recombination checkpoint monitors meiotic recombination during meiosis, and blocks the entry into metaphase I if recombination is not efficiently processed. (
  • On the other hand, the meiotic recombination checkpoint also makes sure that meiotic recombination does happen in every pair of homologs. (
  • The decision to commit to a new round of cell division occurs when the cell activates cyclin-CDK-dependent transcription which promotes entry into S phase. (
  • On the basis of our data combined with previous analyses of the system, we conclude that mitochondrial dysfunction activates at least two retrograde signals to specifically enforce a G1-S cell cycle checkpoint. (
  • When DNA damage is detected, the Rad24-RFC complex loads Rad17-Mec3-Ddc1 complex onto chromatin and activates DNA damage checkpoint, which then leads to cell cycle arrest and DNA repair [ PMID: 12604797 ]. (
  • Here, we find that Arabidopsis ( Arabidopsis thaliana ) atr−/− mutants were viable, fertile, and phenotypically wild-type in the absence of exogenous DNA damaging agents but exhibit altered expression of AtRNR1 (ribonucleotide reductase large subunit) and alteration of some damage-induced cell-cycle checkpoints. (
  • If errors in chromosome alignment are detected, spindle checkpoint activity delays the cell cycle, which allows time for the defects to be corrected. (
  • We report that MLH1-deficient human colon carcinoma (HCT116) cells showed decreased survival and a concomitant deficiency in G2-M cell cycle checkpoint arrest after ionizing radiation (IR) compared with genetically matched, MMR-corrected human colon carcinoma (HCT116 3-6) cells. (
  • Here we discuss the role of p38 MAPK in the mediation of cell cycle checkpoints and cell survival, processes that have received less attention. (
  • The cellular stress response has a vital role in regulating homeostasis by modulating cell survival and death. (
  • Following pretreatment with the HDAC inhibitor, the efficiency of clonogenic regrowth after irradiation was reduced, which is in accordance with the concept of increased probability of mitotic cell death when the chromatin structure is disrupted. (
  • MA-11 cell cycle profiles on exposure to ionizing radiation ( IR ) or the HDAC inhibitor TSA. (
  • Thus, ENA is a potent cell cycle inhibitor with conceivable therapeutic potential. (
  • Thymidine is a DNA synthesis inhibitor that can arrest cell at G1/S boundary, prior to DNA replication. (
  • We describe how p38 MAPK regulates both the G2/M as well as a G1/S cell cycle checkpoint in response to cellular stress such as DNA damage. (
  • Zetterberg A and Larsson O (1985) Kinetic analysis of regulatory events in G1 leading to proliferation or quiescence of Swiss 3T3 cells. (
  • Cell proliferation occurs rapidly because cleavage cycles lack the gap phases and cell cycle checkpoints found in canonical cell cycles. (
  • This process, also known as proliferation, is usually tightly controlled, but in cancers the process goes awry and malignant cells proliferate in an uncontrolled manner. (
  • The proliferation of A549/CR cells was suppressed by CME. (
  • Keeping it All in Check: The Life of a Cell in the Cell Cycle The colored arrows depict complex signaling pathwaysthat operate in Gl to transmit information regarding cell proliferation. (
  • Here, we collate what is known about the various cell cycle events and their regulators throughout the Plasmodium life-cycle, highlighting the differences between Plasmodium , model organisms and other apicomplexan parasites and identifying areas where further study is required. (