AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Cell CycleCell Cycle ProteinsDNA DamageGenes, cdcCheckpoint Kinase 2G2 PhaseCell Cycle CheckpointsMitosisProtein-Serine-Threonine KinasesAtaxia Telangiectasia Mutated ProteinsS PhaseProtein KinasesDNA RepairHydroxyureaG2 Phase Cell Cycle CheckpointsSpindle ApparatusM Phase Cell Cycle CheckpointsG1 PhaseDNA-Binding ProteinsNuclear ProteinsGamma RaysTumor Suppressor Protein p53DNA ReplicationMad2 ProteinsSaccharomyces cerevisiae ProteinsSchizosaccharomycesTumor Suppressor ProteinsSchizosaccharomyces pombe ProteinsFungal ProteinsMutationSaccharomyces cerevisiaeAtaxia TelangiectasiaRadiation, Ionizingcdc25 PhosphatasesUltraviolet RaysChromosomal InstabilityPhosphorylationCyclinsCyclin-Dependent Kinase Inhibitor p21CDC2 Protein KinaseGenes, FungalCyclin BRadiation ToleranceApoptosisIntracellular Signaling Peptides and ProteinsCell DivisionGenomic InstabilityG1 Phase Cell Cycle CheckpointsMolecular Sequence DataDNA, FungalCyclin B1S Phase Cell Cycle CheckpointsCell Line, TumorCell LineSignal TransductionDNA Breaks, Double-StrandedNocodazoleHeLa CellsFibroblastsRetinoblastoma ProteinGene DeletionBase SequenceAneuploidyBRCA1 ProteinModels, BiologicalFlow CytometryRepressor ProteinsHistonesCDC28 Protein Kinase, S cerevisiaeCyclin-Dependent Kinase 2Chromosomes, FungalGenes, p53DNACell NucleusCell ProliferationKinetochoresPhenotypeTumor Cells, CulturedCell SurvivalMethyl MethanesulfonateDNA Repair EnzymesNeoplasm ProteinsCyclin ECells, CulturedMimosineRNA, Small InterferingCDC2-CDC28 KinasesGene Expression Regulation, NeoplasticCyclin-Dependent KinasesCalcium-Binding ProteinsProtein BindingCaffeineAmino Acid SequenceDose-Response Relationship, RadiationCyclin AAphidicolinNucleic Acid Synthesis InhibitorsAllelesTime FactorsPolyploidy
ApoptosisPathwaysMutationsProteinsKinaseCellularTumorsAberrantProgressionReplicationPathwayGeneticProliferationRegulationRegulatesGenome integrityBRCA1ApoptoticEpithelialTumor cellsTranscriptionRetinoblastoma tumor suppKinasesProcessesTarget genesArrestEmbryosPhenotypesGenomic instabilityHistoneMolecularMethylationInstabilityInduceMammalian cellsRestrictionProto-oncogenesFunctionalTranscriptionalOrganismsViabilityInhibitPhosphorylateExpressionResponse to DNA damageSquamous cell carcChromosomePhosphorylationMechanismsIntegrityMitosisCRISPRRadiationRepairAbnormalAbstractTP53Double strandAbnormalities
Apoptosis21
  • The genetic instability caused by BRCA1 deficiency, however, also triggers cellular responses to DNA damage that blocks cell proliferation and induces apoptosis. (nih.gov)
  • The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
  • TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
  • They have unusually rapid cell cycles, lack a DNA damage check-point, have reduced DNA repair capacity, and often cannot trigger apoptosis. (nih.gov)
  • Reactivation of these growth control genes may contribute to restoration of normal cell cycle or apoptosis checkpoints, but these agents cause DNA damage and induce a DNA double strand break response. (mayo.edu)
  • The model has four outcomes that convey alternative cell fates: proliferation, (transient) cell cycle arrest, apoptosis and senescence. (biomedcentral.com)
  • Among other components, the tumour suppressor p53 protein triggers cellular programs that lead to different fates: transient arrest followed by cell cycle re-entry upon damage repair, permanent cell cycle arrest (senescence) or, if the damage is irreparable, initiation of cell death program (apoptosis). (biomedcentral.com)
  • Based on functional enrichment analyses, up-regulated polyploidy genes appeared to implicate several functions, which primarily include cell/nuclear division, ATP binding, metabolic process, and mitochondrial activity, whereas that of down-regulated genes primarily included apoptosis and immune processes. (plos.org)
  • If a cell has an error in its DNA that cannot be repaired, it may undergo self-destruction ( apoptosis ). (medlineplus.gov)
  • Apoptosis is a common process throughout life that helps the body get rid of cells that no longer work or that it doesn't need. (medlineplus.gov)
  • Apoptosis protects the body by removing genetically damaged cells that could lead to cancer, and it plays an important role in the development of the embryo and the maintenance of adult tissues. (medlineplus.gov)
  • 1 Typically, genomic integrity is protected by a series of processes, including DNA damage repair, cell cycle checkpoints, and apoptosis. (dovepress.com)
  • Aberrant expression of circadian clock genes could have important consequences on the transactivation of downstream targets that control the cell cycle and on the ability of cells to undergo apoptosis. (biomedcentral.com)
  • Apoptosis is programmed cell death characterized by the activation of catabolic enzymes, which is responsible for degradation of cellular components, shrinkage of the cell, condensation of chromatin and fragmentation of DNA [ 4 , 5 ]. (ijpsonline.com)
  • It has been proved that multiple types of cancer including breast cancer are developed due to malfunctioning of the genes, which code antiapoptotic proteins, apoptosis inhibitors or tumor suppressors [ 6 , 7 ]. (ijpsonline.com)
  • Since p53 was identified as a tumor suppressor protein in late 1980's, various studies have focused on its contributions on cell cycle arrest, senescence, apoptosis and autophagy [ 8 , 9 ]. (ijpsonline.com)
  • Thus DOX inhibits replication and transcription causing cell cycle arrest and apoptosis afterwards [ 16 ]. (ijpsonline.com)
  • More recent work has revealed that MMR proteins play an important role in cell cycle arrest and apoptosis in response to certain DNA damaging agents. (uchc.edu)
  • First, we are examining the cellular functions of the MMR proteins and the effects of cancer-causing missense mutations by studying how these mutant proteins perform in DNA repair, cell cycle checkpoint signaling, apoptosis signaling and other functional assays. (uchc.edu)
  • It is usually understood that carcinogenesis is a multistep process that involves defects of the genetic pathways including cell proliferation, cell adhesion, cell death and apoptosis [ 2 ]. (biomedcentral.com)
  • The tumor suppressor gene rules for the 220?kD nuclear phosphoprotein which includes been proven to be engaged in lots of cellular processes such as for example cell routine checkpoint control, DNA harm fix and recognition, apoptosis, the ubiquitin-proteasome pathway, and transcriptional regulation [7C10]. (imacst.com)
Pathways16
  • The goal is to identify key genes, enzymatic activities, components of signaling pathways, or cellular processes, which are altered in human cancer, as potential intervention points or targets that could be used in the design of new cancer drugs. (nih.gov)
  • For example, projects may include development of organisms in which genes in key pathways or processes are mutated or in which human transgenes are expressed to simulate changes known to occur in human cancers. (nih.gov)
  • Despite rigorous testing and design of epigenetic targeting agents, the mechanisms by which they act to modulate key cell growth regulatory pathways remain unclear. (mayo.edu)
  • Even as the nature of the exact cell in which Merkel cell carcinoma oncogenesis occurs is controversial, there is strong support for the notion that Merkel cell carcinoma results from of one of two distinct pathways. (medscape.com)
  • Specifically, it regulates the organization of apical plasma membrane in epithelial cells, disk morphogenesis during early retinal development, MAPK and Akt signaling pathways, and in cholesterol metabolism. (nih.gov)
  • Accordingly, entry into S-phase is controlled by molecular pathways that facilitate a rapid, unidirectional shift in cell state. (wikipedia.org)
  • These responses are elicited through signalling pathways, which activate cell cycle checkpoints and basically lead to three cellular fates: cycle arrest promoting DNA repair, senescence (permanent arrest) or cell death. (biomedcentral.com)
  • Here, we advance a qualitative model covering DNA damage response pathways, focusing on G1/S checkpoint enforcement, supposedly more sensitive to arrest than G2/M checkpoint. (biomedcentral.com)
  • We define a discrete, logical model encompassing ATM (ataxia telangiectasia mutated) and ATR (ATM and Rad3-related) pathways activation upon DNA damage, as well as G1/S checkpoint main components. (biomedcentral.com)
  • As a step towards an integrative model of DNA-damage response pathways to better cover the onset of senescence, our model focuses on G1/S checkpoint enforcement. (biomedcentral.com)
  • Figure 1 below schematically illustrates a summary of the TOR signaling pathways in mammalian cells under nutrient replete and restricted conditions, and under rapamycin treatment. (nih.gov)
  • These Cdk1/Cdc2 regulators are the downstream targets of two well-characterized G2/M checkpoint pathways which prevent cells from entering mitosis when cellular DNA is damaged or when DNA replication is inhibited. (reactome.org)
  • However, IR-induced DNA damage also triggers DNA damage response (DDR) signaling pathways in cells. (biomedcentral.com)
  • Tumor microenvironment (TME) Oncology research solutions TABLE OF CONTENTS Molecular drivers of cancer pathogenesis Cancer progression is associated with the interplay between tumor cells and the surrounding environment, which requires signal transduction pathways to relay messages throughout the cell.1,2 Cell signaling pathways regulate everything from cell growth to proliferation to survival. (technologynetworks.com)
  • Finally, downstream nuclear targets of signaling pathways like the transcription factors Myc and NF-κB, chromatin remodelers, and cell cycle effectors are also commonly altered. (technologynetworks.com)
  • Many of the genes commonly mutated encode Purpose and scope INTRODUCTION components or targets of the PI3K/AKT and Ras/ERK pathways, causing dysregulation of cellular signaling.1 This dysregulation drives cancer progression by influencing the behavior of tumor cells through cell proliferation, survival, migration, differentiation, metabolism, polarity, angiogenesis, and the tumor microenvironment. (technologynetworks.com)
Mutations16
  • Germline mutations of the breast cancer associated gene 1 (BRCA1) predispose women to breast and ovarian cancers. (nih.gov)
  • Neonatal hypotonia, developmental delay, encephalopathy, with seizures, deafness and lactic acidosis have been associated with mutations in this gene. (wikipedia.org)
  • Mutations in this gene have been shown to cause progressive external ophthalmoplegia. (wikipedia.org)
  • Projects could focus on validating inferences already drawn from comparative study of cancerous and normal cells, exploring promising leads from the nature of mutations known to be associated with cancer development, or testing hypotheses generated by the identification of new and unknown gene products, such as those sequenced through the NCI's Cancer Genome Anatomy Project (CGAP) . (nih.gov)
  • Mutations of this gene are associated with Seckel syndrome. (genetex.com)
  • Their checkpoints aren't fully developed, so they might continue to develop even with severe mutations. (singularityhub.com)
  • Our studies also revealed that free Lap induces gene mutations in Salmonella Typhimurium, nevertheless, the complexes demonstrated the absence of genotoxicity by the Ames test. (bvsalud.org)
  • Mutations occur randomly and are selected for in cellu- point mutations caused by the mutator gene during lar clonal evolution. (nih.gov)
  • A range of model perturbations corresponding to gene loss-of-function or gain-of-function is compared to experimental mutations. (biomedcentral.com)
  • The aim of this work is to study p53 gene mutations (exon7) as a new early diagnostic marker of HCC in Egyptian patients. (madridge.org)
  • All groups will be subjected to history taking, clinical examination, abdominal ultasonography with or without triphasic CT scanning, routine laboratory investigations, alpha fetoprotien, hepatitis viral markers and detection of mutations in exon 7 of p53 gene by PCR-RFLEP followed by confirmatory direct DNA sequencing. (madridge.org)
  • The most common hereditary disease that predisposes patients to colorectal cancer is Lynch syndrome (LS) which stems from mutations in the mismatch repair (MMR) genes. (uchc.edu)
  • Most recently, we have begun to characterize the function of the MMR pathway in human pluripotent stem cells and are using CRISPR/Cas9 gene targeting approaches to introduce missense mutations into the endogenous MMR gene loci. (uchc.edu)
  • The research in my laboratory involves an array of techniques from cell biology to molecular genetics to genomics to address the fundamental question of why mutations in DNA mismatch repair genes cause cancer. (uchc.edu)
  • We are predominantly interested in using cancer-associated missense mutations of the MSH2 and MSH6 genes to understand the functions of mismatch repair affected during colorectal tumorigenesis. (uchc.edu)
  • These mutations can either activate genes or result in loss of function. (technologynetworks.com)
Proteins14
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • Current clinically important drugs act as cytotoxic agents by binding to or damaging DNA, altering cellular mechanisms, or binding to structural proteins such as tubulin causing disruption of cell function. (nih.gov)
  • This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (genetex.com)
  • It cleaves the membrane-bound precursor of TUMOR NECROSIS FACTOR-ALPHA between ALANINE 76 and VALINE 77 to its functional form, as well as several other CELL SURFACE PROTEINS to their soluble forms, including AMYLOID BETA-PROTEIN PRECURSOR and PRION PROTEIN. (nih.gov)
  • HN - 2017 MH - ADAM12 Protein UI - D000072199 MN - D8.811.277.656.675.374.102.125 MN - D9.400.430.500.125 MN - D12.776.395.33.125 MS - A disintegrin and metalloproteinase domain-containing protein that is expressed as two alternatively-spliced forms: a long transmembrane form (ADAM12-L) and a short soluble form (ADAM12-S). It modulates the cleavage of INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS and may also regulate CELL FUSION during MYOGENESIS. (nih.gov)
  • In contrast to ADAM proteins, which reside on CELL MEMBRANES, ADAMTS proteases are secreted and function in the EXTRACELLULAR MATRIX. (nih.gov)
  • Circadian genes and the proteins produced by these genes constitute the molecular components of the circadian oscillator which form positive/negative feedback loops and generate circadian rhythms. (biomedcentral.com)
  • Clinical proteomics holds the potential of taking a snapshot of the total protein complement of a cell, or body fluid, and identifying proteins as potential biomarkers for the differentiation of disease and health [ 1 ]. (biomedcentral.com)
  • a member of the MRN complex , composed of Mre11, Rad50, and Nbs1), BRCA1, and SMC1 (structural maintenance of chromosomes), and these proteins coordinate repair with the cell cycle. (oncohemakey.com)
  • Genetic alterations to cellular genes may be inherited or arise spontaneously because of DNA damage from an environmental carcinogen or mutation from replication errors.1 Many common genetic lesions in cancer involve signaling proteins. (technologynetworks.com)
  • The aim of our study was to evaluate survival outcomes in malignant mixed Mullerian tumors (MMMT) of the uterus with respect to the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components. (biomedcentral.com)
  • Cell survival and apoptotic regulatory proteins such as the Bcl-2 family of genes, PCNA, p16, p21, p27, and cyclin D1 are of vital importance to malignant neoplasms in prolonging cell survival. (biomedcentral.com)
  • The aim of this study is to evaluate the role of cell cycle and apoptotic regulatory proteins in the carcinomatous and sarcomatous components of uterine MMMT in relation to clinico-pathological data including survival outcomes. (biomedcentral.com)
  • Also immunohistochemistry (IHC) tests were perform to investigate the proteins expression of P53 gene as well as high HPV oncogenes E6 and E7 in benign and malignant laryngeal tumors. (pdfplayer.org)
Kinase10
  • Another important class of tumor suppressor genes involved in cell cycle control and in the generation of human cancers is the cyclin-dependent kinase (CDK) inhibitors. (medscape.com)
  • Red No. 3, beta-estradiol, and DDT increase ER site-specific DNA binding to the estrogen response element in HTB 133 cells and increase cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells. (researchgate.net)
  • We further show that the deaminase ADAL preferentially catabolizes N 6 -methyl-2'-deoxyadenosine monophosphate (6mdAMP) in vitro and in vivo , and adenylate kinase 1 restricts the phosphorylation rate of 6mdAMP, together contributing to the identified checkpoint. (researchsquare.com)
  • The protein encoded by this gene belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. (genetex.com)
  • In yeast, for instance, cell growth induces accumulation of Cln3 cyclin , which complexes with the cyclin dependent kinase CDK2. (wikipedia.org)
  • Although ATM kinase activation is dependent on DSB damage generation, it can also occur following oxidative stress [3, 10]. (cahrr.org)
  • As ATLD and AT patients show similar neurodegeneration phenotypes, we hypothesized that ATLD cells harbor defects in ATM kinase and that MRE11 may be important for ATM activation upon oxidative stress. (cahrr.org)
  • Progression of cells from G2 phase of the cell cycle to mitosis is a tightly regulated cellular process that requires activation of the Cdk1/Cdc2 kinase, which determines onset of mitosis in all eukaryotic cells. (reactome.org)
  • The carbon source dependent regulation of Rnr3 is mediated by Mec1, the budding yeast ATM/ATR checkpoint response kinase. (microbialcell.com)
  • Mec1 is an ATM/ATR protein, a family of conserved phosphatidylinositol 3-kinase like kinases (PIKKs) best understood for their roles in mediating the DNA damage response (DDR) [5] . (microbialcell.com)
Cellular9
  • Thus BRCA1 mutant cells cannot develop further into full-grown tumors unless this cellular defense is broken. (nih.gov)
  • Site-specific DNA binding by p53 in RLE, HTB 125, HTB 133, and MCF-7 cells was increased when they were treated with Red No. 3, which suggests that cellular DNA was damaged by this colorant. (researchgate.net)
  • DNA damage (single or double-strand breaks) triggers adapted cellular responses. (biomedcentral.com)
  • The mechanisms responsible for this decay are both cell intrinsic, such as cellular senescence, as well as cell-extrinsic, such as changes in the regenerative environment. (mdpi.com)
  • PIK-related kinases are involved in diverse cellular functions including cell growth, cell cycle, DNA damage checkpoints, recombination, and telomere maintenance. (nih.gov)
  • Regulation RNAPII transcription of genes important in cellular response to changes in nutrient conditions, such as nitrogen levels (Rohde et al. (nih.gov)
  • Although some aspects of Vpr-induced G2/M arrest resembles induction of host cellular checkpoints, increasing evidence suggests that Vpr induces cell cycle G2 arrest through a mechanism that is to some extent different from the classic G2/M checkpoints. (reactome.org)
  • The biological basis for the therapeutic effects of RT is that the applied ionizing radiation (IR) causes lethal double-strand breaks in the cellular DNA leading to tumor cell death. (biomedcentral.com)
  • Depletion of RNASEH2 Activity Leads to Accumulation of DNA Double-strand Breaks and Reduced Cellular Survivability in T Cell Leukemia. (nih.gov)
Tumors4
  • Although carcinogenic roles for the INK4B, INK4C, INK4D, CIP1, KIP1, and KIP2 genes appear to be limited, INK4A is among the most commonly mutated genes in human tumors. (medscape.com)
  • Also see Merkel Cell Tumors of the Head and Neck and Merkel Cell Carcinoma and Rare Appendageal Tumors . (medscape.com)
  • This method among tumors, elucidating this information can be impor- also identifies mutator genes that induce increase of tant for understanding tumorigenesis. (nih.gov)
  • Despite the understanding that cell cycle regulatory protein dysregulation may be involved in numerous malignant tumors [ 2 ], there is limited data that explores the role of these oncoproteins with survival data in MMMTs. (biomedcentral.com)
Aberrant4
  • In both mechanisms, similar events occur: DNA breakage, aberrant cell migration, and complex biological changes that cause the abnormal crystalline protein to fold, and unregulated lens cell morphology. (wepapers.com)
  • Aberrant silencing of tumor suppressor genes (the p16 gene in this example) by promoter DNA hypermethylation and chromatin compaction. (mayo.edu)
  • Schematic structure of the p16 tumor suppressor gene locus indicating the progression to aberrant promoter DNA hypermethylation and recruitment of chromatin remodelers that put the gene in a silent state. (mayo.edu)
  • In its regular state, BRCA1 features being a tumor suppressor gene, inhibiting the aberrant proliferation of tumor cells. (imacst.com)
Progression6
  • Mounting evidence indicates that BRCA1 is involved in all phases of the cell cycle and regulates orderly events during cell cycle progression. (nih.gov)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • Despite its low abundance, eukaryotic DNA 6mA has a number of potential functions regulating gene transcription 5 , 8 , transposon activity 9 , 10 , 16 , nucleosome occupancy 6 , 17 , 18 , and transgenerational progression 19 - 22 . (researchsquare.com)
  • also comprises p53 together with cell cycle regulation allowing to investigate the impact of DNA damage intensities on cell cycle progression [ 14 ]. (biomedcentral.com)
  • Progression of the cell cycle devoid of resolution from the dilemma triggers genome instabilities and cell death. (jakenzyme.com)
  • HR-HPV DNA integration into host cells chromosome, predominately for HPV 16/18/31/33/45/53 subtypes , altered epithelial cells DNA by inhibiting tumor suppressor genes p53 and Rb, resulting in increased viral replication and tumor progression ( 7,8). (pdfplayer.org)
Replication11
  • Throughout M phase and G1 phase, cells assemble inactive pre-replication complexes (pre-RC) on replication origins distributed throughout the genome. (wikipedia.org)
  • [4] During S-phase, the cell converts pre-RCs into active replication forks to initiate DNA replication. (wikipedia.org)
  • All eukaryotes possess many more replication origins than strictly needed during one cycle of DNA replication. (wikipedia.org)
  • [5] Redundant origins may increase the flexibility of DNA replication, allowing cells to control the rate of DNA synthesis and respond to replication stress. (wikipedia.org)
  • The G1/S and intra-S phase checkpoints inhibit the replication of damaged DNA and work in a coordinated manner with the DNA repair machinery to permit the restitution of DNA integrity, thereby increasing cell survival. (oncohemakey.com)
  • 1996), which modulates host cell cycle machinery to benefit viral survival or replication. (reactome.org)
  • While Rnr1 is required for DNA replication and DNA damage repair, the function(s) of Rnr3 is unknown. (microbialcell.com)
  • Rnr3, on the other hand, is detectable only under the condition of DNA damage or replication stress [3] . (microbialcell.com)
  • The latter are ATM/ATR targets, which become activated in response to replication stress and DNA damage, respectively [5] [12] . (microbialcell.com)
  • Rad53 is phosphorylated in response to both replication stress (i.e like CHK1) and DNA damage (i.e. like CHK2) in a Mec1 dependent manner. (microbialcell.com)
  • The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. (nih.gov)
Pathway7
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • The complexes induced an increase in the reactive oxygen species, and the co-treatment with N-acetyl-L-cysteine remarkably suppressed the ROS generation and prevented the reduction of cell viability, suggesting that the cytotoxicity of the complexes is related to the ROS-mediated pathway. (bvsalud.org)
  • [3] Since upregulation of S-phase genes drive further suppression of Whi5 , this pathway creates a positive feedback loop that fully commits cells to S-phase gene expression. (wikipedia.org)
  • Consequently it was concluded that doxorubicin directly influences apoptotic pathway and multidrug resistance in both MCF-7 and MDA-MB-231 cells even though data all together suggest that the effect is more significant on MDA-MB-231. (ijpsonline.com)
  • Therefore, expression levels of p53 and other genes in p53 pathway have major role on cancer development [ 11 ]. (ijpsonline.com)
  • Cell viability percentages, cell cycle phases, which cells were on, apoptotic cell rates, drug efflux levels via P-gp, expression levels of Mdr-1 as well as certain genes in p53 apoptotic pathway were measured. (ijpsonline.com)
  • Our study supports that a) cell cycle and apoptotic regulatory protein dysregulation is an important pathway for tumorigenesis and b) p53 is an important immunoprognostic marker in MMMT of the uterus. (biomedcentral.com)
Genetic7
  • The genotoxic action of contaminating agents affects human health directly, damaging the genetic material, which is considered to play an important role in oncogenesis [6,7]. (researchgate.net)
  • On the other hand, it has been reported that exposure to some xenoestrogens and to estrogenic metabolites promotes the production of free radicals through the hydrogen peroxide (H 2 O 2 ) reduction cycle, by means of the P 450 oxidase and reductase enzymes, giving origin to the production of oxygen reactive species which might damage the genetic material [33]. (researchgate.net)
  • The genotoxicity of some environmental contaminants may affect human health directly by damaging genetic material and thus plays an important role in cancer development. (researchgate.net)
  • To address these questions, we are identifying groups of co-expressed and co-regulated genes from our scRNA-seq data, associating them with the cell biology that occurs in their respective cell types, comparing their use across tissues, and using reverse genetic and imaging approaches to determine their function. (nih.gov)
  • These genetic manipulations could present a "proof of principle" or validation of the importance of the target genes to the development of cancer. (nih.gov)
  • When the cell cycle proceeds without control, cells can divide without order and accumulate genetic errors that can lead to a cancerous tumor . (medlineplus.gov)
  • TOR (target of rapamycin) was originally identified in yeast genetic screens as two genes ( Tor1 and Tor2 ). (nih.gov)
Proliferation4
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • Moreover, in adults, Merkel cells undergo slow turnover and are replaced by cells originating from epidermal stem cells, not through the proliferation of differentiated Merkel cells. (medscape.com)
  • Thus, a reasonable therapeutic option is certainly to revive the tumor suppressor function of BRCA1 in cancers cells to be able to suppress cell proliferation. (imacst.com)
  • Within a cell lifestyle model, a standard splice variant of BRCA1 was overexpressed with a retroviral vector leading to reduced cell proliferation. (imacst.com)
Regulation9
  • Studies of growth regulation, cell cycle control, or other basic studies that are not explicitly focused on tumor target cell systems may receive primary assignment within the NIGMS or another institute. (nih.gov)
  • Our data revealed up-regulation of 1015 genes and down-regulation of 1207 genes in the polyploid populations, as compared to the non-polyploid group. (plos.org)
  • Comparative RT-PCR and in situ hybridization results indeed confirmed differential expressional regulation of several genes between the two populations. (plos.org)
  • The inhibition of mitochondrial activity by various pharmacological inhibitors, as well as by gene-specific targeting using siRNA-mediated technology showed a dramatic attenuation of polyploidy and bi-nucleation development during in vitro stromal cell decidualization, suggesting mitochondria play a major role in positive regulation of decidual cell polyploidization. (plos.org)
  • Tight regulation of this process ensures that a dividing cell's DNA is copied properly, any errors in the DNA are repaired, and each daughter cell receives a full set of chromosomes. (medlineplus.gov)
  • Disruption of normal regulation of the cell cycle can lead to diseases such as cancer. (medlineplus.gov)
  • The circadian regulation extends beyond clock genes to involve various clock-controlled genes (CCGs) including various cell cycle genes. (biomedcentral.com)
  • Thus an in-depth understanding of the molecular mechanisms underlying Vpr-induced G2 arrest will provide additional insights into the basic biology of cell cycle G2/M regulation and into the biological significance of this effect during host-pathogen interactions. (reactome.org)
  • Unexpectedly, this regulation is independent of all currently known components of the Mec1 DNA damage response network, including Rad53, Dun1, and Tel1, implicating a novel Mec1 signalling axis. (microbialcell.com)
Regulates2
  • In addition to increasing transcription of histone genes, S-phase entry also regulates histone production at the RNA level. (wikipedia.org)
  • P53, also known as TP53 or tumor protein is a gene that codes for a protein that regulates the cell cycle and hence functions as a tumor suppression [10] . (madridge.org)
Genome integrity1
  • Functional analysis of BRCA1 in cell cycle checkpoints, genome integrity, DNA damage response (DDR) and tumor evolution should benefit our understanding of the mechanisms underlying BRCA1 associated tumorigenesis, as well as the development of therapeutic approaches for this lethal disease. (nih.gov)
BRCA14
  • BRCA1 deficiency, consequently causes abnormalities in the S-phase checkpoint, the G(2)/M checkpoint, the spindle checkpoint and centrosome duplication. (nih.gov)
  • Once in its phosphorylated condition, BRCA1 becomes component of a variety of complexes which relocate to regions of broken DNA and organize cell routine checkpoints to be able to execute DNA fix. (imacst.com)
  • Gene Therapy The initial efforts to focus on BRCA1 in EOC included rebuilding BRCA1 function via gene therapy [12]. (imacst.com)
  • In the Stage I trial, twelve sufferers with repeated metastatic ovarian cancers, who was simply treated with regular medical operation and chemotherapy, received one to three cycles of intraperitoneal injections of BRCA1 in a retroviral vector. (imacst.com)
Apoptotic2
  • Apoptotic cell number increased in MCF-7 and Bax/Bcl-2 ratio was measured to be ~ 7 fold higher in cells treated with 200 nM of doxorubicin when compared to the control. (ijpsonline.com)
  • Likewise, apoptotic cell rate increased in MDA-MB-231 cells and Bax/Bcl-2 ratio was increased by 2 fold compared to the control. (ijpsonline.com)
Epithelial9
  • The pesticide DDT and the food colorant Red No. 3 were found to increase the growth of HTB 133 but not estrogen receptor (ER) negative human breast cells (HTB 125) or rat liver epithelial cells (RLE). (researchgate.net)
  • the comet assay in peripheral blood-isolated lymphocytes and mammary epithelial cells was also carried out. (researchgate.net)
  • Our results suggest that DDT is genotoxic, not only for lymphocytes but also to mammary epithelial cells. (researchgate.net)
  • With the advent of improved immunohistochemical profiling, the tumor was reclassified as Merkel cell carcinoma because shared epithelial and neuroendocrine markers, along with ultrastructural features suggestive of neural crest origin, were observed in both the constituent tumor cell and the physiologic Merkel cell of the skin. (medscape.com)
  • Within skin, Merkel cells have also been shown to cluster in the basal layers of the interfollicular epidermis in specialized epithelial structures called touch domes, where they are juxtaposed with epidermal keratinocytes. (medscape.com)
  • [ 5 , 6 ] Furthermore, experiments have demonstrated that epidermal progenitors in the touch domes are capable of producing Merkel cell lines and that epithelial progenitor populations in adults have the capacity to give rise to both neuroendocrine and squamous lineages. (medscape.com)
  • Other suggested cells of origin include the neural crest‒derived cell of amine precursor uptake and decarboxylation (APUD) system, dermal fibroblasts, pre or pro B cells, residual epidermal stem cells, and epithelial, non-Merkel cell progenitors. (medscape.com)
  • Caco-2 (human colorectal adenocarcinoma), and against two non-cancer cells, FGH (human gingival normal fibroblasts) and PNT-2 (prostate epithelial cells). (bvsalud.org)
  • MH - A549 Cells UI - D000072283 MN - A11.251.210.190.80 MN - A11.251.860.180.80 MN - A11.436.54 MS - An immortalized cell line derived from human ADENOCARCINOMA, ALVEOLAR basal epithelial cells isolated from the lungs of a male patient in 1972. (nih.gov)
Tumor cells4
  • These changes can be inherited and are, therefore, found in every cell, but more often, they are somatically acquired and restricted to tumor cells. (medscape.com)
  • This study aimed to evaluate Attalea funifera seed oil with or without resveratrol entrapped in organogel nanoparticles in vitro against A375 human melanoma tumor cells. (bvsalud.org)
  • One study looked at a PARP-1 inhibitor, 3-aminobenzamide, and found increased cisplatin cytotoxicity in CH1cisR cisplatin-resistant ovarian tumor cells [18]. (imacst.com)
  • Furthermore, when Calu-6-NSCLC tumor cells were implanted into a nude mouse model, there was a 35% reduction in tumor growth with CEP-6800/cisplatin combination treatment compared to single-agent cisplatin. (imacst.com)
Transcription5
  • As a transcription factor whose expression is increased by DNA damage, p53 blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)
  • My second post-doctoral position was in Prof Nic Jones' laboratory and focussed upon the control of cell cycle-dependent transcription. (ncl.ac.uk)
  • [3] The Cln3-CDK2 complex promotes transcription of S-phase genes by inactivating the transcriptional repressor Whi5 . (wikipedia.org)
  • [3] Active cyclin D-CDK4/6 complex induces release of E2F transcription factor, which in turn initiates expression of S-phase genes. (wikipedia.org)
  • If irradiated cells have already passed the restriction point, a position in G1 phase that is regulated by the phosphorylation of the retinoblastoma tumor suppressor gene ( Rb ) and its dissociation from the E2F family of transcription factors, they will transiently arrest in S phase. (oncohemakey.com)
Retinoblastoma tumor supp1
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
Kinases1
Processes4
  • My laboratory studies how the modulation of chromatin is used by eukaryotic cells to regulate fundamental processes such as gene expression and genome stability. (ncl.ac.uk)
  • [1] Since accurate duplication of the genome is critical to successful cell division, the processes that occur during S-phase are tightly regulated and widely conserved. (wikipedia.org)
  • Differences in the functioning of these processes in different cells or under different conditions determine the final effect of a certain dose of IR [ 5 ]. (biomedcentral.com)
  • In this review article, we focus on the critical functions of AHR for DNA damage-dependent processes and immune responses which may contribute to the development of SCC in chronically UV- and/or PAH-exposed skin. (frontiersin.org)
Target genes1
  • [3] Several E2F target genes promote further release of E2F, creating a positive feedback loop similar to the one found in yeast. (wikipedia.org)
Arrest8
Embryos5
  • The cell-cycle checkpoint protein p53 both directs terminal differentiation and protects embryos from DNA damage. (nih.gov)
  • How do cell in early embryos cope with DNA damage? (nih.gov)
  • We've found that cells in early zebrafish embryos transcribe an unusual group of genes in response to DNA damage and seem to exhibit a bias in the downstream cell types they can differentiate into. (nih.gov)
  • We can already edit genes in human embryos. (singularityhub.com)
  • In embryos, however, cells aren't nearly as altruistic. (singularityhub.com)
Phenotypes2
  • However, the genes involved in cell cycle checkpoints and DSB repair are not accountable for the neurodegeneration phenotypes. (cahrr.org)
  • Collectively, evidence suggests that the oxidative stress caused by ATM function defects might lead to neurodegeneration phenotypes in AOA3 cells. (cahrr.org)
Genomic instability1
  • This method also identifies mutator genes which increase genomic instability when they are altered and provides estimates of the increased rate of alterations caused by each mutator gene. (nih.gov)
Histone1
Molecular4
  • How does the embryo regulate the tiny molecular machines that transform cells? (nih.gov)
  • Collectively, analyses of unique polyploidy markers and molecular signaling networks may be useful to further characterize functional aspects of decidual cell polyploidy at the site of implantation. (plos.org)
  • P53 gene mutation (G to T codon 249) may be regarded as an early molecular marker in the detection of HCC in Egyptian patients. (madridge.org)
  • Protein isoforms are an essential mechanism employed by human cells to enhance molecular functional diversity encoded by the genome. (biomedcentral.com)
Methylation1
  • DNMT1 (green staining) colocalizes with DNA double strand breaks and is detected using gamma H2AX as a marker (red staining) in cells treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine (5-azadC). (mayo.edu)
Instability1
  • Indeed, defects in chromatin are associated with gene dysregulation, genome instability and a number of diseases states that include cancers and neurodegenerative disorders. (ncl.ac.uk)
Induce2
  • By heavy stable isotope tracing, we demonstrate that intracellular degradation of RNA m6A cannot induce any misincorporated DNA 6mA, unveiling the existence of a catabolism checkpoint that blocks DNA 6mA misincorporation. (researchsquare.com)
  • Furthermore, a low oxygen environment would also protect cells from x-ray-induced damage because there would be fewer radicals available to induce DNA damage in the absence of oxygen, but this environment would have little impact on DNA damage induced by carbon nuclei. (oncohemakey.com)
Mammalian cells1
  • A remarkably similar regulatory scheme exists in mammalian cells. (wikipedia.org)
Restriction3
  • Entry into S-phase is controlled by the G1 restriction point (R), which commits cells to the remainder of the cell-cycle if there is adequate nutrients and growth signaling. (wikipedia.org)
  • after passing the restriction point, the cell will progress through S-phase even if environmental conditions become unfavorable. (wikipedia.org)
  • The cell cycle has checkpoints (also called restriction points), which allow certain genes to check for problems and halt the cycle for repairs if something goes wrong. (medlineplus.gov)
Proto-oncogenes3
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • This article briefly discusses tumor suppressor genes and then focuses on the role of proto-oncogenes in childhood cancer. (medscape.com)
  • Some examples of genes that are well studied in model organisms and known or strongly suspected of involvement in cancer include oncogenes, proto-oncogenes, some cell cycle and signal transduction genes, and DNA repair genes. (nih.gov)
Functional2
  • Genes involved in cell cycle checkpoints are remarkably conserved in many organisms, but a few lines of evidence indicate functional differences among organisms. (jakenzyme.com)
  • Multidrug resistance (MDR) is a term used to define resistance of the cells against multiple drugs, which may or may not be similar in structural or functional basis and is one of the main reasons why attempts of using anticancer agents in cancer therapy fails [ 12 - 14 ]. (ijpsonline.com)
Transcriptional2
  • What genes drive these decisions, and how stereotyped are these transcriptional cascades across cells that adopt a similar fate? (nih.gov)
  • To address these questions, we are combining single-cell transcriptomics, transgenic reporters, and CRISPR/Cas9 mutagenesis to track the behavior and fate of damaged cells and to determine the function of their pre-gastrulation transcriptional response to DNA damage. (nih.gov)
Organisms1
  • The circadian timing system proficiently coordinates the physiology of living organisms to match environmental or imposed 24-hour cycles [ 3 ]. (biomedcentral.com)
Viability3
  • Guo and but might be indispensable for the viability of neural cells in the cerebellum. (cahrr.org)
  • Assay performance was compared to that of the CFA and the CellTiter-Blue homogeneous uniform-well cell viability assay. (biomedcentral.com)
  • On 4 different cancer cell lines, the automated cell counting assay produced radiation dose response curves that followed a linear-quadratic equation and that exhibited a better correlation to the results of the CFA than did the cell viability assay. (biomedcentral.com)
Inhibit1
  • For example, 5-azadC is known to inhibit DNA methyltransferases and in dividing cells lead to demethylation of aberrantly hypermethylated tumor suppressor genes. (mayo.edu)
Phosphorylate1
  • In response to DNA damage, activated ATM can directly phosphorylate p53 and mdm2, the ubiquitin ligase that targets p53 for degradation. (oncohemakey.com)
Expression9
  • Increased expression of RRM2B has been correlated with gemcitabine resistance in human cholangiocarcinoma cells and may be predictive of lack of clinical benefit from gemcitabine for human cancers. (wikipedia.org)
  • During development, external and intrinsic cues drive cascades of gene expression within cells that direct them to become particular cell types. (nih.gov)
  • We recently developed an approach to reconstruct developmental gene expression trajectories from thousands of single-cell transcriptomes. (nih.gov)
  • This lets us track which genes are expressed as cells are specified into different cell types and to investigate how stereotyped those expression patterns are. (nih.gov)
  • Differential gene expression between Gsr-WT and Gsr-KO lungs was analyzed at discrete developmental stages. (northwestern.edu)
  • Analysis of ATP-Binding Cassette Transporter Expression in Drug-Selected Cell Lines by a Microarray Dedicated to Multidrug Resistance. (nih.gov)
  • Is the Gene Expression Pattern of Lung Cancer Detected by Screening With Spiral Computed Tomography Different from That of Symptom-Detected Lung Cancer? (nih.gov)
  • Further analyses of genes that are related to mitochondria and bi-nucleation showed differential and regional expression within the decidual bed, consistent with the pattern of polyploidy. (plos.org)
  • Drug efflux assay results were also shown to be consistent with Mdr-1 gene expression levels in both cell lines. (ijpsonline.com)
Response to DNA damage2
  • Why is there a specific response to DNA damage before gastrulation, and why does it include developmental regulators? (nih.gov)
  • 4 In response to DNA damage, H2AX is rapidly phosphorylated by ATM and localizes to sites of DNA double-strand breaks in multiprotein complexes described as foci ( Fig. 13.4 ). (oncohemakey.com)
Squamous cell carc1
  • Cutaneous squamous cell carcinoma (SCC) is one of the most frequent malignancies in humans and academia as well as public authorities expect a further increase of its incidence in the next years. (frontiersin.org)
Chromosome3
  • The gene encoding the RRM2B protein is located on chromosome 8, at position 8q23.1. (wikipedia.org)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • DNA damage consists of DNA single-strand breaks (SSB) and double-strand breaks (DSB) that present a threat to structural chromosome stability and are thus the main inducers of DNA damage response [ 2 ]. (biomedcentral.com)
Phosphorylation1
  • Furthermore, we reported that AOA3-patient cells showed excessive accumulation of ROS (reactive oxygen species), particularly the mitochondria-related ROS superoxide, which perturbed ATM-dependent phosphorylation [8, 9]. (cahrr.org)
Mechanisms3
  • Another controversial issue involves the causative mechanisms of radiation damage. (wepapers.com)
  • 2008). Radiation damage occurs through two mechanisms: direct and oxidative (Shore, Neriishi & Nakashima, 2010). (wepapers.com)
  • The mechanisms underlying radioresistance of cancer cells are incompletely understood. (biomedcentral.com)
Integrity1
  • The AHR is expressed in all cutaneous cell-types investigated so far and maintains skin integrity. (frontiersin.org)
Mitosis1
CRISPR4
  • CRISPR as a gene editor is getting more specific and efficient by the day, they explained. (singularityhub.com)
  • The big one: we're still trying to tease out how CRISPR works in cells that form the embryo, in hopes that we can cut down on potential mistakes. (singularityhub.com)
  • The way CRISPR works heavily depends on the cell cycle. (singularityhub.com)
  • What we call "gene editing" is the cell's DNA repair system kicking into high gear, trying to patch up the mess CRISPR left behind. (singularityhub.com)
Radiation6
  • It has been accepted that cataractogenic radiation damage occurs either by direct or oxidative mechanism (Shore, Neriishi & Nakashima, 2010). (wepapers.com)
  • However, Sliney (1986) noted that direct damage (e.g. by direct ultraviolet radiation [UVR]) has very limited value due to the fact that most 300-nm UVR exposure upon the crystalline lens is indirect and scattered even at the peak irradiance period between 9:00 a.m. and 3:00 p.m. (wepapers.com)
  • This means that, apart from the controversial probability of direct radiation damage, an indirect mechanism had been involved in RCG. (wepapers.com)
  • Radiation is administered to cells either in the form of photons (x-rays and gamma rays) or particles (protons, neutrons, and electrons). (oncohemakey.com)
  • At present only a handful of genes have been described to play a role in the radiation response. (biomedcentral.com)
  • Accordingly, a chronic exposure to artificial (tanning beds) or solar UVB radiation and the associated accumulation of damaged keratinocytes is the most important risk factor for SCC ( 1 - 3 ). (frontiersin.org)
Repair5
  • The version of R2 encoded by RRM2B is induced by p53, and is required for normal DNA repair and mtDNA synthesis in non-proliferating cells. (wikipedia.org)
  • 2 The incorporation of errors during DSB repair may lead to chromosomal rearrangements, such as translocation and deletion, which lead to proto-oncogenic transformations or cell death. (dovepress.com)
  • Aprataxin, the product of the gene causing AOA1, participates in DNA single-strand break repair [5, 6] while senataxin, the gene product responsible for AOA2, is crucial to resolve DNACRNA hybrid formation (R-loop) in transcript-related DNA damage [7]. (cahrr.org)
  • Using cell culture models including human pluripotent stem cells to study the functions of mutant MSH2 and MSH6 in damage repair and response. (uchc.edu)
  • These include genes involved in cell cycle checkpoint activation and DNA repair, such as e.g. (biomedcentral.com)
Abnormal2
  • Gsr-dependent, hyperoxia-responsive genes were highly associated with abnormal cytoskeleton, skeletal-muscular function, and tissue morphology at PND5. (northwestern.edu)
  • In AOA3, is mutated, and the patient-derived cells show abnormal mitochondrial dynamics [8, 9]. (cahrr.org)
Abstract1
  • A free radical generated through the interaction of photons with other molecules that possess an unpaired electron in their outermost shell (e.g., hydroxyl radicals) can abstract a hydrogen molecule from a macromolecule such as DNA to generate damage. (oncohemakey.com)
TP531
  • Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome who generally inherit a mutated TP53 gene from an affected parent. (medscape.com)
Double strand2
Abnormalities1
  • Abnormalities in this gene are one of the causes of mitochondrial DNA depletion syndrome (MDDS). (wikipedia.org)