AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Cell CycleCell Cycle ProteinsGenes, cdcCheckpoint Kinase 2DNA DamageMitosisG2 PhaseProtein-Serine-Threonine KinasesM Phase Cell Cycle CheckpointsCell Cycle CheckpointsMad2 ProteinsSpindle ApparatusProtein KinasesS PhaseAtaxia Telangiectasia Mutated ProteinsHydroxyureaDNA RepairNuclear ProteinsSaccharomyces cerevisiae ProteinsSchizosaccharomyces pombe ProteinsSchizosaccharomycesDNA ReplicationG2 Phase Cell Cycle CheckpointsKinetochoresFungal ProteinsDNA-Binding ProteinsSaccharomyces cerevisiaeMutationGamma RaysG1 PhaseChromosomal InstabilityGenes, FungalIntracellular Signaling Peptides and ProteinsTumor Suppressor Protein p53NocodazoleUltraviolet RaysPhosphorylationCdc20 ProteinsTumor Suppressor ProteinsDNA, Fungalcdc25 PhosphatasesCyclin BCDC2 Protein KinaseRadiation, IonizingS Phase Cell Cycle CheckpointsAneuploidyCalcium-Binding ProteinsGenomic InstabilityRepressor ProteinsHeLa CellsChromosome SegregationAtaxia TelangiectasiaMolecular Sequence DataCyclin-Dependent Kinase Inhibitor p21MetaphaseCyclin B1DNA Breaks, Double-StrandedCyclinsGene DeletionChromosomes, FungalCell DivisionCDC28 Protein Kinase, S cerevisiaeSignal TransductionApoptosisRadiation ToleranceAnaphaseG1 Phase Cell Cycle CheckpointsMethyl MethanesulfonateCell Line, TumorUbiquitin-Protein Ligase ComplexesAnaphase-Promoting Complex-CyclosomeCell LineBase SequenceModels, BiologicalHistonesChromosomal Proteins, Non-HistoneProtein BindingBRCA1 ProteinPhenotypeNeoplasm ProteinsAurora KinasesFibroblastsMicrotubulesRNA, Small InterferingCell NucleusAmino Acid SequenceFlow CytometryPrometaphaseCarrier ProteinsDNACentrosomeAllelesRetinoblastoma ProteinChromosomesCyclin-Dependent Kinase 2Cell SurvivalReplication Protein AChromatinMeiosisRNA Interference
MutationsApoptosisMitosisProgressionChromatinInhibitorsRegulationMutationTumor suppressorIsoformsTumorsRegulatorResponse to DNA damagePathwaysVariantsGenomeCancersRegulates cellMitoticOncogenesArrestChromosomesPrognosticDeletionNuclearSuggest that these proteinsProliferationTranscriptCentrosomeHomologous recombinationSequenceSerine threonTranscription factorPhenotypesMammalianKinase familyBRCA1ViralGroup of proteinsSpindleCancerTumourCellularExpressionNucleusControlMechanismsAbnormalitiesMultiple freeze-thaw cyclesDefectsHistoneMre11-Rad5PathwayDamageCHEK2Chromosome duplicationEssentialInterphaseRolesMalignanciesSomaticRepairExonsLocusCycB1
Mutations38
  • Mutations to the CHEK2 gene have been linked to a wide range of cancers. (wikipedia.org)
  • Inherited mutations in the CHEK2 gene have been linked to certain cases of breast cancer. (wikipedia.org)
  • Two more CHEK2 gene mutations, CHEK2*S428F, an amino-acid substitution to the kinase domain in exon 11 and CHEK2*P85L, an amino-acid substitution in the N-terminal region (exon 1) have been found in the Ashkenazi Jewish population. (wikipedia.org)
  • Most mutations in ATM result in truncation and destabilisation of the protein, but certain missense and splicing errors have been shown to produce a less severe phenotype. (bmj.com)
  • Frequent inactivating mutations of the ATM gene have been reported in patients with rare sporadic T cell prolymphocytic leukaemia (T-PLL), B cell chronic lymphocytic leukaemia (B-CLL), and most recently, mantle cell lymphoma (MCL). (bmj.com)
  • The presence of inactivating mutations, together with the deletion of the normal copy of the ATM gene in some patients with T-PLL, B-CLL, and MCL, establishes somatic inactivation of the ATM gene in the pathogenesis of lymphoid malignancies, and strongly suggests that ATM functions as a tumour suppressor. (bmj.com)
  • Multiple mutations affecting embryonic development have been induced by chemical and insertional mutagenesis resulting in the identification of genes with important roles in development in Drosophila [ 23 - 25 ]. (biomedcentral.com)
  • Altered levels of Tuberin and mutations in this protein have been found in several cancers, including medulloblastoma and skin cancer. (uwindsor.ca)
  • It is our hypothesis that these mutations can affect the Tuberin/CycB1 interaction and result in dysregulation of cell proliferation and cell size. (uwindsor.ca)
  • Having a better understanding of how specific changes in this large protein alters fundamental cell biology such as cell proliferation and cell size can ultimately help to effectively treat patients with these specific mutations. (uwindsor.ca)
  • About 8% of cases are hereditary, and approximately half of these are associated with germline mutations of the breast tumor suppressor gene BRCA1 (refs. (nih.gov)
  • Mutations of this gene are associated with Seckel syndrome. (utsouthwestern.edu)
  • 3] Among these effects were the upregulation of two nuclear proteins encoding a Y'-helicase (a subtelomerically encoded protein whose function is to maintain telomeres) and a suppressor of rpc10 and rpb40 mutations (both rpc10 and rpb40 encode RNA polymerase subunits). (adcreview.com)
  • Mutations in sca ABS1 , which encodes the apparent homolog of human nibrin in Aspergillus nidulans, inhibit growth in the presence of the antitopoisomerase I drug camptothecin. (nebraska.edu)
  • In this article, we will take a closer look at the RAD50 gene and its importance, learn about the various types of RAD50 gene mutations, and explore the key risk factors and symptoms associated with these mutations . (tangut.net)
  • RAD50 gene mutations can lead to a variety of defects that disrupt the normal functioning of the MRN complex, thus affecting DNA repair, recombination, and genome stability. (tangut.net)
  • Changes or abnormalities in this gene can occur as a result of genetic inheritance, exposure to toxins or radiation, or through spontaneous mutations. (tangut.net)
  • 1. Loss of Function Mutations: These mutations result in complete or partial loss of RAD50 protein function, leading to defects in DNA repair and recombination. (tangut.net)
  • 2. Missense Mutations: These mutations change the sequence of the RAD50 protein, altering its structure and function. (tangut.net)
  • 3. Frameshift Mutations: These mutations occur when the addition or deletion of nucleotides in the RAD50 gene shifts the reading frame of the genetic code, leading to an altered protein structure and function. (tangut.net)
  • 4. Nonsense Mutations: These mutations cause premature termination of RAD50 protein synthesis, which can lead to truncated or non-functional proteins. (tangut.net)
  • 5. Splice-Site Mutations: These mutations affect the way in which the RAD50 gene is processed during mRNA production, leading to altered protein synthesis. (tangut.net)
  • RAD50 gene mutations can increase the risk of various cancers and other health issues. (tangut.net)
  • Individuals with a positive family history of cancer or other genetic disorders are at higher risk of carrying RAD50 gene mutations. (tangut.net)
  • Exposure to environmental toxins or radiation may also increase the likelihood of gene mutations. (tangut.net)
  • RAD50 gene mutations can be diagnosed through genetic testing, which involves analyzing DNA samples for abnormalities in the RAD50 gene sequence. (tangut.net)
  • Treatment options for RAD50 gene mutations depend on the specific type of mutation and associated symptoms. (tangut.net)
  • Mistakes in the duplication or distribution of the chromosomes lead to mutations that may be passed forward to every new cell produced from an abnormal cell. (openstax.org)
  • Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. (babraham.ac.uk)
  • Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)
  • There are only a few reports on the expression of Ku70/80 in breast cancers [17-21], but the association of this protein with germline CHEK2 mutations in breast cancer patients is unknown. (termedia.pl)
  • Mutations in the genes that encode these proteins can result in disease. (cshl.edu)
  • These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications or deletions and modify gene functions in ways that deregulate cellular signalling pathways leading to the cancer phenotype. (bmj.com)
  • Mutations can cause two basic things to a gene. (pbworks.com)
  • If mutations can occur at random, how does a cell stop a random mutation from effecting the cell. (pbworks.com)
  • Cells contain DNA repair systems that fix DNA mutations. (pbworks.com)
  • Cancer starts out in one cell, and its lineage daughter cells undergo a series of mutations that causes the cells to grow abnormally. (pbworks.com)
  • During the Cell Cycle at the G1, G2, and M phase there are check point proteins that check the integrity of the DNA sequence making sure there are no mutations being passed on. (pbworks.com)
Apoptosis13
Mitosis7
  • Thus, CHK2's inhibition of the CDC25 phosphatases prevents entry of the cell into mitosis. (wikipedia.org)
  • This gene encodes an E3 ubiquitin-protein ligase required for the maintenance of the antephase checkpoint that regulates cell cycle entry into mitosis and, therefore, may play a key role in cell cycle progression and tumorigenesis. (utsouthwestern.edu)
  • It encodes a protein that prevents separin from promoting sister chromatid separation during mitosis [ 3 ]. (biomedcentral.com)
  • The encoded protein is localized to the centromere throughout the cell cycle and is required for bipolar spindle assembly, chromosome segregation and checkpoint signaling during mitosis. (docslib.org)
  • Mitotic chromosomal instability - the inability to faithfully segregate equal chromosome complements to two daughter cells during mitosis - is a widespread phenomenon in solid tumours that is thought to serve as the fuel for tumorigenic progression. (researchgate.net)
  • The advent of molecularly targeted drug discovery has facilitated the identification of a new generation of anti-mitotic therapies that target proteins with specific functions in mitosis. (researchgate.net)
  • The overexpression of it in cancer may overcome an apoptotic checkpoint and favour aberrant progression of transformed cells through mitosis. (innov-research.com)
Progression7
  • This protein acts to integrate signals from ATM and ATR, two cell cycle proteins involved in DNA damage responses, that also associate with chromatin in meiotic prophase I. Phosphorylation of CDC25A protein phosphatase by this protein is required for cells to delay cell cycle progression in response to double-strand DNA breaks. (caslab.com)
  • In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. (affbiotech.com)
  • 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)
  • Correspondingly, most cancer signaling pathways seem to converge on one or more TFs, termed "master regulators" (MRs) [ 4 ], which direct tumor development, progression, and metastasis through hierarchical control of gene expression patterns. (aging-us.com)
  • A checkpoint is one of several points in the eukaryotic cell cycle at which the progression of a cell to the next stage in the cycle can be halted until conditions are favorable. (openstax.org)
  • According to the PPI networks, five hub genes ( TPX2, KIF2C, CDCA8, BUB1B , and CCNA2 ) were identified as key genes associated with breast cancer progression. (biomedcentral.com)
  • Breast cancer initiation and progression is a process involving multiple molecular alterations, many of which are reflected by changes in gene expression in malignant cells. (biomedcentral.com)
Chromatin5
Inhibitors4
  • 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)
  • The features of the senescence phenotype usually consist of the activation of a chronic DNA damage response, the involvement of various cyclin-dependent kinase inhibitors, increased secretion of proinflammatory and tissue-remodeling factors, induction of antiapoptotic genes, altered metabolic rates, and endoplasmic reticulum stress [ 13 ]. (biomedcentral.com)
  • These inhibitors inhibit NHEJ-catalyzed DSB repair and sensitize in vitro cancer cells to DSB-inducing agents. (termedia.pl)
  • To determine the expression of tissue inhibitors of metalloproteinases (TIMP-2) in oral squamous cell carcinoma (OSCC) and the difference in its expression level between positive and negative HPV-16 (human papilloma virus- 16) OSCC patients. (bvsalud.org)
Regulation8
  • 8 , 9 The protein is a member of a novel family of large proteins, which show sequence homology to the catalytic domain of phosphatidylinositol 3 kinase, 3 and are implicated in cell cycle regulation, signal transduction, and the response to DNA damage. (bmj.com)
  • Regulation of gene expression plays a central role in embryonic development. (biomedcentral.com)
  • Our results show that the Tuberin/CycB1 interaction regulates cell size and this regulation is nutrient dependent. (uwindsor.ca)
  • The p53 protein regulates Brca1 transcription both in vitro and in vivo, and Brca1 participates in p53 accumulation after gamma-irradiation through regulation of its phosphorylation and Mdm2 expression. (nih.gov)
  • Cyclins are a group of proteins that play a key role in the control and regulation of the cell cycle. (iiarjournals.org)
  • Selective up-regulation of expression of a subset of genes, including those involved in S-phase checkpoints and the CYCB1;1 gene at the Gâ‚‚-to-M transition, was observed in Atasf1ab. (nih.gov)
  • A clear response to DNA damage was observed, with down-regulation of the DNA replication machinery, changes in transcriptional regulatory proteins, and up-regulation of the biosynthetic enzymes for beta-carotene, which has UV protective properties, and proteins that detoxify reactive oxygen species. (biomedcentral.com)
  • Placing the final piece in the puzzle, the researchers discovered that T cell progenitors in the thymus from mice deficient in the gene Bcl11b exhibited the same halted development and self-renewal cycle, while further experiments connected up-regulation of the transcription factor encoded by this gene to IL-7 levels. (riken.jp)
Mutation11
  • The association between mutation of the ATM gene and a high incidence of lymphoid malignancy in patients with AT, together with the development of lymphoma in Atm deficient mice, supports the proposal that inactivation of the ATM gene may be of importance in the pathogenesis of sporadic lymphoid malignancy. (bmj.com)
  • 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)
  • Importantly, we are inserting the Tuberin-C698Y mutation into the HEK293 cells genome through the CRISPR-Cas9 system to determine the endogenous significance of this specific change. (uwindsor.ca)
  • This mutation is often accompanied by alterations in transformation-related protein 53 (Trp53, encoding p53), which substantially accelerates mammary tumor formation. (nih.gov)
  • This article describes the selection and characterization of extragenic suppressors of the scaA1 mutation, with the aim of identifying other proteins that interfere with the pathway or complex in which the ScaA would normally be involved. (nebraska.edu)
  • Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
  • A mutation is a small change in the DNA structure that alters a particular gene. (pbworks.com)
  • A point mutation occurs when a single amino acid base pair of the gene gets effected. (pbworks.com)
  • A silent mutation changes the nucleotide sequence of a gene, but does not alter the amino acid sequence. (pbworks.com)
  • This mutation may not effect the function of the gene,as long as the substitute amino acid is has a chemistry similar to the original amino acid. (pbworks.com)
  • Sickle Cell disease is an example of a Missense mutation. (pbworks.com)
Tumor suppressor12
  • CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. (wikipedia.org)
  • The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. (affbiotech.com)
  • The tumor suppressor p53 transactivates the expression of a number of genes to exert its multifaceted features and in the end maintains genome stability. (aprofarm.org)
  • 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)
  • Inactivation of tumor suppressor genes, whose products normally provide negative control of cell proliferation, contributes to malignant transformation in various cell types. (medscape.com)
  • [ 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)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (utsouthwestern.edu)
  • It is a tumor suppressor gene, involved in DNA DSB repair through the process of homologous recombination [16]. (termedia.pl)
  • Oncogenes and Tumor suppressor genes are very important when it comes to this cancer topic. (pbworks.com)
  • Tumor suppressor genes are the opposite. (pbworks.com)
Isoforms3
  • Multiple transcript variants encoding different isoforms have been found for this gene. (idhinhibitor.com)
  • Alternatively spliced transcript variants that encode different protein isoforms have been described. (utsouthwestern.edu)
  • Alternatively spliced transcript variants encoding multiple protein isoforms have been observed for this gene. (docslib.org)
Tumors8
  • 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)
  • In solid tumors, the B7-H3 transmembrane protein is an emerging target that harbours two distinct epitope motifs, IgC and IgV, in its ectodomain. (nature.com)
  • Here, we generate dromedary camel nanobodies targeting B7-H3 and demonstrate that CAR-T cells, based on the nanobodies recognizing the IgC but not IgV domain, had potent antitumour activity against large tumors in female mice. (nature.com)
  • However, the successful application of these emerging cell-based therapies in solid tumors remains limited. (nature.com)
  • Random set analysis was used to identify biological pathways enriched for genes differentially regulated in tumors (compared with 59 samples of normal mucosa). (biomedcentral.com)
  • High avidity T cells (Tet hi ), if present, were only found in progressing PD-1 refractory tumors. (bmj.com)
  • Development of most solid tumors is characterized by an increase in secretion and activation of matrix metalloproteinases (MMPs) produced by either the tumor cells or tumor-associated fibroblasts. (bvsalud.org)
  • Small tumors have a greater percentage of actively dividing cells than do large tumors. (msdmanuals.com)
Regulator3
  • Background: The product of this gene is an essential upstream regulator of checkpoint kinase 1 and triggers a checkpoint arrest of the cell cycle in response to replicative stress or DNA damage. (idhinhibitor.com)
  • Identification of master regulator (MR) genes offers a relatively rapid and efficient way to characterize disease-specific molecular programs. (aging-us.com)
  • Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
Response to DNA damage6
  • The protein consists of 543 amino acids and the following domains: N-terminal SQ/TQ cluster domain (SCD) Central forkhead-associated (FHA) domain C-terminal serine/threonine kinase domain (KD) The SCD domain contains multiple SQ/TQ motifs that serve as sites for phosphorylation in response to DNA damage. (wikipedia.org)
  • It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. (caslab.com)
  • This protein and ATM share similarity with Schizosaccharomyces pombe rad3, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. (utsouthwestern.edu)
  • Differential effects on the expression of the three transcription factor B ( tfb ) genes hint at a mechanism for the modulation of transcriptional patterns in response to DNA damage. (biomedcentral.com)
  • However, unlike eukaryotes and bacteria, there was no induction of DNA repair proteins in response to DNA damage, probably because these are expressed constitutively to deal with increased damage arising due to high growth temperatures. (biomedcentral.com)
  • There are no clear archaeal homologues of either bacterial LexA or of eukaryal proteins involved in the transcriptional response to DNA damage, such as p53. (biomedcentral.com)
Pathways5
  • 4 , 10 There is evidence to suggest that these proteins respond to DNA damage by phosphorylating one or more substrates, including p53, c-Abl, and replication protein A (RPA), to recruit proteins to regions of DNA repair and/or to activate radiation signal transduction pathways. (bmj.com)
  • The scsA TOP1 and the scaA NBS1 gene products could functionally interact in pathways that either monitor or repair DNA double-strand breaks. (nebraska.edu)
  • S transition in the cell cycle, upregulated expression of tumor-promoting microenvironmental factors, and profound dysregulation of metabolic pathways (e.g., increased aerobic glycolysis, downregulation of pathways that metabolize drugs and xenobiotics). (biomedcentral.com)
  • The MRN complex plays a critical role in maintaining the stability of genetic material, as it is involved in crucial DNA repair pathways and cell cycle checkpoints. (tangut.net)
  • In addition to DNA repair proteins, bacteria and eukaryotes have damage response pathways whose function is to detect DNA damage and modulate cellular processes. (biomedcentral.com)
Variants2
  • Beyond initial speculations, screening of LFS and LFL patients has revealed no or very rare individual missense variants in the CHEK2 gene. (wikipedia.org)
  • Several alternatively spliced transcript variants have been found for this gene. (caslab.com)
Genome12
  • The oocyte is loaded with maternal mRNAs and proteins that control the cell maintenance and fate and the formation of the body plan prior to the onset of zygotic genome expression [ 3 , 4 ]. (biomedcentral.com)
  • While two genes encoding ASF1 homologues, AtASF1A and AtASF1B, are found in the Arabidopsis genome, their function has not been studied. (nih.gov)
  • RAD50 is a human gene that plays a pivotal role in DNA repair, recombination and genome stability. (tangut.net)
  • The RAD50 protein, in particular, plays a crucial role in homologous recombination, which is an essential mechanism for genome maintenance and repair. (tangut.net)
  • The RAD50 gene plays a critical role in DNA repair, recombination, and genome stability. (tangut.net)
  • Over the last two decades, studies based on genome-wide gene expression and functional profiling have revealed the great diversity of transcriptional alterations occurring in liver carcinogenesis. (aging-us.com)
  • Furthermore, the prognostic value and differential expression of these genes were validated based on data from The Cancer Genome Atlas (TCGA) and Kaplan-Meier (KM) Plotter. (biomedcentral.com)
  • In the mammalian genome, this group of proteins assembles at tens of thousands of sites all at once, ensuring each chromosome is copied precisely once per cell division. (cshl.edu)
  • T-antigen hijacks other proteins from the infected cell to replicate the virus genome. (cshl.edu)
  • Over the next few decades researchers would use SV40 replication to discover dozens of cellular proteins that are necessary for human cell genome replication. (cshl.edu)
  • The Stillman lab searched for the protein(s) that start cell chromosome duplication, rather than virus genome replication. (cshl.edu)
  • To replicate the genome once and only once per cell division, there are many feedback loops, checks, and balances. (cshl.edu)
Cancers4
  • Thus, most cancers cells develop numerous mechanisms to decrease p53 expression and bypass the cell cycle checkpoint. (aprofarm.org)
  • Raw areca nut (RAN) consumption induces oral, esophageal and gastric cancers, which are significantly associated with the overexpression of pituitary tumor transforming gene 1/securin and chromosomal instability (CIN). (biomedcentral.com)
  • STAT proteins - especially STAT3 and STAT5 - regulate all of these processes and are persistently activated in a surprisingly large number of human cancers. (researchgate.net)
  • Survivin is prominently expressed in transformed cell lines and in all the most common human cancers of lung, colon, pancreas, prostate and breast in vivo. (innov-research.com)
Regulates cell1
  • CHK2 regulates cell division, and has the ability to prevent cells from dividing too rapidly or in an uncontrolled manner. (wikipedia.org)
Mitotic5
  • In fact, it has been proposed that these parameters can be considered screening markers for the identification of mitotic checkpoint defects during the early days of RAN exposure. (biomedcentral.com)
  • Centromere-associated protein-E (CENP-E) is an essential mitotic kinesin that is required for efficient, stable microtubule capture at kinetochores. (rupress.org)
  • 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. (rupress.org)
  • 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. (rupress.org)
  • The G 2 checkpoint bars entry into the mitotic phase if certain conditions are not met. (openstax.org)
Oncogenes5
  • The E6 and E7 genes of high-risk HPV genotypes are known oncogenes. (clinicalpathologyassociates.com)
  • 10 Genes that, when activated, contribute to the carcinogenesis are generally termed proto-oncogenes. (bmj.com)
  • The mutated forms of these genes are referred to as oncogenes. (bmj.com)
  • Oncogenes over stimulate everything, thus creating uncontrolled cell division, causing cancer. (pbworks.com)
  • Than once those proto-onco genes change to oncogenes, cancer starts. (pbworks.com)
Arrest7
  • Stabilization of p53 by CHK2 leads to cell cycle arrest in phase G1. (wikipedia.org)
  • Activation of p21 or p16 therefore causes cell cycle arrest. (medscape.com)
  • The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
  • The Atasf1ab mutant plants exhibit cell number reduction, S-phase delay/arrest, and reduced polyploidy levels. (nih.gov)
  • Bcl11b deficiency induces developmental arrest at the myeloid-T progenitor stage, and the arrested myeloid-T progenitors enter a self-renewal cycle. (riken.jp)
  • Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
  • Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
Chromosomes5
  • The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. (lookformedical.com)
  • 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. (lookformedical.com)
  • However, the most important role of the G 2 checkpoint is to ensure that all of the chromosomes have been replicated and that the replicated DNA is not damaged. (openstax.org)
  • Stretching out the DNA in all 46 chromosomes packed into one human cell would make a string of DNA two meters long. (cshl.edu)
  • Not only are ORC proteins involved in DNA replication, but they also help divide the chromosomes equally into the two new cells. (cshl.edu)
Prognostic5
  • Thus, we established a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and radioresistance in PCa. (biomedcentral.com)
  • In view of this, we developed and validated a cellular senescence-related gene prognostic index (CSGPI) to predict metastasis and tumor radioresistance and explored the related changes in the tumor immune microenvironment (TME) for PCa patients undergoing radical radiotherapy. (biomedcentral.com)
  • identified five genes as prognostic biomarkers for breast cancer, and Qiu et al. (biomedcentral.com)
  • To this end, we used real-time quantitative RT-PCR assays to quantify the mRNA expression of a large panel (n = 47) of genes previously identified as candidate prognostic molecular markers in a series of 100 ERα-positive breast tumor samples from patients with known long-term follow-up. (biomedcentral.com)
  • The recurrence is a serious prognostic influence in patients with oral squamous cell carcinoma (OSCC) 1-3 . (bvsalud.org)
Deletion1
  • Most notably, the deletion of a single DNA nucleotide at position 1100 in exon 10 (1100delC) produces a nonfunctional version of the CHK2 protein, truncated at the kinase domain. (wikipedia.org)
Nuclear4
  • 4 - 7 The ATM gene encodes a nuclear phosphoprotein of approximately 350 kDa (3056 amino acids) and is ubiquitously expressed. (bmj.com)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • 3HA-Bfa1 (red) is generally localized to one spindle pole body (SPB) in wild-type cells in metaphase as determined by spindle morphology (tubulin, green) and nuclear morphology (DAPI, blue). (ucsd.edu)
  • 3HA-Bfa1 (red) is generally localized to the daughter spindle pole body (SPB) in wild-type cells in anaphase as determined by spindle morphology (tubulin, green) and nuclear morphology (DAPI, blue). (ucsd.edu)
Suggest that these proteins1
  • The Mre11-Rad50-Nbs1 protein complex has emerged as a central player in the human cellular DNA damage response, and recent observations suggest that these proteins are at least partially responsible for the linking of DNA damage detection to DNA repair and cell cycle checkpoint functions. (nebraska.edu)
Proliferation2
  • Many factors are involved in causing and permitting the unregulated proliferation of cells that occurs in cancer. (msdmanuals.com)
  • Overview of Cancer Cancer is an unregulated proliferation of cells. (msdmanuals.com)
Transcript1
  • An alternatively spliced transcript variant of this gene has been reported, however, its full length nature is not known. (utsouthwestern.edu)
Centrosome1
Homologous recombination1
  • Furthermore, the Atasf1ab-triggered replication fork stalling constitutively activates the DNA damage checkpoint and repair genes, including ATM, ATR, PARP1 and PARP2 as well as several genes of the homologous recombination (HR) pathway but not genes of the non-homologous end joining (NHEJ) pathway. (nih.gov)
Sequence3
  • Immunogen: Recombinant protein encompassing a sequence within the C-terminus region of human Claspin. (idhinhibitor.com)
  • It can change the base sequence of the gene, or it could add or remove nucleotides from a gene. (pbworks.com)
  • Direct Repair is when enzymes modify the base sequence if the gene, for it to be repaired. (pbworks.com)
Serine threon2
Transcription factor2
  • 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)
  • A research team in Japan has linked a developmental checkpoint in the differentiation of hematopoietic progenitors into specific T cell lineages to the activity of a single gene encoding a transcription factor. (riken.jp)
Phenotypes7
  • Using site-directed mutagenesis we constructed six TSC2 mutants to study the phenotypes in HEK293 and NIH3T3 cells. (uwindsor.ca)
  • Tet lo demonstrated precursor exhausted or progenitor T cell phenotypes marked by higher expression of Tcf-1 and T-bet, and lower expression of the exhaustion markers CD39, PD-1 and Eomes compared with Tet hi , whereas Tet hi cells were terminally exhausted. (bmj.com)
  • Transcription factors (TFs) drive gene expression programs that shape specific phenotypes [ 3 ], and are frequently dysregulated in cancer [ 4 ]. (aging-us.com)
  • Thus, MRs comprise typically a small number of TF-encoding genes (and their products) that control a disproportionate level of gene expression, giving rise to distinct molecular phenotypes associated with a particular disease. (aging-us.com)
  • Since the expression of genes defining discrete phenotypes is highly coordinated, application of reverse engineering algorithms to transcriptome datasets allows interpreting transcriptional networks by defining MRs and their associated regulons and gene circuits. (aging-us.com)
  • It can be applied to reveal highly correlative gene sets and explore potential biomarker genes or therapeutic targets according to the internal connectivity of gene clusters and the associations between gene clusters and phenotypes. (biomedcentral.com)
  • By constructing a gene co-expression network and identifying related gene clusters, the correlation between gene modules and phenotypes can be calculated based on phenotypic information, and the most relevant gene modules can be found. (biomedcentral.com)
Mammalian1
  • When fast-dividing mammalian cells are grown in culture (outside the body under optimal growing conditions), the length of the cycle is about 24 hours. (openstax.org)
Kinase family4
  • Specifically, DNA damage-activated phosphatidylinositol kinase family protein (PIKK) ATM phosphorylates site Thr68 and activates CHK2. (wikipedia.org)
  • The protein encoded by this gene belongs to the Ser/Thr protein kinase family. (caslab.com)
  • Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.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. (utsouthwestern.edu)
BRCA11
  • We have previously reported a mouse model in which Brca1 exon 11 is eliminated in mammary epithelial cells through Cre-mediated excision. (nih.gov)
Viral4
Group of proteins1
Spindle4
  • Attachment of each kinetochore to a spindle fiber is assessed at the M checkpoint. (openstax.org)
  • Constitutive targeting of Tem1 to the spindle pole body (SPB) in metaphase cells (this image) and anaphase cells (CIL#13887). (ucsd.edu)
  • MAD2 is a non-essential gene that encodes a component of the spindle checkpoint. (ucsd.edu)
  • The spindle checkpoint delays the o. (ucsd.edu)
Cancer29
  • More than 90% of oral malignant neoplasms are squamous cell carcinomas (OSCC), which are among the ten most frequent malignancies in humans and this entity is the eighth leading cause of cancer-related death worldwide ( 1 ). (iiarjournals.org)
  • Senescent cells have been identified in the aging prostate, and the senescence-associated secretory phenotype might be linked to prostate cancer (PCa). (biomedcentral.com)
  • The researchers noted that the new compound called calicheamicin worked by destroying the DNA of cancer cells. (adcreview.com)
  • This reaction, known as the Bergman cyclization , results in cleaving the DNA and thus destroying the cancer cell. (adcreview.com)
  • Together, they devised a plan to link calicheamicin to a monoclonal antibody that specifically targeted cancer cells. (adcreview.com)
  • This was the very first drug in its class (antibody-targeted chemotherapy agents) and is used in the treatment of acute myelogenous leukemia (AML), a virulent and often fatal form of cancer in which certain white blood cells become cancerous and rapidly accumulate in the bone marrow, preventing normal marrow from growing and functioning properly. (adcreview.com)
  • When this gene is mutated or altered, it can lead to genomic instability, cancer and various other health issues. (tangut.net)
  • Our HCC signature covered well-established liver cancer hallmarks, and network analyses revealed coordinated interaction between several MRs. One novel MR, SEC14L2 , exerted an anti-proliferative effect in HCC cells and strongly suppressed tumor growth in a mouse model. (aging-us.com)
  • Weighted gene co-expression network analysis (WGCNA) was used to screen for the most potent gene modules associated with the metastatic risk of breast cancer, and a total of 12 modules were identified based on the analysis. (biomedcentral.com)
  • Receiver operating characteristic (ROC) curve analysis revealed that the mRNA expression levels of these five hub genes showed excellent diagnostic value for breast cancer and adjacent tissues. (biomedcentral.com)
  • Five hub genes ( TPX2 , KIF2C , CDCA8 , BUB1B , and CCNA2 ) associated with the risk of distant metastasis were extracted for further research, which might be used as biomarkers to predict distant metastasis of breast cancer. (biomedcentral.com)
  • Our results confirm the value of gene expression signatures in predicting the outcome of breast cancer. (biomedcentral.com)
  • Many clinical studies have attempted to identify correlations between altered expression of individual genes and breast cancer outcome, but often with contradictory results. (biomedcentral.com)
  • Consequently, STAT proteins are emerging - unexpectedly - as ideal targets for cancer therapy. (researchgate.net)
  • DNA repair targeted therapy, which kills cancer cells preventing DNA repair [1-3]. (termedia.pl)
  • CHEK2 is not only a breast cancer susceptibility gene but also a multi-organ cancer susceptibility gene [15]. (termedia.pl)
  • Cancer is a disease caused by uncontrolled cell division. (pbworks.com)
  • They encode for proteins to prevent cancer. (pbworks.com)
  • Gene amplification, Chromosome Translocation, and Retroviral Insertion all create cancer. (pbworks.com)
  • This causes an over expression of proto-onco genes causing cancer. (pbworks.com)
  • These proteins play a master role in diverse physiological processes and diseases such as the homeostatic tissue remodeling and cancer 17 . (bvsalud.org)
  • Cancer cells, particularly those arising from the bone marrow or lymphatic system, may have a short generation time, and there usually are a smaller percentage of cells in G0 (resting phase). (msdmanuals.com)
  • A subpopulation of cells within a cancer has the properties of stem cells. (msdmanuals.com)
  • A cancer may release cells into the circulation at a very early stage of development. (msdmanuals.com)
  • Circulating cancer cells are present in many patients with advanced cancer and even in some with localized disease. (msdmanuals.com)
  • Although most circulating cancer cells die, an occasional cell may penetrate into tissues, generating a metastasis at a distant site. (msdmanuals.com)
  • Experiments suggest that the abilities to invade, migrate, and successfully implant and stimulate new blood vessel growth are all important properties of the cells that cause metastases, which are likely a subpopulation of the primary cancer. (msdmanuals.com)
  • Cancer cells often present neoantigens on their cell surface that can be detected as "non-self" by the immune system, resulting in an attack by the immune system. (msdmanuals.com)
  • Basal cell carcinoma (BCC) is a nonmelanocytic skin cancer (ie, an epithelial tumor) that arises from basal cells (ie, small, round cells found in the lower layer of the epidermis). (medscape.com)
Tumour4
  • The TSC2 gene encodes for the protein Tuberin, a tumour suppressor protein well known for it's ability to regulated cell growth and the cell cycle. (uwindsor.ca)
  • Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)
  • The phenomenon of field cancerization (the existence of histologically abnormal tissue beyond a neoplastic area that predisposes to tumour formation) was described in the 1950s on the basis of analyses of squamous cell carcinomas (SCCs). (researchgate.net)
  • Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
Cellular2
  • Transcripts found in unfertilized oocytes also encoded a large number of proteins implicated in cell adherence, tight junction and focal adhesion, suggesting high complexity in terms of structure and cellular interactions in embryos prior to midblastula transition (MBT). (biomedcentral.com)
  • DNA damage leads to cellular responses that include the increased expression of DNA repair genes, repression of DNA replication and alterations in cellular metabolism. (biomedcentral.com)
Expression11
  • Transcriptomic analyses provide an efficient approach to explore the temporal gene expression profiles in embryos and to search for the developmental regulators. (biomedcentral.com)
  • Early ontogeny is associated with dramatic gene expression changes that underlie and determine the developmental processes. (biomedcentral.com)
  • Furthermore, ribosomal proteins and a variety of metabolic, biosynthetic, and stress response genes were also altered in their expression. (adcreview.com)
  • No increase in expression of DNA repair genes following UV irradiation was observed. (biomedcentral.com)
  • RNA sequencing data have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE221590. (bmj.com)
  • The gene expression profiles of GSE102484 were downloaded from the Gene Expression Omnibus (GEO) database. (biomedcentral.com)
  • Weighted gene co-expression network analysis (WGCNA) is a systematic biological strategy for evaluating gene association patterns among different samples [ 11 ]. (biomedcentral.com)
  • The use of gene expression profiles could result in more accurate and objective prognostication. (biomedcentral.com)
  • These tools include cDNA microarrays, which can be used to explore the expression of thousands of genes at a time, and real-time RT-PCR assays for more accurate and quantitative studies of the expression of a smaller number of selected candidate genes. (biomedcentral.com)
  • We identified a three-gene expression signature ( BRCA2 , DNMT3B and CCNE1 ) associated with poor clinical outcome. (biomedcentral.com)
  • How Reliable Are Gene Expression-Based and Immunohistochemical Biomarkers Assessed on a Core-Needle Biopsy? (lu.se)
Nucleus3
  • This truncated variant, cyclin D1b, does not have the part which is required for export from the nucleus into other cell localizations and therefore has higher transforming activity ( 8 ). (iiarjournals.org)
  • Here we report that both AtASF1A and AtASF1B proteins bind histone H3, and are localized in the cytoplasm and the nucleus. (nih.gov)
  • The ORC complex proteins are kept near each other in liquid compartments in the nucleus and recruit proteins such as CDC6 and other proteins that control when to commit the cell to divide. (cshl.edu)
Control6
  • Microarray analyses detected a suite of master developmental regulators that control differentiation and maintenance of diverse cell lineages. (biomedcentral.com)
  • Maternal to zygotic transition (MZT) is the key event during embryogenesis marked by the switch of control from the maternal and possibly paternal transcripts to the newly synthesized embryonic gene products [ 9 - 11 ]. (biomedcentral.com)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • There are six early (E) genes, two late (L) genes, and one untranslated long control region. (clinicalpathologyassociates.com)
  • These include control of the transcriptional repertoire of the cell, activation of repair enzymes and repression of DNA replication and cell division. (biomedcentral.com)
  • cells must control this process with tremendous precision in time and space. (cshl.edu)
Mechanisms2
Abnormalities2
Multiple freeze-thaw cycles1
Defects4
  • Defects in this gene are a cause of Seckel syndrome 1. (sitoolsbiotech.com)
  • Loss-of-function of either AtASF1A or AtASF1B did not show obvious defects, whereas simultaneous knockdown of both genes in the double mutant Atasf1ab drastically inhibited plant growth and caused abnormal vegetative and reproductive organ development. (nih.gov)
  • In spite of the activation of repair genes, an increased level of DNA damage was detected in Atasf1ab, suggesting that defects in the mutant largely exceed the available capacity of the repair machinery. (nih.gov)
  • The theoretical basis for marrow failure includes primary defects in or damage to the stem cell or the marrow microenvironment. (medscape.com)
Histone2
  • Since the molecular mechanism underlying securin upregulation remains unclear, this study intended to investigate the association of securin upregulation with the Rb-E2F1 circuit and epigenetic histone (H3) modification patterns both globally and in the promoter region of the securin gene. (biomedcentral.com)
  • ChIP-qPCR assays were performed to evaluate the recruitment of different histone modifications in the core promoter region of securin gene as well as its upstream and downstream regions. (biomedcentral.com)
Mre11-Rad51
  • The RAD50 gene codes for a protein that is part of a highly conserved protein complex called Mre11-Rad50-NBS1 (MRN). (tangut.net)
Pathway2
  • However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
  • Ku70/80 is a heterodimer of two polypeptides, Ku70 (encoded by XRCC6) and Ku80 (encoded by XRCC5), that binds to DNA double-strand break (DSB) ends and is necessary for the non-homologous end joining (NHEJ) pathway of DNA repair [6]. (termedia.pl)
Damage9
  • The CHK2 protein plays a critical role in the DNA damage checkpoint. (wikipedia.org)
  • The loss of normal CHK2 protein function leads to unregulated cell division, accumulated damage to DNA and in many cases, tumor development. (wikipedia.org)
  • Numerous genes transcribed in oocytes are involved in multiple aspects of cell maintenance and protection, including metabolism, signal perception and transduction, RNA processing, cell cycle, defense against pathogens and DNA damage. (biomedcentral.com)
  • Many environmental factors contribute to the overall load of DNA damage suffered by a cell. (biomedcentral.com)
  • Under normal growth conditions, where levels of DNA damage are low, transcription of repair genes is repressed. (biomedcentral.com)
  • When DNA damage occurs, a damage signal corresponding to the strand exchange protein RecA bound to single-stranded DNA causes the LexA repressor to be degraded, resulting in the induction of transcription of a large number of repair proteins. (biomedcentral.com)
  • Higher DNA damage, p53 overexpression, greater delay in cell kinetics and lower GSH levels in peripheral blood lymphocytes have been demonstrated in heavy RAN chewers than in non-chewers [ 8 ]. (biomedcentral.com)
  • In addition to adequate reserves and cell size, there is a check for genomic DNA damage at the G 1 checkpoint. (openstax.org)
  • The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. (academicinfluence.com)
CHEK22
  • The CHEK2 gene is located on the long (q) arm of chromosome 22 at position 12.1. (wikipedia.org)
  • The evidence from these studies has suggests that CHEK2 is not a predisposition gene to Li-Fraumeni syndrome. (wikipedia.org)
Chromosome duplication1
  • Proper chromosome duplication is assessed at the G 2 checkpoint. (openstax.org)
Essential3
  • Essential gene? (utsouthwestern.edu)
  • It is essential that the daughter cells produced be exact duplicates of the parent cell. (openstax.org)
  • The dynamic regions are most likely essential for regulating and coordinating cell division in a multicellular organism. (cshl.edu)
Interphase2
Roles4
  • Human bulk tissue samples comprise multiple cell types with diverse roles in disease etiology. (kaiserpermanente.org)
  • We were also able to pinpoint specific changes within each gene set that seem to play key roles at each transition. (biomedcentral.com)
  • Further insights on the roles of CD8 + specificities and TCR avidity of naturally arising tumor-specific T cells, where both high and low avidity T cells recognizing the same peptide-major histocompatibility complex (pMHC) coexist in the same tumor, are crucial for understanding T cell exhaustion and resistance to PD-1 immunotherapy. (bmj.com)
  • The blast clade genomes contain more secretome and avirulence effector genes, which likely play key roles in the interaction between Pyricularia species and their plant hosts. (nature.com)
Malignancies1
  • Lymphoid malignancies in patients with AT are of both B cell and T cell origin, and include Hodgkin's lymphoma, non-Hodgkin's lymphoma, and several forms of leukaemia. (bmj.com)
Somatic1
  • The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. (lookformedical.com)
Repair5
  • RAD50 encodes for a protein that is responsible for the proper formation of the MRN complex, which is vital for coordinating DNA repair and recombination processes. (tangut.net)
  • When the RAD50 gene is functioning properly, the MRN complex helps to detect and repair double-strand DNA breaks, which can occur naturally during cell replication or due to external factors such as radiation or exposure to certain chemicals. (tangut.net)
  • Base excision repair proteins, for example, are common to all three domains of life, whilst double-strand break repair appears to be at least partially conserved between eukarya and archaea. (biomedcentral.com)
  • In general, the aim is to ensure that DNA repair proteins are activated and that DNA replication is delayed until repair can be completed. (biomedcentral.com)
  • The DNA repair system contains many proteins that aid in the repair mechanism. (pbworks.com)
Exons1
  • 3 , 4 The ATM gene is located at 11q22-23, spans 184 kb of genomic DNA, and has 66 exons. (bmj.com)
Locus1
  • This locus, however, also encodes a protein from an alternative reading frame, designated p19ARF. (medscape.com)
CycB11
  • We have established that Tuberin binds and regulates the G2/M cyclin, Cyclin B1 (CycB1) creating a new G2/M checkpoint. (uwindsor.ca)