AnatomyOrganismsDiseasesChemicals and DrugsAnalytical, Diagnostic and Therapeutic Techniques and EquipmentPhenomena and ProcessesInformation ScienceHealth Care
Cell Cycle ProteinsCheckpoint Kinase 2DNA DamageProtein-Serine-Threonine KinasesGenes, cdcAtaxia Telangiectasia Mutated ProteinsSaccharomyces cerevisiae ProteinsDNA RepairMad2 ProteinsNuclear ProteinsMitosisDNA-Binding ProteinsM Phase Cell Cycle CheckpointsKinetochoresProtein KinasesSpindle ApparatusCell CycleSchizosaccharomyces pombe ProteinsG2 PhaseSchizosaccharomycesSaccharomyces cerevisiaeCell Cycle CheckpointsCdc20 ProteinsDNA ReplicationS PhaseRad52 DNA Repair and Recombination ProteinNocodazoleHydroxyureaFungal ProteinsDNA Breaks, Double-StrandedPhosphorylationChromosome SegregationDNA, FungalMutationIntracellular Signaling Peptides and ProteinsMethyl MethanesulfonateRad51 RecombinaseMetaphaseGenomic InstabilityRecombination, GeneticG2 Phase Cell Cycle CheckpointsCalcium-Binding ProteinsUltraviolet RaysHeLa CellsDNA Repair EnzymesAnaphasePrometaphaseProtein BindingMeiosisUbiquitin-Protein Ligase ComplexesAnaphase-Promoting Complex-CyclosomeS Phase Cell Cycle CheckpointsCDC2 Protein KinaseCyclin BChromosomal Proteins, Non-HistoneTumor Suppressor ProteinsRadiation, IonizingDNA HelicasesRecombinational DNA RepairMolecular Sequence DataRepressor ProteinsGamma RaysG1 Phasecdc25 PhosphatasesSignal TransductionChromosomal InstabilityReplication Protein ATumor Suppressor Protein p53Aurora KinasesAmino Acid SequenceSecurinHistonesCyclin B1ExodeoxyribonucleasesMicrotubulesEndonucleasesSaccharomycetalesCarrier ProteinsGene Expression Regulation, FungalDNAModels, BiologicalRNA, Small InterferingXenopus ProteinsExonucleasesEndodeoxyribonucleasesGenes, FungalChromosomesChromatinBRCA1 ProteinTelomereAneuploidyTwo-Hybrid System TechniquesCell Line, TumorCell NucleusCell LineSequence Homology, Amino AcidPhosphoproteinsTelomere-Binding ProteinsProtein Structure, TertiaryApoptosis
KINASERad1SchizosaccharomycesCHK1PhosphorylateSubunitGenesPhosphorylationChromatinEukaryoticYeastComplexesHelicaseAtaxiaFamily of proteinsSignaling pathwayDownstreamTumorSaccharomycesGenomicRecruitmentCellularInteractions53BP1Exonuclease activityPolymeraseSensorRegulationRepairAlternativelyApoptoticControlStalled replication forksMechanismSubstratesComplexActivation
KINASE11
  • Whether DNA-dependent protein kinase (DNA-PK) plays any role in this response is unclear. (figshare.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)
  • This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (utsouthwestern.edu)
  • 2. Shen J P,Srivas R,Gross A,et al.Chemogenetic profiling identifies RAD17 as synthetically lethal with checkpoint kinase inhibition[J].Oncotarget,2015,6(34):35755-35769. (nefu.edu.cn)
  • In response to DNA harm phosphatidylinositol (PI)-3 kinase-related kinases ATM (ataxia telangiectasia mutated) and ATR (ATM- and Rad3-related) are primarily activated and eventually phosphorylate several proteins including Rad17 as well as the Chk1 kinase. (biobender.com)
  • The presence of replication stress activates the DNA damage response and downstream checkpoint proteins including ataxia telangiectasia and Rad3 related kinase (ATR), checkpoint kinase 1 (CHK1), and WEE1-like protein kinase (WEE1), which trigger cell cycle arrest while protecting and restoring stalled replication forks. (bmj.com)
  • In addition, we investigated several cell cycle-related proteins and found that co-knockdown of hTopBP1 and hMYH significantly diminished cell cycle arrest due to compromised checkpoint kinase 1 (Chk1) activation. (biomedcentral.com)
  • Rad51-mediated replication of damaged templates relies on monoSUMOylated DDK kinase. (ifom.eu)
  • DDR increased the expression level of pathogenesis-related ( PR ) genes and the total salicylic acid (SA) content and promoted mitogen-activated protein kinase signaling cascades, including the WRKY signaling pathway in Arabidopsis. (ppjonline.org)
  • DDR cascades are activated by ataxia telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) proteins, which are DNA damage sensors and members of the phosphatidylinositol-3 kinase-like family that amplify and transmit signals to downstream components ( Meek, 2009 ). (ppjonline.org)
  • The SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. (academicinfluence.com)
Rad112
  • This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. (wikipedia.org)
  • This family consists of the repair proteins Rad1, Rec1 and Rad17. (embl.de)
  • It forms a checkpoint protein complex with RAD1 and HUS1. (avivasysbio.com)
  • The Rad1 protein, evolutionarily conserved from yeast to humans, exists in cells as monomer as well as a component in the 9-1-1 protein complex. (biomedcentral.com)
  • Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
  • The S. cerevisiae checkpoint protein Rad17, the orthologue of human Rad1, forms a homocomplex in response to treatment with DNA damaging agents, and the complex is required for yeast survival after exposure to genotoxic agents [ 12 ]. (biomedcentral.com)
  • Human Rad1 is a component of a heterotrimeric PCNA like complex that also contains the Rad9 and Hus1 proteins. (biossusa.com)
  • This complex is believed to be involved in cellular responses to DNA damage, possibly by associating with Rad17 and several components of the PCNA-loading heteropentamer, replication factor C. Human Rad1 exhibits significant homology to Rad1 from S. pombe, and its expression in yeast rad1 mutants has been shown to partially restore radiation resistance and G2 checkpoint activity. (biossusa.com)
  • The protein products of several rad checkpoint genes of Schizosaccharomyces pombe (rad1 + , rad3 + , rad9 + , rad17 + , rad26 + , and hus1 + ) play crucial roles in sensing changes in DNA structure, and several function in the maintenance of telomeres. (elsevierpure.com)
  • The purified Rad17 and Rad9-Hus1-Rad1 (9-1-1) complexes can form a stable co-complex in the presence of ATP, using Rad17-Rad9 interactions. (reactome.org)
  • From computer modeling studies, the Rad17 subunit of the complex is also proposed to interact with the C-terminus of Rad1, p36 with the C-terminus of Hus1, and p38 with the C-terminus of Rad9. (reactome.org)
  • Moreover, we observed that hMYH was essential for the accumulation of hTopBP1 on damaged DNA, where hTopBP1 interacts with hRad9, a component of the Rad9-Hus1-Rad1 complex. (biomedcentral.com)
Schizosaccharomyces3
CHK17
  • The ATR-Chk1 axis is certainly central towards the DDR and crucial for preserving genome integrity and they're regarded as DNA harm sensor proteins in cells. (biobender.com)
  • SET8 depletion causes DNA damage specifically during replication, which induces a Chk1-mediated S-phase checkpoint. (rupress.org)
  • Small molecule inhibitors designed to target the DNA damage sensors, such as inhibitors of ataxia telangiectasia-mutated (ATM), ATR, CHK1 and WEE1, impair smooth cell cycle modulation and disrupt efficient DNA repair, or a combination of the above, have demonstrated interesting monotherapy and combinatorial activity, including the potential to reverse drug resistance and have entered developmental pipelines. (bmj.com)
  • Upon loading, the 9-1-1 complex can recruit Chk1 onto sites of replication fork uncoupling or DNA damage. (reactome.org)
  • hTopBP1 and hMYH were involved in ATR-mediated Chk1 activation, moreover, both of them were associated with ATR and hRad9 which known as checkpoint-involved proteins. (biomedcentral.com)
  • The accumulation of hTopBP1 on chromatin and its subsequent interaction with hRad9 lead to cell cycle arrest, a process mediated by Chk1 phosphorylation and ataxia telangiectasia and Rad3-related protein (ATR) activation. (biomedcentral.com)
  • Our results suggested that hMYH is necessary for the accumulation of hTopBP1 to DNA damage lesion to induce the association of hTopBP1 with 9-1-1 and that the interaction between hMYH and hTopBP1 is essential for Chk1 activation. (biomedcentral.com)
Phosphorylate1
  • In contrast, DNA-PK cannot phosphorylate other proteins involved in the checkpoint response, including chromatin-associated Rad17. (figshare.com)
Subunit3
  • The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.com)
  • Although initially discovered as a retinoblastoma binding protein it has an affinity for core HISTONES and is a subunit of chromatin assembly factor-1 and polycomb repressive complex 2. (lookformedical.com)
  • It is found as a subunit of protein complexes that are in involved in the enzymatic modification of histones including the Mi2 and Sin3 histone deacetylase complexes and the polycomb repressive complex 2. (lookformedical.com)
Genes2
  • protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (diff.org)
  • this protein prevents efficient repair of DNA damage, leading to the accumulation of mutations in other genes. (diff.org)
Phosphorylation4
Chromatin5
Eukaryotic2
  • Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)
  • Computed structures of core eukaryotic protein complexes. (ifom.eu)
Yeast4
  • During meiosis in yeast and in mammals, RAD17 protein functions as a DNA damage sensor promoting DNA checkpoint control. (wikipedia.org)
  • In yeast, the RAD17 protein facilitates proper assembly of the meiotic crossover recombination complex containing the RAD51 protein, thus promoting efficient repair of meiotic DNA double-strand breaks. (wikipedia.org)
  • Rad17 is a budding yeast checkpoint protein. (embl.de)
  • Research with yeast resulted in the identification from the conserved mammalian "mitochondria-shaping" protein. (tech-strategy.org)
Complexes2
  • The Rad17-RFC and 9-1-1 complexes are structurally similar to the RFC (replication factor C) clamp loader and PCNA sliding clamp, respectively, and similar mechanisms are thought to be used during loading of the 9-1-1 complex and PCNA. (reactome.org)
  • Thus, hTopBP1 constitutes an important part of the ATR signaling pathway and acts as a molecular bridge that associates the independently recruited 9-1-1 and ATR-ATRIP complexes, thereby leading to checkpoint activation [ 4 ]. (biomedcentral.com)
Helicase1
  • 3. Wan L,Han J H,Liu T,et al.Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase with homologous recombination repair[J].Proceedings of the National Academy of Sciences of the United States of America,2013,110(26):10646-10651. (nefu.edu.cn)
Ataxia2
Family of proteins1
  • PARP-1 is the best-characterized member of the diphtheria toxin-like ADP-ribosyl transferases (ARTDs) family of proteins. (nature.com)
Signaling pathway1
  • Results showed that several apoptotic Tiliroside signaling pathway proteins had been modulated following 0.1 μg/mL of atrazine treatment for 6 h. (biobender.com)
Downstream1
Tumor2
  • Li Q J,Wang D R.Rad17 and its significance in tumor[J].Journal of International Oncology,2011,38(5):336-338. (nefu.edu.cn)
  • Early precancerous lesions in affected person tissues aswell as particular oncogene activation in various tumor models have already been associated with DNA double-strand breaks (DSBs) as well as the activation of DNA-damage checkpoints [31]. (biobender.com)
Saccharomyces1
Genomic4
  • Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)
  • Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. (biomedcentral.com)
  • TP53 is a checkpoint molecule that maintains genomic stability, prevents cell mitosis and induces apoptosis following abnormal chromosome segregation or chemical damage to DNA sequences [ 9 , 10 ]. (biomedcentral.com)
  • The cellular response to DNA damage involves an intricate network of enzymes responsible for sensing, signaling, and repairing damaged DNA, as well as the regulation of cell cycle checkpoints that collectively maintain genomic integrity 2 . (nature.com)
Recruitment2
  • Conversely the dynamin-related protein 1 (Drp1/DNM1) is definitely a cytosolic protein recruitment of which to the OMM from the anchored fission 1 protein (Fis1p/FIS1) adaptor initiates and settings the fission and distribution of mitochondria in cells [19]. (tech-strategy.org)
  • This is accompanied by DNA double-strand break (DSB) induction and recruitment of the DNA repair proteins replication protein A, Rad51, and 53BP1 to damaged regions. (rupress.org)
Cellular2
  • and cellular phenotype that is caused by ATM loss clearly places this protein at a top position in the DSB -response cascade. (diff.org)
  • A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. (lookformedical.com)
Interactions1
  • Through its interactions with other proteins via its BRCT domains, hTopBP1 performs diverse functions [ 1 ]. (biomedcentral.com)
53BP11
  • However, by phosphorylating H2AX, DNA-PK can contribute to the presence of the damage response proteins MDC1 and 53BP1 at the site of the DSB. (figshare.com)
Exonuclease activity1
  • This protein is found to possess 3' to 5' exonuclease activity, which may contribute to its role in sensing and repairing DNA damage. (avivasysbio.com)
Polymerase1
  • Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant and ubiquitous nuclear protein that uses NAD + to synthesize a multibranched polyanion composed of ADP-ribose moieties, giving rise to poly(ADP-ribose) (PAR), onto itself or a variety of target proteins. (nature.com)
Sensor2
  • Animals are known to activate DNA damage responses (DDRs) and DNA damage sensor immune signals in response to stress, and the process is well studied in animal systems. (ppjonline.org)
  • PARP-1 acts as a highly sensitive sensor for DNA damage and rapidly produces PAR at newly generated DNA DSBs. (nature.com)
Regulation1
  • 2.2 Regulation of Apoptosis-Related Protein Expression We then performed apoptosis protein array analysis. (biobender.com)
Repair8
Alternatively2
Apoptotic3
  • The anti-apoptotic Bcl-2 relative Bcl-xL as well as the antagonist BH3 just proteins Bak/Bax had been proven to regulate mitochondrial form in healthful cells aswell such as cells going through apoptosis [13] [14]. (tech-strategy.org)
  • Pro-apoptotic protein including phospho-Rad17 (Ser635) and TNFR1 elevated while Poor p21 and p27 had been Tiliroside inhibited (Body 2 best). (biobender.com)
  • Analysis of expression profile on proteins involved in the apoptotic machinery revealed that, in addition, CD34+ cells from CP-CML were characterized by a significant lower expression of catalase and higher expression of HSP27 and FADD. (oncotarget.com)
Control2
Stalled replication forks2
  • This proceeds to phosphorylating a number of protein that regulate the DNA-damage response (DDR) including cell routine arrest stabilization of stalled replication forks and DNA fix [32]. (biobender.com)
  • During ATR signaling in response to DNA damage, Rad17 forms a complex with 9-1-1 and loads onto stalled replication forks [ 4 - 9 ]. (biomedcentral.com)
Mechanism1
  • Several PAR-binding modules orchestrate the relocation of DDR-associated factors in addition to the accumulation of intrinsically disordered proteins through an intracellular liquid demixing mechanism 11 , 12 . (nature.com)
Substrates1
  • However, the presence of the 9-1-1 complex also alters the ability of Rad17 to become phosphorylated, perhaps suggesting that 9-1-1 may regulate the recruiment of additional ATR substrates. (reactome.org)
Complex3
  • This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. (wikipedia.org)
  • This complex is recruited by checkpoint protein RAD17 to the sites of DNA damage, which is thought to be important for triggering the checkpoint-signaling cascade. (avivasysbio.com)
  • The 9-1-1 complex is a heterotrimeric ring-shaped structure that is loaded onto DNA by the Rad17-RFC complex. (reactome.org)
Activation1
  • Therefore, we suggest that the interaction between hMYH and hTopBP1 is crucial for activation of the ATR-mediated cell cycle checkpoint. (biomedcentral.com)