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Proliferating Cell Nuclear AntigenCell Cycle ProteinsCell CycleDNA DamageCheckpoint Kinase 2Replication Protein CGenes, cdcMitosisG2 PhaseProtein-Serine-Threonine KinasesCell Cycle CheckpointsM Phase Cell Cycle CheckpointsProtein KinasesSpindle ApparatusAtaxia Telangiectasia Mutated ProteinsDNA RepairS PhaseSaccharomyces cerevisiae ProteinsMad2 ProteinsSchizosaccharomyces pombe ProteinsDNA-Binding ProteinsNuclear ProteinsSchizosaccharomycesHydroxyureaDNA ReplicationG2 Phase Cell Cycle CheckpointsKinetochoresSaccharomyces cerevisiaeFungal ProteinsMutationG1 PhasePhosphorylationGamma RaysTumor Suppressor Protein p53NocodazoleTumor Suppressor ProteinsRad52 DNA Repair and Recombination ProteinCdc20 ProteinsIntracellular Signaling Peptides and ProteinsDNA, FungalDNA Breaks, Double-StrandedChromosomal InstabilityUltraviolet RaysRadiation, Ionizingcdc25 PhosphatasesCyclin BCDC2 Protein KinaseS Phase Cell Cycle CheckpointsRad51 RecombinaseDNA Repair EnzymesGenomic InstabilityMolecular Sequence DataHeLa CellsChromosome SegregationAtaxia TelangiectasiaGenes, FungalCyclin-Dependent Kinase Inhibitor p21MetaphaseCyclin B1Calcium-Binding ProteinsRecombination, GeneticCyclinsSignal TransductionProtein BindingCell DivisionRepressor ProteinsApoptosisMethyl MethanesulfonateRadiation ToleranceAnaphaseCell LineCell Line, TumorG1 Phase Cell Cycle CheckpointsAneuploidyModels, BiologicalUbiquitin-Protein Ligase ComplexesAnaphase-Promoting Complex-CyclosomeAmino Acid SequenceHistonesDNADNA HelicasesMeiosisGene DeletionChromosomal Proteins, Non-HistoneBRCA1 ProteinExonucleasesFibroblastsRNA, Small InterferingAurora KinasesMicrotubulesCell NucleusBase SequenceFlow CytometryCarrier ProteinsReplication Protein AEndonucleasesPrometaphaseCentrosomeRecombinational DNA RepairCDC28 Protein Kinase, S cerevisiae

Maintain genome integrityHeterotrimericHUS1Evolutionarily conservedKinaseRad1InteractsLesionsRolesHRad9ReplicationComplexesCoordinateProstateMechanismsActivationControlRepairFunctionMouseChk1TopBP1LoaderPathwaysMammalianDifferentiationPathwayArrestResponseComplexExpressionHumanNormalIdentifyTargetCoding region

Maintain genome integrity1

• Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)

Heterotrimeric2

• This protein forms a heterotrimeric complex with checkpoint proteins RAD9 and RAD1. (wikipedia.org)
• It is not clear whether Rad1, Rad9 and Hus1 also have distinct functional activities independent of the heterotrimeric form. (biomedcentral.com)

HUS13

• Checkpoint protein HUS1 is a protein that in humans is encoded by the HUS1 gene. (wikipedia.org)
• In somatic cells the RAD9-RAD1-HUS1 (9-1-1) complex responds to DNA damage by promoting DNA repair. (wikipedia.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)

Evolutionarily conserved2

• The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. (wikipedia.org)
• 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)

Kinase2

• The DNA damage induced chromatin binding has been shown to depend on the activation of the checkpoint kinase ATM, and is thought to be an early checkpoint signaling event. (wikipedia.org)
• 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)

Rad13

• 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)
• To determine whether Rad1 functions to maintain genomic stability and prevent tumor development, we generated Mrad1 mutant mice by gene targeting. (biomedcentral.com)

Interacts1

• In response to DNA damage, the trimeric complex interacts with another protein complex consisting of checkpoint protein RAD17 and four small subunits of the replication factor C (RFC), which loads the combined complex onto the chromatin. (wikipedia.org)

Lesions2

• One of the oxidative DNA lesions frequently generated upon exposure of cells to reactive oxygen species (ROS) is 7,8-dihydro-8-oxoguanine (8-oxoG) [ 13 ]. (biomedcentral.com)
• Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. (biomedcentral.com)

Roles1

• Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.com)

HRad93

• 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)
• Besides the existence of 9-1-1 heterotrimer in K562 and 293 human cells, a significant amount of hRad1 also exists in monomeric form, but monomeric hRad9 and hHus1 were not detectable in a study by Karnitz's group [ 10 ] and in our unpublished experiments in 293 human cells. (biomedcentral.com)

Replication1

• Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)

Complexes2

• During mammalian meiosis 9-1-1 complexes promote synapsis of homologous chromosomes, double-strand break repair and cell cycle checkpoint signalling. (wikipedia.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)

Coordinate1

• Activation of ATR phosphorylates a number of downstream proteins that coordinate the cell cycle checkpoint. (biomedcentral.com)

Prostate1

• Knockdown of Rad9 in prostate tumor cells correlates with reduction of tumorigenicity in nude mice [ 16 ]. (biomedcentral.com)

Mechanisms1

• It is likely that increased Rad9 expression is needed for proliferation of tumor cells by mechanisms such as getting beyond (tolerating) oncogene-induced replicative stress and enhancing DNA repair capability. (biomedcentral.com)

Activation2

• Therefore, we suggest that the interaction between hMYH and hTopBP1 is crucial for activation of the ATR-mediated cell cycle checkpoint. (biomedcentral.com)
• It is believed that this complex is important for the function of these three proteins in DNA repair as well as activation of cell cycle checkpoints. (biomedcentral.com)

Control2

• The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)
• Keratinocytes isolated from Mrad1 +/- mice had significantly more spontaneous DNA double strand breaks, proliferated slower and had slightly enhanced spontaneous apoptosis than Mrad1 +/+ control cells. (biomedcentral.com)

Repair1

• DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. (biomedcentral.com)

Function1

• In flies, worms and yeast, the 9-1-1 complex is necessary for meiotic checkpoint function and efficient meiotic recombination. (wikipedia.org)

Mouse1

• The effects of heterozygous deletion of Mrad1 on proliferation and apoptosis of keratinocytes is different from those resulted from Mrad9 heterozygous deletion (from our previous study), suggesting that Mrad1 also functions independent of Mrad9 besides its role in the Mrad9-Mrad1-Mhus1 complex in mouse cells. (biomedcentral.com)

Chk12

• 16. RHINO forms a stoichiometric complex with the 9-1-1 checkpoint clamp and mediates ATR-Chk1 signaling. (nih.gov)
• 18. Topoisomerase II-binding protein 1 promotes the progression of prostate cancer via ATR-CHK1 signaling pathway. (nih.gov)

TopBP13

• 2. STAT-5 Regulates Transcription of the Topoisomerase IIβ-Binding Protein 1 (TopBP1) Gene To Activate the ATR Pathway and Promote Human Papillomavirus Replication. (nih.gov)
• 8. Phosphorylation of the BRCA1 C terminus (BRCT) repeat inhibitor of hTERT (BRIT1) protein coordinates TopBP1 protein recruitment and amplifies ataxia telangiectasia-mutated and Rad3-related (ATR) Signaling. (nih.gov)
• 9. Regulation of E2F1 by BRCT domain-containing protein TopBP1. (nih.gov)

Loader2

• The 9-1-1 complex is recruited to DNA lesion upon damage by the RAD17-replication factor C (RFC) clamp loader complex. (nih.gov)
• 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)

Pathways3

• Hereditary predisposition to breast cancer is largely affected by the mutations in the genes of the DNA repair pathways. (nih.gov)
• The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. (oncotarget.com)
• Combined experiments demonstrated that ZJC can induce G2/M phase cycle arrest and inhibit TAM-induced malignant proliferation by regulating abnormal activation of cell cycle-related proteins such as CDK1, CCNB1, CCNA2 and PI3K-AKT signaling pathways. (bvsalud.org)

Mammalian1

• During mammalian meiosis 9-1-1 complexes promote synapsis of homologous chromosomes, double-strand break repair and cell cycle checkpoint signalling. (wikipedia.org)

Differentiation1

• 1. Topoisomerase IIβ-binding protein 1 activates expression of E2F1 and p73 in HPV-positive cells for genome amplification upon epithelial differentiation. (nih.gov)

Pathway3

• KEGG results showed that the core targets were significantly enriched in the cell cycle, and PI3K-AKT signaling pathway. (bvsalud.org)
• CONCLUSIONS: ZJC may improve TAM-induced SPEM by inhibiting abnormal activation of cell cycle-related proteins (CDK1, CCNB1, CCNA2) and PI3K-AKT signaling pathway. (bvsalud.org)
• Gene set enrichment analysis revealed that the lipid metabolism pathway was suppressed in KDM6B-KO cells. (bvsalud.org)

Arrest1

• The protein encoded by this gene is a component of an evolutionarily conserved, genotoxin-activated checkpoint complex that is involved in the cell cycle arrest in response to DNA damage. (wikipedia.org)

Response1

• 3. DNA damage response is hijacked by human papillomaviruses to complete their life cycle. (nih.gov)

Complex1

• In flies, worms and yeast, the 9-1-1 complex is necessary for meiotic checkpoint function and efficient meiotic recombination. (wikipedia.org)

Expression1

• RESULTS: KDM6B expression levels in HCC cells correlated with the 5-hydroxymethylcytosine levels in the KDM6B gene body region. (bvsalud.org)

Human1

• We investigated the molecular mechanism and role of KDM6B downregulation in NAFLD-related HCC after the KDM6B gene was identified using microarray analysis as commonly downregulated in mouse NAFLD-related HCC and human nonhepatitis B and nonhepatitis C viral-HCC. (bvsalud.org)

Normal1

• Gliomas are the most common primary tumors that arise within the brain and have histologic features similar to normal glial cells (i.e., astrocytes, oligodendrocytes, and ependymal cells). (oncotarget.com)

Identify1

• Microarray and chromatin immunoprecipitation analyses using KDM6B-knockout (KO) cells were used to identify KDM6B target genes. (bvsalud.org)

Target2

• Gene symbols, accession ids and various other target identifiers. (nih.gov)
• Classes for this protein according to by Drug Target Ontology (DTO). (nih.gov)

Coding region1

• We sequenced the coding region of the RHINO gene 466 index cases of Finnish breast cancer families and in 507 population controls. (nih.gov)