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KinaseChk1RAD1PhosphorylationMitosisAtaxiaPathwayGenomic instabilityDownstreamRegulationRegulatory proteinsReplication checkpointApoptoticKinasesChromatinLesionsPathwaysMechanismRad9InteractionsSubunitCellsControlCellularResponseInductionMachineryActivationYeastDepletionSpeciesComplexFoundRoleFamilyTargetFunction

Kinase9

• Checkpoint kinase 1, commonly referred to as Chk1, is a serine/threonine-specific protein kinase that, in humans, is encoded by the CHEK1 gene. (wikipedia.org)
• Two checkpoint kinase subtypes have been identified, Chk1 and Chk2. (wikipedia.org)
• Proteins involved in the ATM-and-Rad3-related kinase (ATR)-dependent S-phase checkpoint response (Chk1 and Rad17) were also phosphorylated but not ataxia telengectasia mutated kinase. (nih.gov)
• 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)
• 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 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 SAD1/RAD53 protein kinase controls multiple checkpoints and DNA damage-induced transcription in yeast. (academicinfluence.com)
• 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)

Chk118

• Chk1 coordinates the DNA damage response (DDR) and cell cycle checkpoint response. (wikipedia.org)
• Activation of Chk1 results in the initiation of cell cycle checkpoints, cell cycle arrest, DNA repair and cell death to prevent damaged cells from progressing through the cell cycle. (wikipedia.org)
• Chk1 is required for the initiation of DNA damage checkpoints and has recently been shown to play a role in the normal (unperturbed) cell cycle. (wikipedia.org)
• In addition to mediating cell cycle checkpoints, Chk1 also contributes to DNA repair processes, gene transcription, egg production, embryo development, cellular responses to HIV infection and somatic cell viability. (wikipedia.org)
• In response to DNA damage, Chk1 is an important signal transducer for G2/M checkpoint activation. (wikipedia.org)
• Chk1 must inactivate in order for the cell to transition from the G2 phase into mitosis, Chk1 expression levels are mediated by regulatory proteins. (wikipedia.org)
• Chk1 has a regulatory role in the spindle checkpoint however the relationship is less clear as compared to checkpoints in other cell cycle stages. (wikipedia.org)
• Studies on Chk1 deficient chicken lymphoma cells have shown increased levels of genomic instability and failure to arrest during the spindle checkpoint phase in mitosis. (wikipedia.org)
• These studies suggest Chk1 depletion can lead to defects in the spindle checkpoint resulting in mitotic abnormalities. (wikipedia.org)
• DNA damage induces the activation of Chk1 which facilitates the initiation of the DNA damage response (DDR) and cell cycle checkpoints. (wikipedia.org)
• However, activation of Chk1 is not solely dependent on ATR, intermediate proteins involved in DNA replication are often necessary. (wikipedia.org)
• Regulatory proteins such as replication protein A, Claspin, Tim/Tipin, Rad 17, TopBP1 may be involved to facilitate Chk1 activation. (wikipedia.org)
• Additional protein interactions are involved to induce maximal phosphorylation of Chk1. (wikipedia.org)
• Chk1 activation can also be ATR-independent through interactions with other protein kinases such as PKB/AKT, MAPKAPK and p90/RSK. (wikipedia.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)
• 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)

RAD14

• 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)
• It forms a checkpoint protein complex with RAD1 and HUS1. (avivasysbio.com)

Phosphorylation3

• Cell cycle progression, phosphorylation, and DNA binding of cell cycle checkpoint proteins were analyzed. (nih.gov)
• Finally we shown that CTMP delayed PKB/Akt phosphorylation following cell death induction suggesting that CTMP regulates apoptosis via inhibition of PKB/Akt. (tech-strategy.org)
• Our results showed that CP-CML CD34+ progenitors were characterized by significant lower phosphorylation of proteins involved in the regulation of growth and cell survival, such as tyrosine kinases of the Src family and members of STAT family, and by a significant higher phosphorylation of p53 (Ser15), compared to normal CD34+ cells from healthy donors. (oncotarget.com)

Mitosis1

• 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)

Ataxia1

• The ataxia telangiectasia and Rad3-related protein (ATR) signaling cascade is an important pathway involved in the checkpoint control mechanism [ 3 ]. (biomedcentral.com)

Pathway4

• These ssDNA structures attract ATR and eventually activates the checkpoint pathway. (wikipedia.org)
• Human DNA topoisomerase II-binding protein 1 (hTopBP1) plays an important role in DNA replication and the DNA damage checkpoint pathway. (biomedcentral.com)
• 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)
• 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)

Genomic instability1

• 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)

Downstream1

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

Regulation2

• 2.2 Regulation of Apoptosis-Related Protein Expression We then performed apoptosis protein array analysis. (biobender.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)

Regulatory proteins1

• Each origin is initiated by a combination of regulatory proteins that prepare the chromatin for replication before synthesis (S)-phase entry. (bmj.com)

Replication checkpoint1

• The activation of replication checkpoint may slow down DNA replication and improve DNA replication fidelity, which increases the maintenance of genomic stability and counteracts carcinogenesis. (nih.gov)

Apoptotic4

• 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)
• 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)
• Pro-apoptotic protein including phospho-Rad17 (Ser635) and TNFR1 elevated while Poor p21 and p27 had been Tiliroside inhibited (Body 2 best). (biobender.com)
• Alternatively the anti-apoptotic proteins clusterin was. (biobender.com)

Kinases2

• Checkpoint kinases (Chks) are protein kinases that are involved in cell cycle control. (wikipedia.org)
• This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS. (lookformedical.com)

Chromatin4

• The 48 kDa subunit, RETINOBLASTOMA-BINDING PROTEIN 4, is also a component of several other protein complexes involved in chromatin remodeling. (lookformedical.com)
• A retinoblastoma-binding protein that is involved in CHROMATIN REMODELING, histone deacetylation, and repression of GENETIC TRANSCRIPTION. (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)
• The repeating structural units of chromatin, each consisting of approximately 200 base pairs of DNA wound around a protein core. (lookformedical.com)

Lesions1

• 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)

Pathways2

• The DNA damage response is a network of signaling pathways that leads to activation of checkpoints, DNA repair and apoptosis to inhibit damaged cells from progressing through the cell cycle. (wikipedia.org)
• In this study, we hypothesized that 5-ASA restrains cell cycle progression by activating checkpoint pathways in colorectal cell lines, which would prevent tumor development and improve genomic stability. (nih.gov)

Mechanism2

• Atrazine was observed to reduce the cell Tiliroside viability at the concentration of 1 1.0 to 10 μg/mL for 48 h in MCF-10A cells (Determine 1) possibly by the mechanism of apoptosis. (biobender.com)
• 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)

Rad91

• RAD9A is highly similar to Schizosaccharomyces pombe rad9, a cell cycle checkpoint protein required for cell cycle arrest and DNA damage repair in response to DNA damage. (avivasysbio.com)

Interactions1

• Through its interactions with other proteins via its BRCT domains, hTopBP1 performs diverse functions [ 1 ]. (biomedcentral.com)

Subunit1

• 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)

Cells8

• Our data demonstrate that 5-ASA causes cells to reversibly accumulate in S phase and activate an ATR-dependent checkpoint. (nih.gov)
• 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)
• Mutant CTMP retained in the mitochondria lost its capacity to sensitize cells to apoptosis. (tech-strategy.org)
• 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)
• 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)
• Strategies that increase replicative stress while lowering cell cycle checkpoint thresholds may allow unrepaired DNA damage to be inappropriately carried forward in replicating cells, leading to mitotic catastrophe and cell death. (bmj.com)
• 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)
• The cells were treated with 0.1 μg/mL of atrazine for 6 h and then the relative levels of 35 apoptosis-related proteins were measured. (biobender.com)

Control2

• Human DNA topoisomerase II-binding protein 1 (TopBP1) and its orthologs play important roles in DNA replication and checkpoint control [ 1 ]. (biomedcentral.com)
• Proteins that control the CELL DIVISION CYCLE. (lookformedical.com)

Cellular1

• A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. (lookformedical.com)

Response2

• 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)
• 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)

Induction1

• 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)

Machinery1

• In the presence of errors or damage during DNA replication, cell cycle checkpoint nodes and repair machinery work in concert to retard cell cycle progression until sufficient repair has been achieved. (bmj.com)

Activation1

• 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)

Yeast1

• Research with yeast resulted in the identification from the conserved mammalian "mitochondria-shaping" protein. (tech-strategy.org)

Depletion1

• Finally, codepletion of Rad51, an important homologous recombination repair protein, abrogates the DNA damage after SET8 depletion. (rupress.org)

Species1

• Proteins obtained from the species SACCHAROMYCES CEREVISIAE. (lookformedical.com)

Complex1

• 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)

Found3

• 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)
• and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell. (lookformedical.com)
• Proteins found in the nucleus of a cell. (lookformedical.com)

Role1

• A histone chaperone protein that plays a role in the deposition of NUCLEOSOMES on newly synthesized DNA. (lookformedical.com)

Family2

• PARP-1 is the best-characterized member of the diphtheria toxin-like ADP-ribosyl transferases (ARTDs) family of proteins. (nature.com)
• The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. (lookformedical.com)

Target1

• 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)

Function1

• The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes. (lookformedical.com)