Response checkpoint kinase. Medical search. Frequent questions

We examined the G2-specific checkpoint signaling response in these cells and found activation of the ATM/chk2-mediated pathway, whereas the ATR/chk1-mediated response was unaffected. (nih.gov)
CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. (wikipedia.org)
CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. (wikipedia.org)
Specifically, DNA damage-activated phosphatidylinositol kinase family protein (PIKK) ATM phosphorylates site Thr68 and activates CHK2. (wikipedia.org)
Once activated, CHK2 phosphorylates downstream targets including CDC25 phosphatases, responsible for dephosphorylating and activating the cyclin-dependent kinases (CDKs). (wikipedia.org)
The CHK2 protein plays a critical role in the DNA damage checkpoint. (wikipedia.org)
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)
Treatment of standard cultures with Cr(VI) strongly activated ATM, as indicated by its automodification at Ser1981 and by phosphorylation of checkpoint kinase 2 (CHK2) and chromatin/transcription regulator KRAB-associated protein 1 (KAP1). (nih.gov)
Checkpoint kinases CHK1 and CHK2 are activated in response to DNA damage that results in cell cycle arrest, allowing sufficient time for DNA repair. (rcsb.org)
ATM and ATR substrates include checkpoint kinases CHK1 and CHK2, which phosphorylate proteins that mediate cell-cycle arrest. (sdbonline.org)
The results indicate that this arrest is secondary to the activation of a CHK2-mediated DNA checkpoint in early embryos. (sdbonline.org)
Checkpoint kinase 2 (Chk2) is one of the critical kinases governing the cell cycle checkpoint, DNA damage repair, and cell apoptosis in response to DNA damaging signals. (cdc.gov)
In the present report, we demonstrate that Chk2 kinase is degraded at the protein level in response to cisplatin through ubiquitin - proteasome pathway. (cdc.gov)
Rad53 is an essential kinase that shares 24% and 30% identity with the human CHK1 and CHK2 kinases, respectively. (microbialcell.com)
Rad53 is phosphorylated in response to both replication stress (i.e like CHK1) and DNA damage (i.e. like CHK2) in a Mec1 dependent manner. (microbialcell.com)
ATM/Tel1 promote the activation of the downstream effector kinases Rad53 and Chk1 (vertebrate CHK2 and CHK1, respectively) [74]. (pentynoic-acid-stp-ester.com)
thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. (utsouthwestern.edu)

The CHEK2 protein encoded by the CHEK2 gene is a serine threonine kinase. (wikipedia.org)
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)
serine/threonine kinases that relay DNA damage signals to cell cycle checkpoints. (nih.gov)
The ATM serine/threonine kinase (ATM) pathway plays important roles in pancreatic cancer (PanC) development and progression, but the roles of genetic variants of the genes in this pathway in the etiology of PanC are unknown. (duke.edu)
The researchers discovered that functional defects in HR were associated with PARP inhibitor sensitivity, while functional defects in replication fork protection were associated with checkpoint kinase 1 (CHK1) and serine/threonine protein kinase ATR inhibitor sensitivity. (aacr.org)
Results prove that Nim can be characterized by intrinsic activities associated with serine-kinase, threonine-kinase and tyrosine-kinase. (readabstracts.com)
The budding yeast Mec1 is an essential serine/threonine kinase, responsible for mediating the genotoxic stress dependent induction of Rnr3 [4] . (microbialcell.com)
The earliest response to radiation is the activation of ataxia-telangiectasia mutated (ATM), which involves a conformational change that results in the activation of its kinase domain and phosphorylation of serine 1981 (see Fig. 13.3 ). (oncohemakey.com)

Many cancers show aberrant signalling via the insulin-like growth factor (IGF) axis, activating type 1 IGF receptors (IGF-1Rs) and variant insulin receptors (INSRs) to signal via phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) and mitogen-activated protein kinase kinase-extracellular signal-regulated kinases (MEK-ERK) [ 1 ]. (nature.com)
also called Cdc2) cyclin-dependent protein kinase. (nih.gov)
a protein kinase that inhibits Cdk1. (nih.gov)
CDK - a family of cyclin-dependent protein kinases. (nih.gov)
ataxia telangiectasia mutated) a protein kinase that signals the presence of certain types of DNA damage. (nih.gov)
Genetic variants in the liver kinase B1-AMP-activated protein kinase pathway genes and pancreatic cancer risk. (duke.edu)
Research over the past decade has highlighted major roles for protein ubiquitination in regulating cellular responses to DNA damage. (sdbonline.org)
de Lange seeks to understand how telomeres are protected from the DNA damage response by a protein complex called shelterin, how they are replicated and maintained, and how telomere shortening contributes to tumor suppression and genome instability in cancer. (rockefeller.edu)
Recent advances demonstrate that metformin could exert its glucose-lowering effect by multiple mechanisms, including activation of 5′-AMP-activated protein kinase, decreasing production of cyclic AMP, suppressing mitochondrial complex I of the electron transport chain, targeting glycerophosphate dehydrogenase, and altering the gut microbiome. (frontiersin.org)
The protein encoded by this gene belongs the PI3/PI4-kinase family, and is most closely related to ATM, a protein kinase encoded by the gene mutated in ataxia telangiectasia. (genetex.com)
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. (genetex.com)
This kinase has been shown to phosphorylate checkpoint kinase CHK1, checkpoint proteins RAD17, and RAD9, as well as tumor suppressor protein BRCA1. (genetex.com)
The domain is present in a diverse range of proteins, such as kinases, phosphatases, kinesins, transcription factors, RNA-binding proteins and metabolic enzymes which partake in many different cellular processes - DNA repair, signal transduction, vesicular transport and protein degradation are just a few examples. (embl.de)
Here, we show that the two highly divergent FHA domains of Saccharomyces cerevisiae Rad53p, a protein kinase involved in cell cycle checkpoint control, possess phosphopeptide-binding specificity. (embl.de)
The Rad53 protein kinase of Saccharomyces cerevisiae is required for checkpoints that prevent cell division in cells with damaged or incompletely replicated DNA. (embl.de)
The Rad9 protein was phosphorylated in response to DNA damage, and phosphorylated Rad9 interacted with the COOH-terminal forkhead homology-associated (FHA) domain of Rad53. (embl.de)
The FHA domain: a putative nuclear signalling domain found in protein kinases and transcription factors. (embl.de)
1991). Subsequent cloning and characterization of ScTor1p and ScTor2p revealed a C-terminal region with homology to phosphatidylinositol 3-kinases, although no lipid kinase activity has been attributed to either protein (Kunz et al. (nih.gov)
Glc7p functions in opposition to key spindle assembly checkpoint protein Aurora kinase (Ipl1p). (yeastgenome.org)
Mec1 is an ATM/ATR protein, a family of conserved phosphatidylinositol 3-kinase like kinases (PIKKs) best understood for their roles in mediating the DNA damage response (DDR) [5] . (microbialcell.com)
Cell cycle regulation is largely based on protein phospho-dephosphorylation events, catalyzed by cyclin dependent kinases (Cdks) and phosphatases (PPases), respectively. (encyclopedia.pub)
The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. (nih.gov)
This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. (nih.gov)
The Replication Protein A (RPA) complex binds to the ssDNA tails and recruits the ATR/Mec1 checkpoint kinase. (pentynoic-acid-stp-ester.com)
Checkpoint signaling comprises a protein kinase cascade initiated by the two apical protein kinases, which are called ATM and ATR in mammals or Tel1 and Mec1, respectively, in S. cerevisiae (Fig. 2). (pentynoic-acid-stp-ester.com)
ATM and ATR are members of the phosphoinositide 3-kinase-related protein kinase (PIKK) family. (pentynoic-acid-stp-ester.com)
The consensus motif for phosphorylation by ATM/ATR is hydrophobic-X-hydrophobic-[S/T]-Q. Other members of the PIKK family include the DNA-dependent protein kinase (DNA-PK), the homolog of Caenorhabditis elegans SMG-1 (SMG1) and the mammalian target of rapamycin (mTOR). (pentynoic-acid-stp-ester.com)
Activation of the effector kinases requires mediator proteins, among which are the BRCT-domain-containing protein Rad9 and its metazoan ortholog 53BP1 (Fig. 2). (pentynoic-acid-stp-ester.com)
The protein encoded by this gene belongs to the PI3/PI4-kinase family. (utsouthwestern.edu)
This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. (utsouthwestern.edu)
Protein kinase which plays an important role in the G2/M checkpoint response to DNA damage. (nih.gov)
The encoded protein localizes to the nucleoli, and may function with NEK2A in the S-phase checkpoint. (nih.gov)
The encoded protein appears to play roles in DNA replication and response to genotoxic stress. (nih.gov)
This checkpoint has been reconstituted in vitro in Xenopus egg extracts, and here we use antibodies to Xenopus Bub3 (XBub3) to show that this protein is required for both the activation and the maintenance of a spindle checkpoint arrest in egg extracts. (biologists.com)

This degradation was independent of the Thr68 phosphorylation, ATM kinase, and BRCA1 tumor suppressor. (cdc.gov)
We further show that the deaminase ADAL preferentially catabolizes N 6 -methyl-2'-deoxyadenosine monophosphate (6mdAMP) in vitro and in vivo , and adenylate kinase 1 restricts the phosphorylation rate of 6mdAMP, together contributing to the identified checkpoint. (researchsquare.com)
Here we report that induction of this checkpoint with ICRF-193, a topoisomerase H catalytic inhibitor that does not cause DNA damage, was associated with an ATR-dependent inhibition of polo-like kinase 1 (Plk1) kinase activity and a decrease in cyclin B1 phosphorylation. (ulster.ac.uk)
G(2)/M synchronized normal human fibroblasts, when treated with ICRF-193, showed a decrease in cyclin B1 phosphorylation and Plk1 kinase activity despite high cyclin B1-Cdk1 kinase activity. (ulster.ac.uk)
Taken together, these results suggest that ATR-dependent inhibition of Plk1 kinase activity may be one mechanism to regulate cyclin B1 phosphorylation and sustain nuclear exclusion during the G(2) checkpoint response to topoisomerase 11 inhibition. (ulster.ac.uk)
Phosphorylation and inactivation of the mitotic inhibitor Wee1 by the nim1/cdr1 kinase. (readabstracts.com)
The function of nim1/cdr 1 gene product (Nim1) in enhancing the mitotic process by inhibting the action of mitosis inhibtor Wee1 tyrosine kinase was studied by studying the impact of direct phosphorylation. (readabstracts.com)
Inhibition of the Wee1 kinase also occurred with its phosphorylation by purified Nim1 kinase. (readabstracts.com)
Conversely, PP2A Cdc55 counteracts the Cdk1 phosphorylation of the APC/C subunit Cdc16 [ 11 ][ 10 ] , keeping the spindle checkpoint assembly (SAC) active until the cell is prepared for anaphase. (encyclopedia.pub)
Moreover, Rad9 oligomerization is required to maintain checkpoint signaling through a feedback loop involving Rad53-dependent phosphorylation of the Rad9 BRCT domain [80]. (pentynoic-acid-stp-ester.com)

We investigated the effects of Asc restoration in human lung H460 cells and normal human lung fibroblasts on the activation and functional role of ATM kinase, which controls DNA damage responses involving several hundreds of proteins. (nih.gov)
Any process that stops, prevents, or reduces the frequency, rate or extent of the movement of proteins from the cytoplasm into the nucleus, and that occurs as a response to the mitotic cell cycle spindle assembly checkpoint. (yeastgenome.org)
On the other hand, the pathways that respond to DNA damage are very highly conserved in evolution, and the key genes and proteins that regulate and carry out this cellular response feature prominently in both the basic biological phenomena and disease-predisposing defects. (benzon-foundation.dk)
In collaboration with accessory proteins, these two kinases respond to DNA damage by phosphorylating downstream effectors that coordinate 5z progression with DNA repair. (pentynoic-acid-stp-ester.com)
The PIKK enzymes are large proteins (270-450kDa) that have analogous structures, characterized by N-terminal HEAT repeat domains followed by relatively small kinase domains [70]. (pentynoic-acid-stp-ester.com)

Inhibition of the spindle assembly checkpoint kinase Mps-1 as a novel therapeutic strategy in malignant mesothelioma. (nih.gov)
In vitro, CFI-402257-mediated inhibition of Mps-1 resulted in abrogation of the mitotic checkpoint, premature progression through mitosis, marked aneuploidy and mitotic catastrophe. (nih.gov)
6. Phosphoinositide 3-kinase δ inhibition promotes antitumor responses but antagonizes checkpoint inhibitors. (nih.gov)
An ATR-dependent G(2) checkpoint responds to inhibition of topoisomerase 11 and delays entry into mitosis by sustaining nuclear exclusion of cyclin B1-Cdk1 complexes. (ulster.ac.uk)
Recent studies have shown that the inhibition of focal adhesion kinase (FAK) can sensitize PDAC to checkpoint inhibitors and FAK is thought to play a role in immunosuppression and fibrosis. (phrmafoundation.org)
The objective is to understand the mechanism behind FAK inhibition in both tumor and CSC in order to improve PDACs response to immunotherapy and improve disease progression and metastasis. (phrmafoundation.org)
Even more impressive, was the observation that mice with complete responses fully resisted tumor re-challenge performed almost 2 months after discontinuation of therapy, indicating that downregulation of SK1 in tumors combined with immune checkpoint inhibition induced long-term memory immune responses and a durable cure of the animals. (bxcell.com)
Clinical strategies based on combining SK1 inhibition and immune checkpoint inhibition may improve the response rate in patients affected with melanoma or other malignancies. (bxcell.com)
Among other predictions, the model attributes a new role to Hsl1, a kinase known to play a role in Swe1 degradation: Hsl1 must also be indirectly responsible for potent inhibition of Swe1 activity. (nih.gov)

ATM (ataxia-telangiectasia mutated) is an important cell-cycle checkpoint kinase required for cellular response to DNA damage. (duke.edu)
Upon detection of DNA defects, the kinases ATM (ataxia telangiectasia mutated) and ATR (ATM-Rad3-related) are recruited to sites of damage and activated. (sdbonline.org)

Both kinases are shown to phosphorylate Cdc25 on the same sites. (readabstracts.com)

We're seeking partners to continue the development of a cancer biomarker (HORMAD1) for predicting susceptibility to drugs targeting cell division, including spindle checkpoint and kinetochore error correction inhibitors. (icr.ac.uk)
We're seeking a collaborative partner to accelerate the development of an ERAP1 programme in the Centre for Cancer Drug Discovery, with a particular potential to enhance the effectiveness of checkpoint inhibitors or radiotherapy, in patients who do not currently respond to those treatments. (icr.ac.uk)
Two types of EC, the polymerase epsilon (POLE)-ultra-mutated and the microsatellite instability-hyper-mutated (MSI-H), are characterized by a high mutation rate providing the rationale for a potential activity of checkpoint inhibitors. (oncotarget.com)
We analyzed all available evidence supporting the role of tumor microenvironment (TME) in EC development and the therapeutic implications offered by immune checkpoint inhibitors in this setting. (oncotarget.com)
Immune checkpoint inhibitors are an attractive option in POLE-ultra-mutated and MSI-H ECs. (oncotarget.com)
Future investigations in these subgroups include combinations of checkpoints inhibitors with chemotherapy and small tyrosine kinase inhibitors (TKIs) to enhance a more robust intra-tumoral immune response. (oncotarget.com)
However, despite the use of immune checkpoint inhibitors, there is still high morbidity and mortality among these neoplasms. (mdpi.com)

To ensure faithful transmission of the genome upon cell division, eukaryotic cells have developed checkpoints, regulatory pathways that delay cell-cycle progression until completion of prior events. (sdbonline.org)
We and others have reported that in response to a chronic exposure to environmental stressors, in particular UV radiation and PAHs, an activation of AHR and downstream signaling pathways critically contributes to the development of SCC. (frontiersin.org)
Shelterin represses six distinct DNA damage response pathways. (rockefeller.edu)
These include the two main DNA damage signaling pathways, initiated by the ATM and ATR checkpoint kinases, and the DNA double-strand break (DSB) repair pathways involving homology-directed repair (HDR) and non-homologous end joining (NHEJ). (rockefeller.edu)
Shelterin is compartmentalized such that different subunits repress distinct DNA damage response pathways. (rockefeller.edu)
Since TRF2 is responsible for the repression of the ATM kinase pathway and NHEJ, it is likely that the t-loop structure is critical to prevent these two pathways from acting inappropriately on chromosome ends. (rockefeller.edu)
Comparison of I and II surgery samples disclosed a similar distribution of mutated genes, with an overrepresentation of mutations in mismatch repair, cell cycle, p53 and methylation pathways in I surgery samples, and of mutations in receptor tyrosine kinase and MAPK signaling pathways in II surgery samples. (bvsalud.org)
A major complicating issue in this multidisciplinary field has been the widely spread interests of researchers whose work inevitably deals only with a particular aspect of the DNA damage response, such as very diverse model organisms, different aspects of the pathways or their targets, and different 'distance' between the very basic versus clinical research. (benzon-foundation.dk)
The ATR/Mec1 and ATM/Tel1 checkpoint kinases Generation of DNA DSBs triggers the activation of the DNA damage checkpoint signal transduction pathways, which coordinate the DNA damage response [3]. (pentynoic-acid-stp-ester.com)
Research suggests that sulforaphane's effect on Nrf2 pathways, macrophage activation, and NF-kappa B may support a normal, healthy response to inflammation and promote cardiovascular and eye health. (revolutionhealth.org)

This family of kinases is often described as stress-response transducers. (nih.gov)
This gene encodes a member of the never in mitosis gene A family of kinases. (nih.gov)

In response to DNA damage, activated ATM can directly phosphorylate p53 and mdm2, the ubiquitin ligase that targets p53 for degradation. (oncohemakey.com)

The DNA damage/replication checkpoint plays a crucial role in preserving genomic integrity. (sdbonline.org)
Mutagenesis has shown that Chk1 functions redundantly with Cds1 kinase at the replication checkpoint. (readabstracts.com)

3. Antibodies Against Immune Checkpoint Molecules Restore Functions of Tumor-Infiltrating T Cells in Hepatocellular Carcinomas. (nih.gov)
Here, we summarize the current knowledge about AHR's role in skin carcinogenesis and focus on its impact on defense mechanisms, such as DNA repair, apoptosis and anti-tumor immune responses. (frontiersin.org)
Analysis of DNA Damage Response Gene Alterations and Tumor Mutational Burden Across 17,486 Tubular Gastrointestinal Carcinomas: Implications for Therapy. (cdc.gov)
Building upon these studies, this project hopes to demonstrate the mechanism of FAK and elucidate its effect on tumor immunogenicity and cytotoxic T cells to enhance PDACs response to immunotherapy. (phrmafoundation.org)
Strikingly, SK1 silencing dramatically enhanced the response to treatment with Bio X Cell's anti-CTLA-4 (clone 9H10) and anti-PD-1 (clone RMP1-14) antibodies, leading to tumor rejection in 100% and 67% of mice, respectively, and significantly improved overall survival. (bxcell.com)

Regulation RNAPII transcription of genes important in cellular response to changes in nutrient conditions, such as nitrogen levels (Rohde et al. (nih.gov)
This study concluded that portal venous regulation as a response to increasing mesenteric venous flow after a meal challenge may be impaired in patients with cirrhosis. (biospraysehatalami.com)
We report that RNA editor ADAR2 exerts a tissue- and stress-specific regulation of endothelial responses to interleukin-6 (IL-6), which tightly controls leukocyte trafficking in IL-6-inflamed and ischemic tissues. (bvsalud.org)
The carbon source dependent regulation of Rnr3 is mediated by Mec1, the budding yeast ATM/ATR checkpoint response kinase. (microbialcell.com)
Unexpectedly, this regulation is independent of all currently known components of the Mec1 DNA damage response network, including Rad53, Dun1, and Tel1, implicating a novel Mec1 signalling axis. (microbialcell.com)
Follow-up dose response analysis with several siRNAs confirms that the down-regulation of ATR significantly enhances TOP1 poison activity in MDA-MB-231 breast cancer cells. (nih.gov)
The proposed Swe1 network is merged with a model of cyclin-dependent kinase regulation, converted into a set of differential equations and studied by numerical simulation. (nih.gov)
The kinase domain is located near the C-terminus and is flanked by two regions of sequence similarity called FAT (FRAP, ATM, TRRAP) and FATC (FAT C-terminus) domains, which might interact and participate in the regulation of the kinase activity [71]. (pentynoic-acid-stp-ester.com)

Tight balance between Cdc28-Clbs and PP2A Cdc55 activities is important for the adaptation to the spindle checkpoint [ 10 ] . (encyclopedia.pub)
The spindle checkpoint delays the onset of anaphase if there are any defects in the interactions between spindle microtubules and kinetochores. (biologists.com)
We discuss the mechanism by which our α-XBub3 antibodies interfere with the checkpoint and possible roles for XBub3 in the spindle checkpoint pathway. (biologists.com)

reported that deletion of liver kinase B1 (LKB1), the upstream kinase that phosphorylates and activates AMPK, led to a nearly complete loss of AMPK activity in the liver of adult mice. (frontiersin.org)

Activation of a cell cycle checkpoint response was evidenced by autophosphorylation of ATR, the S-phase checkpoint kinase, and by recruitment of ATR and the ATR activators RPA, 9-1-1, and Rad17 to chromatin. (escholarship.org)

Chk1 kinase phosphorylates Cdc25, an activator of Cdc2. (readabstracts.com)

Distinct roles of the ATR kinase and the Mre11-Rad50-Nbs1 complex in the maintenance of chromosomal stability in Arabidopsis. (igred.fr)
have also been shown to play roles in the checkpoint. (biologists.com)

Mre11-Rad50-Nbs1 in mammals), which recruits the checkpoint kinase Tel1/ATM to DSBs. (nih.gov)

In response to genotoxic stress, Mec1 activates RNR via two downstream kinases Rad53 and Dun1 [11] . (microbialcell.com)
Thus the decision to resect a DSB is fundamental not only to initiate DSB repair by HR, but also to activate the ATR/Mec1-mediated checkpoint response. (pentynoic-acid-stp-ester.com)

Checkpoints block mitosis in the cell cycle in response to unreplicated or damaged DNA, usually achieved by preventing activation of the cell-division kinase Cdc2. (readabstracts.com)
There are three principal places in the cell cycle at which checkpoints induced by DNA damage function: the border between G1 phase and S phase, intra-S phase, and the border between G2 phase and mitosis ( Fig. 13.3 ). (oncohemakey.com)

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)
11. Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor. (nih.gov)
We are studying the two most prominent genetic factors in PD-the gene for alpha-synuclein ( SNCA ) and the gene for leucine-rich repeat kinase 2 ( LRRK2 ). (nih.gov)

Rad53 FHA domain associated with phosphorylated Rad9 in the DNA damage checkpoint. (embl.de)

Checkpoint kinases 1 and 2 (Chk1/2) are critical regulators of the DNA-damage response, controlling cell-cycle checkpoints that may permit recovery from therapy-associated genomic stress. (aacrjournals.org)
Moreover, the results demonstrate an important role for the topoisomerase II-dependent G(2) checkpoint in the preservation of human genomic stability. (ulster.ac.uk)
Such a stage has now been reached by the area of research focusing on the molecular mechanisms that monitor and ensure genomic integrity, prevent genetic diseases, and underlie responses to therapeutic modalities such as radiation and chemotherapy. (benzon-foundation.dk)

The unifying theme of these mechanisms, the so-called genome integrity checkpoints activated in response to genotoxic stress encompasses the sensors of DNA damage, the activated signalling cascades, and the downstream targets within the cell-cycle and DNA repair machineries. (benzon-foundation.dk)

Arabidopsis thaliana RNase H2 deficiency counteracts the needs for the WEE1 checkpoint kinase but triggers genome instability. (igred.fr)

Arabidopsis ATM and ATR kinases prevent propagation of genome damage caused by telomere dysfunction. (igred.fr)

A major mechanistic insight came from the identification of the t-loop structure of telomeres in which the single-stranded overhang is inserted in the double-stranded repeat array of the telomere, thereby hiding the telomere end from the DNA damage response. (rockefeller.edu)
Responses to telomere erosion in plants. (igred.fr)
PIK-related kinases are involved in diverse cellular functions including cell growth, cell cycle, DNA damage checkpoints, recombination, and telomere maintenance. (nih.gov)

Essential for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. (nih.gov)

Inducible degradation of checkpoint kinase 2 links to cisplatin-induced resistance in ovarian cancer cells. (cdc.gov)
By heavy stable isotope tracing, we demonstrate that intracellular degradation of RNA m6A cannot induce any misincorporated DNA 6mA, unveiling the existence of a catabolism checkpoint that blocks DNA 6mA misincorporation. (researchsquare.com)
In this work, by taking advantage of unique heavy stable isotope tracing, we examined the misincorporation of DNA i6mA in response to intracellular RNA m6A degradation. (researchsquare.com)

Models for Predicting Response to Immunotherapy and Prognosis in Patients with Gastric Cancer: DNA Damage Response Genes. (cdc.gov)
checkpoint genes ensure that the initiation of late events is delayed until earlier events are complete. (oncohemakey.com)

it is expressed in mouse T lymphocytes of the CD4+ subset with a Th2 profile and human innate effector eosinophils and basophils(13 14 IL-25 has been shown to play a critical role in the initiation and propagation of the Th2 immune response(14-17). (immune-source.com)

Mutations in the ataxia telangiectasia and rad3-related-checkpoint kinase 1 DNA damage response axis in colon cancers. (cdc.gov)

It seems that the best way to promote the field is to gather internationally recognized leaders working on these analogous mechanisms in different eukaryotes (from yeast to men), on different levels of the response (from the DNA lesion recognition to cell cycle arrest and DNA repair), and on emerging medical and pharmacological applications. (benzon-foundation.dk)
Enzyme activated in response to DNA DAMAGE involved in cell cycle arrest. (nih.gov)

Pyrrole-imidazole polyamides targeted to the androgen response element were cytotoxic in multiple cell lines, independent of intact androgen receptor signaling. (escholarship.org)

Overall, this study identifies SK1 as a "checkpoint lipid kinase", able to modulate immune escape mechanisms. (bxcell.com)

A method to predict response or resistance to chemotherapy, utilizing both targeted and conventional agents, would be beneficial in reducing toxicity and improving response rates for patients with STS and also in designing clinical trials for this disease. (medscape.com)

We tested our hypothesis that targeting chromosomal instability in MM would improve response to therapy. (nih.gov)
Mice homozygous for a kinase dead allele exhibit early embryonic lethality associated with genetic instability. (utsouthwestern.edu)

Stern and Murray, 2001 ) can activate a checkpoint-dependent metaphase delay. (biologists.com)

Mathematical model of the morphogenesis checkpoint in budding yeast. (nih.gov)
The morphogenesis checkpoint in budding yeast delays progression through the cell cycle in response to stimuli that prevent bud formation. (nih.gov)

Research suggests that SFN plays a multidimensional role in maintaining normal cellular life cycles, inhibiting tubulin polymerization, activating checkpoint 2 kinase, and inhibiting histone deacetylase activity. (revolutionhealth.org)

Central to the checkpoint mechanism is Swe1 kinase: normally inactive, its activation halts cell cycle progression in G2. (nih.gov)
The model supports the idea that the morphogenesis checkpoint, like other checkpoints, raises the cell size threshold for progression from one phase of the cell cycle to the next. (nih.gov)

We examined the effect of de novo Tax expression upon the cell cycle, because appropriate activation of cell cycle checkpoints is essential to a robust damage-repair response. (nih.gov)
Taken together these data suggest that the TSS describe a unique nuclear site involved in DNA damage recognition, repair response, and cell cycle checkpoint activation. (nih.gov)
Asc restoration in cultured cells dramatically altered their stress responses to Cr(VI) by preventing activation of the oxidant-sensitive ATM network. (nih.gov)
In addition, the lab showed that POT1 prevents ATR kinase activation. (rockefeller.edu)
Reduced proliferation was accompanied by decreased checkpoint activation, induced S-phase accumulation, persistent DNA damage, and increased caspase cleavage and apoptosis. (aacrjournals.org)
Surprisingly, ATR activation was accompanied by only a slight increase in single-stranded DNA, and the ATR targets RPA2 and Chk1, a cell cycle checkpoint kinase, were not phosphorylated. (escholarship.org)
PP2A Cdc55 prevents the untimely activation of the mitotic exit in different ways: by the adaptation to the spindle assembly checkpoint, regulating the cohesin cleavage and by inhibiting Cdc14 release from the nucleolus ( Figure 1 ). (encyclopedia.pub)

Anatomy18

Organisms4

Diseases6

Chemicals and Drugs149

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Phenomena and Processes71

Information Science3

Health Care1

CHK217

Serine8

Protein34

Phosphorylation10

Proteins5

Inhibition9

Ataxia telangi2

Shown to phosphorylate1

Inhibitors7

Pathways10

Family of kinases2

Phosphorylate1

Replication checkpoint2

Tumor5

Regulation8

Spindle checkpoint3

Liver kinase1

RAD171

Phosphorylates1

Roles2

Mre11-Rad51

MEC12

Mitosis2

Gene3

Damage checkpoint1

Genomic3

Genotoxic stress1

WEE11

Genome1

Telomere3

Maintenance of chromosomal stability1

Degradation3

Genes2

Effector1

Mutations1

Cell cycle arrest2

Receptor1

Lipid1

Chemotherapy1

Instability2

20011

Yeast2

Histone1

Progression2

Activation7