Response to dna damage checkpoint kinase. Medical search. Frequent questions

ATR-Chk1-mediated protein degradation of Cdc25A protein phosphatase is also a mechanism conferring intra-S-phase checkpoint activation. (kegg.jp)
Checkpoint kinase 1 (Chk1, CHEK1) is a Ser/Thr protein kinase that plays a key role in mediating the cellular response to DNA-damage. (rcsb.org)
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)
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)
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). (salesandmarketingnetwork.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 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)
Hence the ATR-Chk1 axis may be used to check environmental substances that could induce DNA harm. (biobender.com)
In in-vivo and in-vitro experiments, RSK phosphorylated checkpoint kinase 1 (Chk1) at Ser280, an inhibitory site. (cancertherapyadvisor.com)
RSK was found to be the main protein kinase operating downstream of mitogens and oncogenes of the Ras/MAPK pathway, and, in melanoma, RSK constitutively phosphorylated Chk1. (cancertherapyadvisor.com)
In response to DNA-damaging agents, RSK inhibition increased Chk1 activity. (cancertherapyadvisor.com)
RSK promoted silencing of the G2 DNA damage checkpoint in a Chk1-dependent manner. (cancertherapyadvisor.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)

CHEK2 (Checkpoint kinase 2) is a tumor suppressor gene that encodes the protein CHK2, a serine-threonine kinase. (wikipedia.org)
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)
Rabbit anti ATM antibody recognizes serine-protein kinase ATM, also known as ataxia telangiectasia mutated. (bio-rad-antibodies.com)
ATM is a serine/threonine protein kinase and a member of the PI3K/P14K-kinase family. (bio-rad-antibodies.com)
The kinase domain of Nek1, when expressed from bacteria, has dual serine-threonine and tyrosine kinase activity in vitro. (biomedcentral.com)
Serine/threonine-protein kinase 36: Involved in signaling pathways. (github.io)
Higher expression of serine/threonine-protein kinases in mature female gonads (Dheilly et al. (github.io)
2021). Examination of the C. gigas kinome found several serine/threonine-protein kinases in eggs and embryos, with some gene expression changes in response to abiotic stress (Epelboin et al. (github.io)
2017). Several serine/threonine-protein kinases contained DML in C. virginica (Venkataraman et al. (github.io)
The radiation-induced phosphorylation of p53 protein at serine 15, largely mediated by ATM kinase, was defective in AT, A(-T) and in 2/4 heterozygous carriers, while the G1 cell cycle checkpoint was disrupted in all AT and A(-T) cases, and in 3/10 AT heterozygotes. (nih.gov)
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. (lookformedical.com)
An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (lookformedical.com)
Mammalian aurora-A belongs to a multigenic family of mitotic serine/threonine kinases comprising two other members: aurora-B and aurora-C. In this review we will focus on aurora-A that starts to localize to centrosomes only in S phase as soon as centrioles have been duplicated, the protein is then degraded in early G1. (lookformedical.com)
A family of serine/threonine kinase Aurora constitutes a key regulator in the orchestration of mitotic events. (lookformedical.com)

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)
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)
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)
Recent breakthroughs have uncovered more and more DNA replication licensing machinery proteins (ORC, Cdc6, Cdt1, geminin, etc.) functioning in other cell cycle events, including centrosome replication, mitotic events, transcription and so on. (intechopen.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)
7] "A subset of membrane-associated proteins is ubiquitinated in response to mutations in the endoplasmic reticulum degradation machinery. (tcdb.org)
His early research includes seminal work done in 1989, demonstrating the importance of cell cycle proteins in the functioning of DNA tumor viruses. (newswise.com)
The laboratory of Dr. Hasan studies the interplay between anti-apoptotic proteins and cyclin dependent kinases and how this interplay can serve as a potential therapeutic target in Acute Myeloid Leukemia (AML). (actrec.gov.in)
We are interested in understanding at the molecular level how recombination occurs and what roles are played by the many proteins involved in DNA recombination, repair and replication. (brandeis.edu)
We are interested in determining what are the specific biochemical roles played by the many proteins implicated in DNA recombination, repair and replication. (brandeis.edu)
We have identified the proteins necessary to carry out the initial steps in strand invasion and the beginning of new DNA synthesis, which is significantly different from the normal process of replication. (brandeis.edu)

We demonstrate that lack of FAS1 activity results in the activation of an ATAXIA TELANGIECTASIA MUTATED (ATM)- and SUPPRESSOR OF GAMMA-RESPONSE 1 (SOG1)-mediated G2/M-arrest that renders the ATR and WEE1 checkpoint regulators redundant. (muni.cz)
ATM (ataxia-telangiectasia mutated) gene plays a central role in the DNA-damage response pathway. (nih.gov)

HealthDay News) - The mitogen-activated protein kinase (MAPK) p90 ribosomal S6 kinase (RSK) appears to play a role in the poor response of melanoma cells to DNA-damaging agents, according to research published online Oct. 29 in Oncogene . (cancertherapyadvisor.com)

Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
The pre-replication complex (pre-RC) assembly or the DNA replication licensing is the first step in DNA replication initiation, characterized by the sequential recruitment of ORCs, Cdc6, Cdt1 and MCMs to the DNA replication origins to form the pre-RC at the end of mitosis ( Bell and Dutta 2002 ). (intechopen.com)
Neks, mammalian orthologs of the fungal protein kinase never-in-mitosis A, have been implicated in the pathogenesis of polycystic kidney disease. (biomedcentral.com)
Nek1 is a mammalian ortholog of the fungal kinase NIMA (never in mitosis A in Aspergillus nidulans ), which functions in DNA damage responses, regulates G2-M phase progression, and helps keep chromosome transmission to daughter cells faithful [ 5 ]-[ 10 ]. (biomedcentral.com)
DNA damage checkpoint response to accidental DSBs during mitosis requires the Rad53 effector kinase, whereas the meiosis-specific Mek1 kinase, together with Red1 and Hop1, mediates the recombination checkpoint in response to programmed meiotic DSBs. (unimi.it)
activated by interaction with cyclin E during the early stages of DNA synthesis to permit G1-S transition, and subsequently activated by cyclin A2 (cyclin A1 in germ cells) during the late stages of DNA replication to drive the transition from S phase to mitosis, the G2 phase. (proteopedia.org)
Aurora kinase C is a chromosomal passenger protein that interacts with aurora kinase B in the regulation of MITOSIS. (lookformedical.com)
An aurora kinase that localizes to the CENTROSOME during MITOSIS and is involved in centrosome regulation and formation of the MITOTIC SPINDLE. (lookformedical.com)
An aurora kinase that is a component of the chromosomal passenger protein complex and is involved in the regulation of MITOSIS. (lookformedical.com)
The studies on checkpoint control have identified a mechanism by which entry into mitosis is regulated in response to incomplete DNA replication and DNA damage and the identification of a potential target for therapeutic intervention. (actrec.gov.in)
In addition cells have evolved a damage-sensing checkpoint system whereby the cells delay entry into mitosis until the break has been repaired. (brandeis.edu)

However, in the event of DNA damage SCD phosphorylation causes CHK2 dimerization. (wikipedia.org)
The C-terminal domain of hRad9 contains phosphorylation sites and hyperphosphorylation of hRad9 occurs in response to DNA damage [ 10 ]. (biomedcentral.com)
During S phase, helicase activation requires MCM phosphorylation by Dbf4-dependent kinase (DDK), comprising Cdc7 and Dbf4. (bvsalud.org)
Truncation of the Dbf4 docking domain abrogates DH phosphorylation, yet Cdc7 kinase activity is unaffected. (bvsalud.org)
Late origin firing is blocked in response to DNA damage via Dbf4 phosphorylation by the Rad53 checkpoint kinase. (bvsalud.org)
Our results explain the structural basis and regulation of the selective phosphorylation of DNA-loaded MCM DHs, which supports bidirectional replication. (bvsalud.org)
Rad53 phosphorylation/activation is elicited when unrepaired meiosis-specific DSBs escape the recombination checkpoint. (unimi.it)
In response to DNA damage, double-strand break repair by homologous recombination a reduction of CDK2-mediated BRCA2 phosphorylation. (proteopedia.org)
We characterized the ATM protein expression in immortalized cells from AT and AT-variant patients, and heterozygotes and correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest and p53-Ser 15 phosphorylation. (nih.gov)
However, this limited expression of ATM protein provides no benefit regarding the ATM-dependent responses related to G1 arrest and p53-ser15 phosphorylation. (nih.gov)

The concept has now been extended to embrace synthetic lethal drug sensitivity, such as that observed with PARP inhibitors in combination with DNA-damaging chemotherapy in a variety of BRCA defective tumors 10 . (nature.com)
Therefore, compared to normal p53-proficient cells, p53-defective cells are more reliant on MK2 activity, which drives an alternative cell cycle checkpoint pathway that stabilizes the CKI inhibitors p27 Kip1 and Gadd45α in order to maintain G 1 /S and G 2 /M arrest after certain types of DNA damage 16 , 18 . (nature.com)
In a Phase II study, MD Anderson researchers showed that a regimen of neoadjuvant and adjuvant treatment with checkpoint inhibitors nivolumab, a PD-1 inhibitor, and relatlimab, a LAG-3 inhibitor, was safe and effective in patients with resectable clinical stage III melanoma. (mdanderson.org)
Discovery of a Novel Class of Triazolones as Checkpoint Kinase Inhibitors--Hit to Lead Exploration. (rcsb.org)
Furthermore, RSK inhibitors were found to sensitize melanoma cells to agents which induce DNA damage. (cancertherapyadvisor.com)

CHK2 is involved in DNA repair, cell cycle arrest or apoptosis in response to DNA damage. (wikipedia.org)
However, in established cancer cells, such DNA repair system may prevent further DNA damage in their progeny and decrease in apoptosis resulting in enhancement of tumor growth. (biomedcentral.com)
Thus, in addition to its checkpoint control function, hRad9 may play a role in regulating apoptosis. (biomedcentral.com)
When cells are deficient in NIMA or in certain NIMA-related kinases, they undergo apoptosis because of major errors in chromosome segregation. (biomedcentral.com)
Protein phosphatase that is involved in many processes such as microtubule organization at centrosomes, maturation of spliceosomal snRNPs, apoptosis, DNA repair, tumor necrosis factor (TNF)-alpha signaling, activation of c-Jun N-terminal kinase MAPK8, regulation of histone acetylation, DNA damage checkpoint signaling, NF-kappa-B activation and cell migration. (biossusa.com)
p53 is a transcription factor that participates in cell cycle checkpoint processes and apoptosis. (lu.se)

The ATM gene encodes a large protein that belongs to a family of kinases possessing a highly conserved C-terminal kinase domain related to the phosphatidylinositol 3-kinase domain. (bmj.com)

Specifically, DNA damage-activated phosphatidylinositol kinase family protein (PIKK) ATM phosphorylates site Thr68 and activates CHK2. (wikipedia.org)

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)
The laboratories of Dr. Dalal, Dr. Hasan and Dr. Teni study cell cycle progression and checkpoint control. (actrec.gov.in)
p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. (lu.se)
or =10%) predicted a better response (P = 0.014 and P = 0.046, respectively) to treatment and a longer time to progression in both univariate and multivariate analyses. (lu.se)

It is required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. (caslab.com)
Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
Normally, structural damage of DNA by endogenous and environmental agents is followed by replication checkpoint arrest at the G2/M transition in order to allow for repair before proceeding in the cell cycle. (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)
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)
In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. (lu.se)

Knocking out SOG1 in the fast weel background restores replication stress sensitivity, demonstrating that SOG1 is an important secondary checkpoint regulator in plants that fail to activate the intra-S-phase checkpoint. (muni.cz)

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)
The mitotic kinase monopolar spindle 1 (Mps1) is a key regulator of the Spindle assembly checkpoint, which ensures the correct chromosome segregation. (lu.se)

Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
Prior to Heptares, Ali worked as a post-doctoral scientist in Clare Hall Laboratories (a Cancer Research UK institute) and Kudos Pharmaceuticals where he carried out research on the role of cell cycle checkpoint kinases in DNA damage response pathways. (mass-spec-capital.com)
Both homologous recombination, in which the ends of the broken DNA seek out intact templates with the same sequence, and nonhomologous end-joining pathways are found in Saccharomyces as they are in humans. (brandeis.edu)
Functional analysis of these genes indicated that several promising pathways were identified, including the DNA repair related Fanconi Anemia pathway and HIF-1 signaling pathway. (oncotarget.com)
Several pathways involved in cell cycle and DNA repair were affected upon NV651 treatment. (lu.se)

When DNA undergoes a double-strand break, CHK2 is activated. (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)
The loss of normal CHK2 protein function leads to unregulated cell division, accumulated damage to DNA and in many cases, tumor development. (wikipedia.org)
In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)
The aim of this study was to assess the DNA damage response through the expression of checkpoint kinase 2 (CHK2), H2A histone family member X (H2AX), and P53 among smokers and non-smokers with oral squamous cell carcinoma (OSCC). (knoblauchpublishing.com)

His research in High-Throughput Screening Assays intersects with topics in Gene expression profiling, Biological pathway, Transcriptome, DNA microarray and Gene. (research.com)
Our study additionally shows that the majority of AT heterozygotes express almost halved levels of ATM protein, sufficient in most cases to normally regulate the ATM-dependent DNA damage-response pathway. (nih.gov)
Identification of secretory pathway-related genes based on Random Forest algorithm to predict the prognosis and immunotherapy response of hepatocellular carcinoma. (cdc.gov)

For example, a major regulator of metabolism is phosphoinositol 3 kinase (PI3K). (hindawi.com)
Cdc7 is a key regulator of DNA replication and is involved in the DDR network, making it a compelling emerging target for the potential treatment of a broad range of tumor types. (salesandmarketingnetwork.com)

SRA141 is a potent, selective, orally bioavailable small molecule inhibitor of Cell division cycle 7 kinase (Cdc7). (salesandmarketingnetwork.com)
Consistent with this idea, treatment with sorafenib, a multi-kinase inhibitor, has shown survival benefits for late-stage patients [3] - a rare achievement in HCC treatment. (prolekarniky.cz)

Works in various organisms have revealed that the kinase is involved in centrosome separation, duplication and maturation as well as in bipolar spindle assembly and stability. (lookformedical.com)

The PIDDosome multiprotein complex activates p53 in response to extra centrosomes as seen in polyploid cells. (villungerlab.com)

Defects in the ability of cells to properly respond to and repair DNA damage result in genomic instability and underlie many forms of cancer. (mdanderson.org)
Finding of hyperphosphorylated forms of hRad9 in the nucleus of cancer cells is in keeping with its function in ameliorating DNA instability, whereby it inadvertently assists tumor growth. (biomedcentral.com)
The loss of proper response to DNA damage leads to genomic instability such as gene mutations, incomplete replication and the loss or gain of chromosomes to future generations. (biomedcentral.com)

Cyclin-dependent kinases (CDKs) are key regulatory enzymes, each consisting of a catalytic CDK subunit and an activating cyclin subunit. (kegg.jp)

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)
Because BRCA mutations are observed in fewer than 10% of cancer patients (cBioPortal: 6.7%) 11 , 12 , 13 the identification of additional genes that share synthetic lethal sensitivity relationships with mutated oncogenes or tumor suppressors would greatly enhance the implementation of tumor cell-specific synthetic lethal sensitivity to improve an anticancer therapeutic response. (nature.com)
For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
Failure to repair DNA lesions leads to mutations, which can contribute to ageing and cancer. (unimi.it)
We find that there is a 1000-fold increase in mutation rate and that about half the mutations have a distinctive "signature" suggesting that the DNA polymerase frequently dissociates and re-anneals with its template. (brandeis.edu)

Altogether, these data indicate that Rad53 prevents sister chromatid segregation in the presence of unrepaired programmed meiotic DSBs, thus providing a salvage mechanism ensuring genetic integrity in the gametes even in the absence of the recombination checkpoint. (unimi.it)
Role of the Saccharomyces cerevisiae Rad53 checkpoint kinase in signaling double-strand breaks during the meiotic cell cycle / H. Cartagena-Lirola, I. Guerini, N. Manfrini, G. Lucchini, M.P. Longhese. (unimi.it)

Aurora kinases are found in all organisms in which their function has been conserved throughout evolution, namely the control of chromosome segregation. (lookformedical.com)

Her laboratory takes multidisciplinary approach to identify important players in the DNA damage response and define the roles of these genes in maintaining genomic stability and tumor suppression. (mdanderson.org)
This week, I spent a lot of time playing gene librarian and understanding the functions of each of these genes in the gonad or during embryogenesis, probable responses to low pH stress, and overlaps between other studies. (github.io)
Upregulation of numerous IFN-γ-inducible chemokines, class II MHC molecules and immune checkpoint genes was detected as part of the complex immune response to MIBC. (sciencegate.app)
One technique that is garnering wide attention in this realm is the DNA array, in which a number of different genes from an individual can be processed to look at certain genotypes. (medscape.com)
Integrative analysis of cuproptosis-associated genes for predicting immunotherapy response in single-cell and multi-cohort studies. (cdc.gov)

These findings establish a mechanism for co-targeting DNA damage-induced cell cycle checkpoints in combination with repair of cisplatin-DNA lesions in vivo using RNAi nanocarriers, and motivate further exploration of ASL as a generalized strategy to improve cancer treatment. (nature.com)
12] "Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. (tcdb.org)

Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.com)

3) How does the cell protect genome stability in response to DNA replication stress? (mdanderson.org)

3] "Sequence analysis of a 31 kb DNA fragment from the right arm of Saccharomyces cerevisiae chromosome II. (tcdb.org)

Fibroblast growth factor receptor 3 mutation attenuates response to immune checkpoint blockade in metastatic urothelial carcinoma by driving immunosuppressive microenvironment. (cdc.gov)

We show that loss of the DNA repair protein XPA markedly augments the synthetic lethality between MK2 and p53, enhancing anti-tumor responses alone and in combination with cisplatin chemotherapy. (nature.com)
2) How does chromatin modification at sites of DNA damage regulate DNA repair and transcription? (mdanderson.org)
Elevated levels of replicative stress in gynecological cancers arising from uncontrolled oncogenic activation, loss of key tumor suppressors, and frequent defects in the DNA repair machinery are an intrinsic vulnerability for therapeutic exploitation. (bmj.com)
Crucial role in orchestrating a fine balance between cellular proliferation, cell death, and DNA repair in human embryonic stem cells (hESCs). (proteopedia.org)
Driven by a profound interest in the nuclear events that influence human cell health and disease, I dedicated four years to serving as a European Framework for DNA Repair Postdoctoral Research Fellow. (westminster.ac.uk)
This role was based at a pioneering lab in DNA mismatch repair within the Institute of Molecular Cancer Research at the University of Zurich. (westminster.ac.uk)
The PPP4C-PPP4R2-PPP4R3A PP4 complex specifically dephosphorylates H2AFX phosphorylated on Ser-14 (gamma-H2AFX) generated during DNA replication and required for DNA double strand break repair. (biossusa.com)
In response to DNA damage, catalyzes RPA2 dephosphorylation, an essential step for DNA repair since it allows the efficient RPA2-mediated recruitment of RAD51 to chromatin. (biossusa.com)
The main focus of the lab is to characterize DNA repair and cell cycle control mechanisms to understand how defects in these processes contribute to aging, cancer and other genetic syndromes. (unimi.it)
We use a DNA repair-deficient model of ERCC1-XPF in Caenorhabditis elegans to gain insights on how genotoxic stress drives aging. (knoblauchpublishing.com)

We have been fascinated by the process of yeast mating-type gene switching, in which cells replace about 700 bp of Ya or Y-specific DNA sequences at the MAT locus by recombining with one of two donor loci, called HMLDescription: image3 and HMRa. (brandeis.edu)

Nek1 was identified as the first mammalian NIMA-related kinase. (biomedcentral.com)

Her research is focused on understanding how cells respond to DNA damage and safeguard the integrity of the genome. (mdanderson.org)

We have shown that the invasion of DNA strands into a donor template region requires the action of the chromatin remodeling protein Rad54 that enables the recombination machinery to gain access to "closed" regions of DNA. (brandeis.edu)

His laboratory also contributed to understanding how replication origins are regulated by checkpoint kinases in response to DNA damage. (royalsociety.org)
Loading of the eukaryotic replicative helicase onto replication origins involves two MCM hexamers forming a double hexamer (DH) around duplex DNA. (bvsalud.org)
Replication of DNA is initiated at multiple sites along the genome, known as replication origins, which form bidirectional replication forks. (bmj.com)

In contrast, cancer cells shift their metabolism toward lactate production even in the presence of oxygen [ 4 ], partly through genetic modifications that stabilize the transcription factor Hypoxia Inducible Factor (HIF) involved in the adaptation of the cells to hypoxia, under nonhypoxic conditions as well as generating an adaptive response to the hypoxic microenvironment (Figure 1 ). (hindawi.com)
Furthermore, HIF-1 actively limits the mitochondrial consumption of pyruvate at two levels: (i) through the enzyme PDK (PDH-kinase), which in turn inhibits PDH activity preventing the conversion of pyruvate into acetyl CoA, and thereby limiting mitochondrial metabolism of pyruvate [ 6 ] and (ii) through the direct activation of LDH [ 7 , 8 ]. (hindawi.com)
Although DNA damage is intricately linked to metabolism, the metabolic alterations that occur in response to DNA damage are not well understood. (knoblauchpublishing.com)

Since the time of this discovery, two of the three variants (a deletion in the kinase domain in exon 10 and a missense mutation in the FHA domain in exon 3) have been linked to inherited susceptibility to breast as well as other cancers. (wikipedia.org)

This ATM activation accounts for the telomere erosion and loss of ribosomal DNA that are described for fast plants. (muni.cz)

Kinase activity, which have a strong connection to Oxidative stress. (research.com)

Additionally, cyclin-dependent kinase promotes initiation by phosphorylating Sld2 and Sld3. (royalsociety.org)
In this chapter, we mainly discuss the coordination regulations between DNA replication initiation and other cell cycle events that ensure genomic integrity. (intechopen.com)
DNA replication occurs once and only once per cell cycle mainly regulated by DNA replication initiation factors in eukaryotic cells. (intechopen.com)

His laboratory showed that cyclin-dependent kinases prevent pre-RC assembly in budding yeast by inhibiting ORC, and by regulating Cdc6 proteolysis and Mcm2-7 nuclear localisation. (royalsociety.org)
Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by substrate specificity determinants outside the T loop. (proteopedia.org)
His DNA damage research includes elements of Nuclear export signal, Cell cycle checkpoint, Cyclin-dependent kinase 1, Cyclin B1 and Molecular biology. (research.com)

Receptor-interacting protein kinase 1 (RIPK1) is a key component of the tumor necrosis factor (TNF) receptor signaling complex that regulates both pro- and anti-apoptotic signaling. (mdpi.com)

It has been reported that RNF4 negatively regulates TNF-α-induced activation of the nuclear factor-κB (NF-κB) through downregulation of transforming growth factor β-activated kinase 1 (TAK1) activity, indicating the possibility that RNF4-mediated TAK1 suppression results in enhanced sensitivity to cell death. (mdpi.com)

Human Rad 9 ( hRad9 ) was originally identified as a structural homologue of yeast schizosaccharomyces pombe rad 9 , which can partially rescue the sensitivity of rad 9 null yeast to hydroxyurea, radiation damage and the associated checkpoint defects [ 1 ]. (biomedcentral.com)

Some of the most enriched biological processes were lymphocyte activation and proliferation, leukocyte adhesion and migration, antigen processing and presentation and cellular response to IFN-γ. (sciencegate.app)
The role of the protein Mcl-1 in regulating the cellular response to DNA damage has resulted in the determination that drugs targeting Mcl-1 might serve as therapeutics in oral cancer. (actrec.gov.in)

The protein encoded by this gene belongs to the Ser/Thr protein kinase family. (caslab.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)

It also helped to open a very exciting avenue of research involving investigators with expertise in different aspects of growth control and cancer.Giordano's lab also discovered the tumor suppressor gene RB2/p130 and the cell cycle kinases CDK9 and CDK10, two other key players in cell cycle regulation and cell differentiation. (newswise.com)

Presumably the C-terminal domain is essential for transport of the 9-1-1 complex from the cytoplasm into the nucleus, for activation of the G2 checkpoint signalling cascade [ 12 ]. (biomedcentral.com)
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)

Anatomy16

Organisms5

Diseases6

Chemicals and Drugs123

Analytical, Diagnostic and Therapeutic Techniques and Equipment16

Phenomena and Processes77

Information Science3

Health Care2

CHK113

Serine15

Proteins11

ATAXIA TELANGI2

Mitogen-activa1

Mitosis11

Phosphorylation10

Inhibitors5

Apoptosis6

Highly conserved1

Phosphatidylinositol kinase1

Progression4

Arrest6

Intra-S-phase checkpoint1

Mitotic2

Pathways5

CHK27

Pathway3

Regulator2

Inhibitor2

Spindle1

Activates1

Instability3

CDKs1

Mutations5

Rad532

Chromosome segregation1

Genes5

Vivo2

Control following1

Stability1

Saccharomyces1

Immune checkpoint1

Repair10

Locus1

Mammalian1

Respond to DNA damage1

Recombination1

Replication origins3

Metabolism3

Mutation1

Ribosomal1

Oxidative1

Initiation3

Cyclin3

Tumor necros1

Regulates1

Defects1

Cellular response2

Family2

Regulation1

Activation2