Genomic stability and cellular stability cell cycle checkpoint gene. Medical search. Frequent questions

Genomic instability , the increased tendency for DNA mutations (e.g., base deletions, additions, or substitutions) and other genetic changes (e.g., chromosome architecture) to occur over time. (foundmyfitness.com)
Telomere attrition , the shortening of the protective caps on the end of DNA that happens as cells divide over time, leaving DNA more vulnerable to mutations. (foundmyfitness.com)
Genomic instability refers to an increased tendency for genetic alterations, such as mutations and chromosome rearrangements, to occur over time during cell division. (foundmyfitness.com)
Defects in processes that modulate cell division, such as mutations in genes that participate in DNA repair, uncorrected errors during replication, or broken, missing, rearranged, or extra chromosomes, are the principal drivers of genomic instability. (foundmyfitness.com)
[ 2 ] Mutations in the NBN ( NBS1) gene located in band 8q21 are responsible for Nijmegen breakage syndrome. (medscape.com)
Thus, somatic mutations, and the consequent genomic instability may be an important driving force for the development of chemoresistance in malignant tumors. (biomedcentral.com)
Our studies are focused on targets of the checkpoint pathways involving the tumor suppressors and the checkpoint kinases CHK1 and CHK2, of which mutations are associated with human cancers. (sinica.edu.tw)
Loss of functional DNA repair genes is a key feature of base pair mutations found in hereditary cancers. (medium.com)
DNA damage predisposes normal cells and transforms into cancer cell mutations with expression of antigenic determinants related to cancer cell life cycle initiation and survival. (medium.com)
Mutations and gene amplifications that confer drug resistance emerge frequently during chemotherapy, but their mechanism and timing are poorly understood. (babraham.ac.uk)
Melanoma in particular exhibits a high incidence of activating BRAF and NRAS mutations and such cells are addicted to the activity of these mutant oncoproteins. (babraham.ac.uk)
Loss of function of oncogenes, tumor suppressor genes and DNA damage processing genes has been implicated in the development of many types of cancer, but for the vast majority of cases, there is no link to specific germ line mutations. (aacrjournals.org)
These alterations can take the form of epigenetic modifications, point mutations, translocations, amplifications or deletions and modify gene functions in ways that deregulate cellular signalling pathways leading to the cancer phenotype. (bmj.com)
This checkpoint control is critical to avoid genomic instability, and mutations in PGE1 ic50 checkpoint genes are often associated with malignancy [19,20]. (ampkpathway.com)
DUSP4 alterations lead to hyperactivation of MAPK signaling in many cancers, including breast cancer, which often harbor mutations in cell cycle checkpoint genes, particularly in TP53. (biomedcentral.com)
This study identifies a novel mechanism for breast tumorigenesis implicating Dusp4 loss and p53 mutations in cellular acquisition of Dbf4 upregulation as a driver of cellular replication and cell cycle checkpoint escape. (biomedcentral.com)
We find that together with loss-of-function mutations in p53 and, to some degree, potentiated by cMyc overexpression, Dusp4 deletion aids in cell cycle checkpoint escape while simultaneously potentiating hallmarks of replicative stress, including multinucleation and Chk1 phosphorylation. (biomedcentral.com)
ALL cancers have lots of additional changes, the so-called 'passenger' mutations, that may contribute to the cancer, but are not the main genes. (cancerquest.org)
Frequent inactivating mutations of the ATM gene have been reported in patients with rare sporadic T cell prolymphocytic leukaemia (T-PLL), B cell chronic lymphocytic leukaemia (B-CLL), and most recently, mantle cell lymphoma (MCL). (bmj.com)
The presence of inactivating mutations, together with the deletion of the normal copy of the ATM gene in some patients with T-PLL, B-CLL, and MCL, establishes somatic inactivation of the ATM gene in the pathogenesis of lymphoid malignancies, and strongly suggests that ATM functions as a tumour suppressor. (bmj.com)
Researchers have identified several hundred mutations in the ATM gene that cause ataxia-telangiectasia. (diff.org)
disorder have mutations in both copies of the ATM gene in each cell. (diff.org)
protein allows mutations to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (diff.org)
this protein prevents efficient repair of DNA damage, leading to the accumulation of mutations in other genes. (diff.org)
However, cancer cells overcome these controls, in particular by acquiring genetic mutations leading to the activation of oncogenes (pten, myc) or loss of tumor suppressors (p53) [ 1 ]. (hindawi.com)
A direct link between DNA DSBs, genomic instability, and cancer is evidenced the fact that many cancer-predisposition syndromes in humans characterized by genomic instability are caused by mutations in DSB-responsive genes ( 16 , 17 ). (amegroups.org)

[3] Cellular checkpoints and DNA damage-response pathways help preserve genomic stability and cell-cycle progression, but these processes decline with aging. (foundmyfitness.com)
Many exogenous and endogenous triggers for senescence have been recognized to act via genomic or epigenomic pathways. (elsevierpure.com)
Numerous E3 ubiquitin ligases, which facilitate the ubiquitination of specific substrates, have been shown to control G1/S. In this chapter, we will discuss components in the ubiquitin proteasome system that are implicated in G1/S control, how these enzymes are interconnected, gaps in our current knowledge, and the potential role of these pathways in the cancer cycle and disease proliferation. (intechopen.com)
Therefore, there are multiple conserved pathways within cells that respond to such errors by recruiting DNA repair processes or initiating apoptosis. (medium.com)
In the last several years, heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways was shown to play a role in genomic instability and carcinogenesis after DNA damage is induced. (aacrjournals.org)
Because the effect of haploinsufficiency for one protein is relatively small, we hypothesize that predisposition to cancer could be a result of the additive effect of heterozygosity for two or more genes, critical for pathways that control DNA damage signaling, repair or apoptosis. (aacrjournals.org)
In the last few years, mounting evidence suggests that heterozygosity leading to haploinsufficiency for proteins involved in DNA repair pathways plays a role in genomic instability and carcinogenesis. (aacrjournals.org)
Here, we review the role of ferroptosis in p53-mediated tumor suppression, with a focus on what cellular factors are critical for p53-dependent ferroptosis during tumor suppression and how p53 modulates both the canonical (GPX4-dependent) and the non-canonical (GPX4-independent) ferroptosis pathways. (nature.com)
Once activated, p53 coordinates multiple downstream pathways, thereby maintaining the homeostasis of the host cell or organism (if the stress is mild, transient, and repairable) or eliminating damaged cells (if the stress is acute, prolonged, and difficult to resist). (nature.com)
The BRCA1-BARD1 heterodimer coordinates a diverse range of cellular pathways such as DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. (helixlabs.ai)
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)
9 The exact number and nature of genetic alterations and deregulated signalling pathways required for tumorigenesis remains an issue of debate, 10 although it is now clear that central nervous system (CNS) carcinogenesis requires multiple disruptions to the normal cellular circuitry. (bmj.com)
Whereas Chk1 and Chk2 have been reported to be involved in unique signaling pathways originally, there is certainly installation proof for a thorough crosstalk between ATR-Chk1 and ATM-Chk2 controlled checkpoint replies [23]. (ampkpathway.com)
Lipids, amino acids, and nucleotides necessary for the biosynthesis of the daughter cells are mostly provided by intermediate metabolites of these pathways. (hindawi.com)
To prevent aberrant cell proliferation, these pathways are tightly regulated. (hindawi.com)
The main role of p53 as a tumor suppressor relies on its transcriptional activity to regulate target genes in a variety of biological pathways (Sullivan et al. (villajoyosacf.info)

The senescence cascade and the cell-cycle checkpoints that dictate the progression and maintenance of senescence are important in all types of gastrointestinal cancers, including pancreatic, liver, gastric, colon, and esophageal cancers. (elsevierpure.com)
During cell growth and proliferation, ubiquitin plays an outsized role in promoting progression through the cell cycle. (intechopen.com)
Progression through the cell cycle is driven by the oscillating activity of Cyclin Dependent Kinases (CDKs). (intechopen.com)
Genomic stability relies around the precise execution of DNA replication, chromosome segregation, DNA repair and genomic monitoring mechanisms, and their integration with cell cycle progression and also other processes. (rockinhibitor.com)
Cancer is a multi-factorial process, however, cancer cell mutation load, tumor initiation and progression through genomic instability has obvious relation to loss of gene function as seen in mutator phenotypes and relation to oncogene initiation and induced DNA replication stress. (medium.com)
This feature of cancer cell mutation and tumor progression has been studied for many decades as a hallmark feature, however, there is much uncertainty in its relation to early process or final transformation process in cancer evolution. (medium.com)
A major conclusion from these data is that, contrary to one of the current views on tumorigenesis, inactivation of one allele of a tumor suppressor gene is enough to contribute to tumor progression. (aacrjournals.org)
Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)
Required for normal cell cycle progression from G2 to mitosis. (helixlabs.ai)
Of the 30,000 or so genes that are currently thought to exist in the human genome , there is a small subset that seems to be particularly important in the prevention, development, and progression of cancer. (cancerquest.org)
Telomere shortening is involved in the progression of CELL AGING. (lookformedical.com)
Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. (hindawi.com)
Once activated by DSBs, ATM/Tel1 and ATR/Mec1 promote DSB repair, delay cell cycle progression or trigger the elimination of genetically unstable cells by inducing cell death. (elifesciences.org)

Understanding the pathogenic mechanisms involved in cellular senescence is important for the development of agents targeted toward the treatment of gastrointestinal tumors. (elsevierpure.com)
Through detailed characterization of fundamental molecular mechanisms of normal and perturbed cells, the theme strives to unravel information that increases the understanding of various diseases such as cancer and neurodegenerative, cardiovascular and inflammatory disorders. (ki.se)
The stem cell and developmental biology program at CMB is engaged in a broad range of basic research aimed at understanding the molecular mechanisms underlying diverse aspects of embryonic development and tissue regeneration. (ki.se)
Extensive emphasis is also made on tissue differentiation and growth during embryogenesis, and deciphering mechanisms underlying the establishment cellular diversity in developing tissues and organs. (ki.se)
Surveillance is a key control integrated in many multi-functions and mechanisms including DNA damage checkpoint, DNA repair machinery and mitotic checkpoint. (medium.com)
I will be elaborating on the stages of DNA surveillance and repair and demonstrate how defects in the regulation of any of these mechanisms often results in genomic instability, which predisposes the cell to malignant transformation. (medium.com)
It is known to halt cancer cell proliferation and the propagation of DNA damage and can also initiate DNA repair mechanisms. (medium.com)
Although the conventional activities of p53 such as cell cycle arrest, senescence, and apoptosis are well accepted as the major checkpoints in stress responses, accumulating evidence implicates the importance of other tumor suppression mechanisms. (nature.com)
To date, various mechanisms have been suggested to explain the powerful tumor-suppressive effect of p53, including the induction of cell cycle arrest, senescence, and apoptosis. (nature.com)
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)
In addition to its role in NHEJ, Ku70/80 is also required for telomere length maintenance [9] and other important cellular mechanisms. (termedia.pl)
These CIN mechanisms and their signatures can be largely found in acute myeloid leukemia (AML), a heterogeneous disease characterized by abnormal proliferation and accumulation of myeloid precursor cells in the bone marrow [ 13 ] . (encyclopedia.pub)
Transmembrane and intracellular signal transduction mechanisms are the focus of our group, especially understanding how extracellular stimuli control cell growth and division, cell morphology, and gene expression at the biochemical level. (berkeley.edu)
We investigated control mechanisms that regulate the activity, localization, and stability of Wee1, especially the bud neck-localized protein kinase Hsl1 and its more distant paralogs (Gin4 and Kcc4), in particular their recruitment to septin filaments, which assemble at the presumptive site of cell division. (berkeley.edu)
Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS. (lookformedical.com)
In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)
Homologous recombination' is one of the main mechanisms used by cells to repair DNA double-strand breaks. (elifesciences.org)
The disorders are characterized by a defect in DNA repair mechanisms or genomic instability, and patients with these disorders show increased predisposition to cancer. (medscape.com)

TP53 is a checkpoint molecule that maintains genomic stability, prevents cell mitosis and induces apoptosis following abnormal chromosome segregation or chemical damage to DNA sequences [ 9 , 10 ]. (biomedcentral.com)

8- 10 In attempts to identify new breast and ovarian cancer susceptibility genes, much research has focused on BRCA1 associated proteins. (bmj.com)

Activated p53 induces programmed cell death (apoptosis) or senescence as a last attempt to avoid possible malignant transformation when the damage is too severe and beyond repair. (medium.com)
Is p53-dependent ferroptosis sufficient for tumor suppression in the absence of cell cycle arrest, senescence, and apoptosis? (nature.com)
The generation of cellular models of drug resistance has been pivotal in unravelling the main effectors of resistance to traditional chemotherapy at the molecular level (i.e. intracellular drug inactivation, detoxifying systems, defects in DNA repair, apoptosis evasion, membrane transporters and cell adhesion). (nature.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)
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)
Upon treatment with Plk1 inhibitors, p53 in tumor cells is activated and induces strong apoptosis, whereas tumor cells with inactive p53 arrest in mitosis with DNA damage. (oncotarget.com)
In addition, compared to the mono-treatment, combination of Polo-like kinase 1 inhibition with anti-mitotic or DNA damaging agents boosts more severe mitotic defects, effectually triggers apoptosis and strongly inhibits proliferation of cancer cells with functional p53. (oncotarget.com)
It is also involved in cell cycle arrest and apoptosis [17]. (termedia.pl)
On the other hand, extreme levels of CIN could lead to decreased cell fitness or apoptosis [ 9 ] . (encyclopedia.pub)
The p53-inducible gene 3 (PIG3) was originally indentified by Polyak et al in the analysis of p53-induced genes related to the onset of apoptosis ( 1 ). (ijbs.com)
In some p53 mutants, induction of cell cycle arrest, but not apoptosis was found to be associated with a lack of induction of PIG3 expression ( 2 ). (ijbs.com)
Additionally, PIG3 mediates cancer cell death through the GPx3 pathway, and knocking down PIG3 or blocking the interaction between PIG3 and GPx3 would abolish the increase in ROS and apoptosis ( 5 ). (ijbs.com)
Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
JNK1 shRNA expressing INS1 cells demonstrated elevated apoptosis and cleaved caspase 9 and 3 in comparison to nonsense shRNA expressing control INS1 cells when subjected to palmitate and high blood sugar associated with elevated CHOP appearance, ROS development and mRNA appearance. (cgp60474.com)
JNK2 shRNA expressing INS1 cells didn't influence palmitate and high blood sugar induced apoptosis or ER tension markers, but increased appearance in comparison to non-sense shRNA expressing INS1 cells mRNA. (cgp60474.com)
Finally, JNK3 shRNA expressing INS1 cells didn't induce apoptosis in comparison to nonsense shRNA expressing INS1 cells when subjected to palmitate and high blood sugar but showed elevated caspase 9 and 3 cleavage connected with elevated and mRNA appearance. (cgp60474.com)
These data claim that JNK1 protects against palmitate and high glucose-induced -cell apoptosis connected with decreased ER and mitochondrial tension. (cgp60474.com)
Long term and extreme ER tension induced -cell apoptosis is certainly connected with c-jun N-terminal kinase (JNK) activation [9], [15]. (cgp60474.com)
In proinflammatory cytokine-induced -cell apoptosis JNK activation is quite transient and rapid [20]. (cgp60474.com)
The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS. (lookformedical.com)
A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.com)

Protein KIAA1958 is a protein that in humans is encoded by the KIAA1958 gene. (wikipedia.org)
The gene has these neighbors on chromosome 9: HSDL2: Hydroxysteroid dehydrogenase-like protein 2 plays a role in nucleotide binding, oxidoreductase activity, and sterol binding. (wikipedia.org)
The key interests lie within the field of genome integrity and variation, cell division, regulation of gene expression, protein turnover and signal transduction. (ki.se)
The small protein ubiquitin plays a vital role in virtually all aspects of cellular life. (intechopen.com)
The Rep proteins and the plasmid-encoded Raf protein also regulate plasmid gene transcription. (bvsalud.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)
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)
E3 ubiquitin-protein ligase that specifically mediates the formation of 'Lys-6'-linked polyubiquitin chains and plays a central role in DNA repair by facilitating cellular responses to DNA damage. (helixlabs.ai)
The BRCA2 R3052W mutated protein exacerbates genome instability, is unable to rescue homology-directed repair, and fails to complement cell survival following exposure to PARP inhibitors and crosslinking drugs. (frontiersin.org)
and individual cells, a larger than 90% decrease in MCM proteins concentrations will not impair DNA replication [11C15], recommending a job for MCM protein beyond DNA replication. (ampkpathway.com)
Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
Genes whose protein products stimulate or enhance the division and viability of cells. (cancerquest.org)
Genes whose protein products can directly or indirectly prevent cell division or lead to cell death. (cancerquest.org)
As an example TP 53 refers to the gene and p53 refers to the protein. (cancerquest.org)
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)
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)
Notably, PIG3 knockdown resulted in a striking depression of cellular DNA-PKcs protein level, and was accompanied by a downregulation of ATM. (ijbs.com)
However, a compensatory feedback of increased mRNA expression of DNA-PKcs was formed in PIG3-depleted cells after a few passages or cell cycles of subculture, which led the recovery of the DNA-PKcs protein level and the consequent recovered efficiency of the DNA damage response. (ijbs.com)
and cellular phenotype that is caused by ATM loss clearly places this protein at a top position in the DSB -response cascade. (diff.org)
Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (diff.org)
Cells that are missing one copy of the ATM gene produce half the normal amount of ATM protein. (diff.org)
This includes gene, protein and metabolic networks, cellular architecture and intracellular dynamics, cell communication and motility, cell division and differentiation, tissue formation and organogenesis, tissue and organ functions, changes in population characteristics as a consequence of interaction of organisms with their physical environment, with individuals of their own species, and with organisms of other species. (nih.gov)
The Wee1 class of protein-tyrosine kinase has an important role in cell cycle control. (berkeley.edu)
We also studied the roles of other classes of protein kinases (Cla4) and additional post-translational modifications (SUMOylation) in septin complex assembly, formation of different septin-based supramolecular ensembles, disassembly of septin-containing structures, and the function of septin organization in the events required for cell division and membrane septation during cytokinesis. (berkeley.edu)
More recently, his group invented tools for cleavage-free large gene insertion via mining microbial recombination protein, and developed single-cell tracking approach for studying cancer biology and cancer immunology. (stanford.edu)
from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin. (lookformedical.com)
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. (lookformedical.com)
D) Cytoplasmic and nuclear ZKSCAN5 protein levels in two types of breast cancer cell lines, ZR75-1 and MDA-MB-231. (bms-911543.com)
DNA nuclease/helicase 2 (DNA2), a multi-functional protein protecting the high fidelity of genomic transmission, plays critical roles in DNA replication and repair processes. (longevityfacts.com)
DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key component of the non-homologous end-joining (NHEJ) pathway, is involved in DNA double-strand break repair, immunocompetence, genomic integrity, and epidermal growth factor receptor signaling. (amegroups.org)
The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is the key component of the non-homologous end-joining (NHEJ) pathway for DNA double-strand break (DSB) repair and is required for cellular resistance to ionizing radiation (IR) ( 1 , 2 ). (amegroups.org)
In this review, we describe the effects of MDM2 on genomic instability, the role of MDM2 in p53 release and binding of DNA repair proteins to inhibit repair, and the regulatory network of MDM2, including its transcriptional modifications, protein stability, and localization. (villajoyosacf.info)

The SOSS complex associates with single-stranded DNA at DNA lesions and influences diverse endpoints in the cellular DNA damage response including cell cycle checkpoint activation, recombinational repair and maintenance of genomic stability. (wikipedia.org)
29 Moreover, a recent study in mice showed that loss of Bard1 results in early embryonic lethality and chromosomal instability, indicating a role of Bard1 in maintenance of genomic integrity. (bmj.com)
Maintenance of genomic stability is crucial for standard development, cell homeostasis and tumor suppression [7]. (rockinhibitor.com)

Approximately 5-10% of all breast and ovarian cancers are thought to arise from a hereditary predisposition to the disease, 1 BRCA1 and BRCA2 being the most important susceptibility genes. (bmj.com)
It was previously found that the inhibition of MUS81 elevated susceptibility to PARP inhibitors by means of HR deficiency at the cellular level [14]. (rockinhibitor.com)
Disease susceptibility is associated with variations affecting the gene represented in this entry. (helixlabs.ai)
CHEK2 is not only a breast cancer susceptibility gene but also a multi-organ cancer susceptibility gene [15]. (termedia.pl)
Carcinogenesis is a multi-step process wherein abrogation of multiple cancer susceptibility genes leads to cancer development. (amegroups.org)

Cellular senescence , the process by which damaged cells terminate normal growth and reproduction cycles to prevent injured cells from proliferating. (foundmyfitness.com)
Cellular senescence is a biologically irreversible state of cell-growth arrest that occurs following either a replicative or an oncogenic stimulus. (elsevierpure.com)
The most common stimulus for senescence is progressive loss of telomeric DNA, which results in the loss of chromosomal stability and eventual unregulated growth and malignancy. (elsevierpure.com)
Senescence is activated through an interaction between the p16 and p53 tumor-suppressor genes. (elsevierpure.com)
Senescent cells can be identified in vitro because they express senescence-associated β-galactosidase, a marker of increased lysosomal activity. (elsevierpure.com)
Cellular senescence plays an integral role in the prevention and development of both benign and malignant gastrointestinal diseases. (elsevierpure.com)
MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. (encyclopedia.pub)
Interestingly, replication stress in Brca2-null cells activates p53 and the expression of its target genes, including senescence-inducing Ink4/Arf. (biomedcentral.com)
This pathway modifies p53 targets, leading to enhanced p53-mediated expression of DUSP4, resulting in cellular senescence. (biomedcentral.com)
Given the previously reported role of DUSP4 as a p53 target, a potential cell cycle checkpoint, and in mediating senescence downstream of replication stress, we hypothesized that DUSP4 may be a critical oncogenic driver in breast cancer. (biomedcentral.com)
Aging kidney and CKD share many common characteristic features with increased cellular senescence, a conserved program characterized by an irreversible cell cycle arrest with altered transcriptome and secretome. (frontiersin.org)
Senescent cells elicit their fibrogenic actions primarily by secreting an assortment of inflammatory and profibrotic factors known as the senescence-associated secretory phenotype (SASP). (frontiersin.org)
Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
In this review, we discuss current understanding of the role and mechanism of cellular senescence in kidney fibrosis. (frontiersin.org)
Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
In this review, we summarize the evidence linking cellular senescence to the pathogenesis of CKD and discuss current understanding of the mechanism and regulators controlling senescence. (frontiersin.org)
Conversely, intact damage can lead to transcription and replication arrest, leading to cell death and senescence (Hoeijmakers, 2009). (villajoyosacf.info)

Compared to HL60 cells, the tyrosine phosphorylation level in K562 cells was markedly increased, suggesting that the increase in tyrosine phosphorylation is due to BCR ABL tyrosine kinase activity, which was confirmed by the expression of BCR ABL shown only in K562 cells. (rafinhibitors.com)
p53 represses the promoter of Polo-like kinase 1, whereas Polo-like kinase 1 inhibits p53 and its family members p63 and p73 in cancer cells lacking functional p53. (oncotarget.com)
Thus, inactive p53 is not associated with a susceptible cytotoxicity of Polo-like kinase 1 inhibition and could rather foster the induction of polyploidy/aneuploidy in surviving cells. (oncotarget.com)
In this regard, restoration of p53 in tumor cells with loss or mutation of p53 will reinforce the cytotoxicity of combined Polo-like kinase 1 therapy and provide a proficient strategy for combating relapse and metastasis of cancer. (oncotarget.com)
The Chk1 kinase and its main upstream activator kinase, ATR, are essential checkpoint effectors in response to a wide variety of genotoxic tensions, and inhibit source firing by focusing on the replication kinases, cyclin-dependent kinase (CDK) and Dbf4-dependent kinase (DDK) [21], while Chk2 and its main upstream activator ATM are primarily associated with the cellular response to double-strand DNA breaks [22]. (ampkpathway.com)
Members of this kinase family have been shown to function in DNA repair and cell cycle checkpoint control following DNA damage. (bmj.com)
Emerging evidence indicate that the mammalian checkpoint kinase ATM induces transcriptional silencing in cis to DNA double-strand breaks (DSBs) through a poorly understood mechanism. (elifesciences.org)

Notably, the G1/S boundary represents a major barrier to cell proliferation and is universally dysfunctional in cancer cells, allowing for the unbridled proliferation observed in malignancy. (intechopen.com)
Combined treatment with selumetinib and a dose of palbociclib sufficient to reinforce G1 arrest in selumetinib-sensitive cells, but not to impair proliferation of resistant cells, delays the emergence of resistant colonies, meaning that escape from G1 arrest is critical in the formation of resistant clones. (babraham.ac.uk)
CIN can promote selective advantage to cancer cells by increasing the probability of novel chromosomal abnormalities, which can change the expression profile of the genes regulating cell division and differentiation, resulting in high proliferation rates [ 3 ] [ 4 ] . (encyclopedia.pub)
Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. (lookformedical.com)
Cell proliferation involves the replication of all cellular contents with the required energy for this to happen. (hindawi.com)
This activation is necessary for both cell proliferation as well as glucose uptake and use. (hindawi.com)
ZKSCAN5-Regulated VEGFC Promotes the Proliferation, Migration, and Tube Formation of HLECs Cancer cell-secreted VEGFC markedly enhanced the proliferation and migration of lymphocyte endothelial cells. (bms-911543.com)
Because ZKSCAN5 improved the secretion of VEGFC by breast cancer cells, the effects of the conditioned medium on HLEC proliferation and migration were investigated in ZKSCAN5 knockdown stable cell lines. (bms-911543.com)
The ZKSCAN5 knockdown ZR75-1 or MDA-MB-231 cell-conditioned medium decreased HLEC proliferation. (bms-911543.com)
The conditioned medium from these cells re-expressing ZKSCAN5 could rescue these effects ( Figures?2A, B ). A similar tendency was also detected in HLEC migration analysis ( Figures?2C, D ). Open in a separate window Figure?2 VEGFC secreted by cancer cells, under the influence of ZKSCAN5, regulates HLEC proliferation, migration, and tube formation. (bms-911543.com)
A, B) Cell proliferation and colony formation assays in HLECs cultured in conditioned medium come from ZR75-1 or MDA-MB-231 cells stably infected with lentivirus carrying ZKSCAN5 shRNA or ZKSCAN5 shRNA plus ZKSCAN5-R. The representative Western blot displays the expression of ZKSCAN5. (bms-911543.com)
Genes that suppress carcinogenesis have been classified as gatekeepers that regulate cellular proliferation and cell death and as caretakers that are primarily encode DNA repair proteins required for the maintenance of genome integrity ( 15 ). (amegroups.org)
The oncoprotein murine double minute 2 (MDM2) promotes cell survival, proliferation, invasion, and therapeutic resistance in many types of cancer. (villajoyosacf.info)

Yao Y, Dai W. Genomic Instability and Cancer. (medium.com)
Defects in DNA damage repair can lead to genomic instability and cancer development. (villajoyosacf.info)

2, 3 Genomic alterations in BRCA1 are found in 40-50% of families with a high incidence of breast cancer (six or more cases), and in a majority (75-80%) of the families that display both breast and ovarian cancers. (bmj.com)
The regulation of DNA repair by the cell cycle is largely the result of chromatin alterations that happen through DNA replication, compression, and dissociation that permit cells to divide effectively [8]. (rockinhibitor.com)
Genomic instability is defined as an increased rate of DNA alterations [ 8 ]. (biomedcentral.com)
Subsequent improved understanding of the molecular alterations present in the cancer cell has enabled the development of targeted therapies for some forms of cancer. (nature.com)
These genetic alterations result in either activation or inactivation of specific gene functions that contribute to the process of carcinogenesis. (bmj.com)
Chromosome instability (CIN) is an increased rate where chromosome acquire alterations due to errors in cell division. (encyclopedia.pub)
Chromosomal instability (CIN) is the increasing rate in which cells acquire new chromosomal alterations. (encyclopedia.pub)

C9orf80: Chromosome 9 open reading frame 80 is a component of the SOSS complex, a multiprotein complex that functions downstream of the MRN complex to promote DNA repair and G2/M checkpoint. (wikipedia.org)
TP53 mutation-associated genomic instability may promote chromosome 7 accumulation and MDR1 amplification during ovarian cancer chemoresistance and recurrence. (biomedcentral.com)
We found that Dusp4 loss alone is insufficient in mediating tumorigenesis, but alternatively converges with loss in Trp53 and MYC amplification to induce tumorigenesis primarily through chromosome 5 amplification, which specifically upregulates Dbf4 , a cell cycle gene that promotes cellular replication by mediating cell cycle checkpoint escape. (biomedcentral.com)
A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. (lookformedical.com)
Table 1 provides a summary outline of the gene symbols, chromosomal locations, radiation sensitivity characteristics, immunodeficiencies, chromosome breakage characteristics, and major cancer risk for each of these disorders. (medscape.com)

Genomic instability caused by mutation of the checkpoint molecule TP53 may endow cancer cells with the ability to undergo genomic evolution to survive stress and treatment. (biomedcentral.com)
We attempted to gain insight into the potential contribution of ovarian cancer genomic instability resulted from TP53 mutation to the aberrant expression of multidrug resistance gene MDR1 . (biomedcentral.com)
Chromosomal instability is a manifest of genome instability with complexities that require careful attention to individual gene control features specific to the cancer cell mutation, tumor microenvironment and surrounding moiety. (medium.com)
Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. (biomedcentral.com)
The BRCA2 R3052W mutation fails to complement chemotherapeutic sensitivity and homology-directed repair functions in BRCA2 knockout cells. (frontiersin.org)
Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
The association between mutation of the ATM gene and a high incidence of lymphoid malignancy in patients with AT, together with the development of lymphoma in Atm deficient mice, supports the proposal that inactivation of the ATM gene may be of importance in the pathogenesis of sporadic lymphoid malignancy. (bmj.com)

The risk is increased 1000-fold for squamous cell carcinoma, basal cell carcinoma, malignant melanoma, and fibrosarcoma and is increased 10-fold to 20-fold for other tumors. (medscape.com)

HER2/neu (also called ERB B2 ) is the gene that encodes the human epidermal growth factor receptor type 2. (cancerquest.org)

This is not a single gene event, there are multiple genes that initiate, control and regulate tumor suppressor function and cell division. (medium.com)
Some proto-oncogenes work to regulate cell death. (cancerquest.org)
This phenomenon, called 'telomeric silencing', or 'telomere position effect' (TPE), was initially discovered and studied using transgenes but it also appears to regulate endogenous subtelomeric genes [ 6 - 8 ]. (biomedcentral.com)
MDM2 can inhibit both p53 and NBS1 to regulate multiple physiological processes and/or induce genomic instability, in which ATM plays a central phosphorylation regulatory role. (villajoyosacf.info)

Further investigations revealed that in vitro cells derived from patients with Nijmegen breakage syndrome display characteristic abnormalities similar to those observed in ataxia-telangiectasia (A-T) , including spontaneous chromosomal instability, sensitivity to ionizing radiation (IR), and radioresistant DNA synthesis (RDS). (medscape.com)
The AT locus was mapped to the chromosomal region 11q22-23 using genetic linkage analysis in the late 1980s and the causative gene was identified by positional cloning several years later. (bmj.com)
These studies unveiled a novel function of DNA-PKcs in safeguarding the genome integrity and cancer suppression as chromosomal instability (CIN) plays an important role in cancer development and is a hallmark of cancer cells ( 14 ). (amegroups.org)
DNA double-strand breaks (DSBs) are particularly dangerous for cells, since their inefficient or inaccurate repair can result in deletions and chromosomal translocations that can lead to cancer and/or severe developmental abnormalities in humans. (elifesciences.org)
In culture, cells from affected individuals exhibit elevated rates of chromosomal breakage or instability, leading to chromosomal rearrangements. (medscape.com)

Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
10 Genes that, when activated, contribute to the carcinogenesis are generally termed proto-oncogenes. (bmj.com)

Using EMBL-EBI, KIAA1958 was found to be overexpressed in pseudopod RNA during the migration of the metastatic cancer cells. (wikipedia.org)
KIAA1958 was also overexpressed in Stat5/ab and stat 3 which are transcription factors reported to be critical for the growth and viability of prostate cancer cells and both the embryonic stem cell and the pluripotent stem cell. (wikipedia.org)
CMB is comprised of more than 30 independent research groups organized in three themes: Cell Biology, Developmental and Stem Cell Biology and Infection and Cancer. (ki.se)
Within the context of DNA double-strand breaks, MUS81 maintainshttp://jcancer.orgJournal of Cancer 2019, Vol.genome stability by forming a heterodimer with Eme1/Mms4 and resolving the Holliday junction (HJ) [6]. (rockinhibitor.com)
Ovarian cancer cell DNA ploidy was determined using Feulgen-stained smears or flow cytometry. (biomedcentral.com)
By using molecular approaches, cell-based and mouse models, we hope to uncover novel tumor suppressors and their modes of action, through which potential therapeutics could be devised to improve cancer treatment. (sinica.edu.tw)
Genomic instability is a hallmark of cancer cells primarily effecting cell division. (medium.com)
MSI is also observed in non small cell lung cancer but the prognosis with this pattern is poor. (medium.com)
In addition, the novel cancer stem cell paradigm raises the prospect of cell-targeted therapies instead of treatment directed against the whole tumour. (nature.com)
DNA repair targeted therapy, which kills cancer cells preventing DNA repair [1-3]. (termedia.pl)
These inhibitors inhibit NHEJ-catalyzed DSB repair and sensitize in vitro cancer cells to DSB-inducing agents. (termedia.pl)
Using a genetically engineered mouse model, we generated mammary-specific Dusp4 -deleted primary epithelial cells to investigate the necessary conditions in which DUSP4 loss may drive breast cancer oncogenesis. (biomedcentral.com)
A diagram showing the major cancer genes for some cancers. (cancerquest.org)
The larger the gene name, the more frequently that gene is defective in that cancer type. (cancerquest.org)
These genes have been found to be either malfunctioning or non-functioning in many different kinds of cancer. (cancerquest.org)
Dr. Pommier also discovered that the natural compound, ecteinascidin 743 (commercialized as Yondelis) and its analog trabectedin acts by alkylating DNA and killing cancer cells by trapping transcription-coupled nucleotide excision repair (TC-NER) (Takebayashi et al, Nature Med 2001). (cancer.gov)
In contrast to normal cells, most cancer cells predominantly produce energy by a high rate of glycolysis followed by lactate fermentation, even in the presence of oxygen, a less efficient metabolism compared to a low rate of glycolysis followed by mitochondrial oxidation of pyruvate [ 2 ]. (hindawi.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)
Metabolic adaptations of cancer cells. (hindawi.com)
Glucose and glutamine are the 2 major substrates used by cancer cells. (hindawi.com)
Statistical Analyses Statistical significance was assessed by using the two-tailed Students in breast cancer cells. (bms-911543.com)
A) Luciferase reporter genes were determined in ZR75-1 and MDA-MB-231 breast cancer cells co-transfected with Glutaminase-IN-1 different concentrations of reporter and myc-ZKSCAN5. (bms-911543.com)
B) Luciferase reporter gene detection in ZR75-1 and MDA-MB-231 breast cancer cells co-transfected with expression in ZR75-1 and MDA-MB-231 cells, which were transfected with ZKSCAN5 shRNA, control shRNA, or ZKSCAN5 shRNA plus shRNA-resistant ZKSCAN5 (ZKSCAN5-R). The representative Western blot further showed the expression of ZKSCAN5. (bms-911543.com)
Genomic instability is a hallmark of cancer and is regulated by the balance between DNA damage and repair (Aguilera and Garcia-Muse, 2013). (villajoyosacf.info)

Loss of proteostasis , the inability of cells to maintain the levels of proteins and enzymes needed for a cell to function correctly. (foundmyfitness.com)
6, 7 BRCA1 interacts with a variety of proteins and is involved in multiple cellular processes including DNA repair, transcription, and checkpoint control. (bmj.com)
11 Both proteins possess an N-terminal RING finger motif and two BRCA1 C-terminal (BRCT) domains present in numerous proteins involved in DNA repair and cell cycle regulation. (bmj.com)
11 The functionally important BARD1/BRCA1 heterodimer formation is mediated by the RING finger motifs and has also been shown to markedly increase the stability of both proteins. (bmj.com)
Cell lysates had been resolved by SDS-PAGE, and proteins had been electro transferred to polyvinylidene fluoride membranes (Millipore, USA). (rockinhibitor.com)
Genome stability is maintained by intricate networks of cell cycle checkpoint proteins. (sinica.edu.tw)
Our main goals are to decipher the molecular basis of checkpoint control by these proteins, their functional relationship with DNA repair and genome maintenance, and the impacts on tumorigenesis. (sinica.edu.tw)
Here, we demonstrate that GFI1 is required in T cells for the regulation of key DNA damage signaling and repair proteins. (bvsalud.org)
Equal partitioning of the plasmid upon host cell division requires plasmid proteins Rep1 and Rep2 and the plasmid STB locus. (bvsalud.org)
To address this issue, primary mouse cells, haploinsufficient for one or two proteins, ATM and RAD9, related to the cellular response to DNA damage were examined. (aacrjournals.org)
The results show that cells having low levels of both ATM and RAD9 proteins are more sensitive to transformation by radiation, have different DNA double-strand break repair dynamics and are less apoptotic when compared with wild-type controls or those cells haploinsufficient for only one of these proteins. (aacrjournals.org)
Our conclusions are that under stress conditions, the efficiency and capacity for DNA repair mediated by the ATM/RAD9 cell signaling network depend on the abundance of both proteins and that, in general, DNA repair network efficiencies are genotype-dependent and can vary within a specific range. (aacrjournals.org)
Most of these genes code for tumor suppressor proteins. (aacrjournals.org)
Another conclusion from most of the cases is that animals or cells haploinsufficient for the specified proteins have higher transformation rates after DNA damage is induced, but when their DNA is not significantly damaged by exogenous sources, tumor development rates are the same as for their wild-type counterparts. (aacrjournals.org)
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)
Cell-cycle kinases DDK and CDK are needed upstream for the activation from the MCM complicated and several PGE1 ic50 research have defined the checkpoint-dependent phosphorylation of MCM proteins [24C27], although certain requirements or results for these adjustments for activity or stability from the helicase still stay unclear. (ampkpathway.com)
In order to investigate the part of MCM PGE1 ic50 proteins in the cellular response to DNA damage, we used shRNA focusing on MCM2 or MCM3 to determine the impact of the reduction in MCM complex within the DDR. (ampkpathway.com)
The alteration of MCM proteins induced a change in the activation of important factors of the DDR in response to Etoposide treatment, including influencing the phosphorylation of -H2AX, CHK1 and CHK2 following Etoposide-induced DNA damage without inducing changes in cell viability, but resulting in a small decrease in DNA replication. (ampkpathway.com)
Results Reducing MCM2 or MCM3 proteins does not impact cell growth Our previous results showed an involvement of MCM proteins in the DNA damage response through its co-localization with -H2AX foci, and through connection with chromatin redesigning proteins in response to DNA damage induced from the topoisomerase II inhibitor Etoposide [28]. (ampkpathway.com)
To investigate the part of the PGE1 ic50 MCM proteins in regulating cell growth as well as investigate the signaling of DNA damage, we used shRNAs delivered Rabbit polyclonal to ACSS2 through lentiviruses focusing on MCM2 (shMCM2) or MCM3 (shMCM3) in the U2OS cell line, as well as a non-silencing control (shControl). (ampkpathway.com)
Note that by convention gene names are italicized and the proteins they make are not. (cancerquest.org)
ATF4 activates the transcription of C/EBP homologous proteins (CHOP), considered to mediate palmitate-induced -cell loss of life [10], [11]. (cgp60474.com)
Activated ATF6 mediates transcription of genes encoding ER chaperone proteins also. (cgp60474.com)
The proteins involved in homologous recombination have to work around other processes that go on inside the nucleus, such as the transcription of DNA in genes into RNA molecules. (elifesciences.org)

additionally, at the finish of mitosis, CyclinB1 is prompted to degrade the complex, enabling cells to complete the replication cycle [10]. (rockinhibitor.com)

Interestingly, Wnt Pathway we found a significant increase in tyrosine phosphorylation at the corresponding molecular weight of hTERT in K562 cells compared to HL60 cells. (rafinhibitors.com)
To evaluate this possibility, hTERT was immunoprecipitated by anti hTERT antibody from both K562 and HL60 cell lysates and resolved by SDS PAGE followed by immunoblotting with anti phosphorylation antibody. (rafinhibitors.com)
We found that hTERT tyrosine phosphorylation was significantly elevated in K562 cells compared to HL60 cells. (rafinhibitors.com)
To further determine whether BCR ABL phosphorylates Raf Inhibitors hTERT, we treated K562 cells with 1 M Gleevec, and evaluated the phosphorylation status of hTERT. (rafinhibitors.com)
As shown in Figure 4c, Gleevec treatment resulted in almost complete inhibition of hTERT phosphorylation at tyrosine residues compared to control cells. (rafinhibitors.com)
To demonstrate that the decrease in tyrosine phosphorylation of hTERT was not due to reduced hTERT expression level, western blot was performed and we did not observe a difference in hTERT expression level in Gleevec treated K562 cells compared to control cells. (rafinhibitors.com)
Gleevec inhibits hTERT nucleoli translocation in K562 BCR ABL positive cells It is known that phosphorylation of hTERT is important for its nuclear translocation. (rafinhibitors.com)
harm affected the phosphorylation of -H2AX, CHK2 and CHK1 without affecting cell viability. (ampkpathway.com)
In normal cells, glucose participates in cellular energy production through glycolysis as well as through its complete catabolism via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS). (hindawi.com)

In particular, ubiquitin-mediated degradation is critically important at transition points where it provides directionality and irreversibility to the cell cycle, which is essential for maintaining genome integrity. (intechopen.com)
Genomic stability is essential in cell maintenance and integrity. (medium.com)
These data suggest that Mrad1 is important for preventing tumor development, probably through maintaining genomic integrity. (biomedcentral.com)

In addition, the effects of reduced Bard1 expression have been studied in murine mammary epithelial cell cultures, where it was associated with complex cellular changes suggestive of a premalignant phenotype. (bmj.com)

In humans, genomic instability is often associated with inherited diseases, predisposition to some cancers, and premature aging. (foundmyfitness.com)

He discovered the indenoisoquinolines as novel Top1 inhibitors, which are in clinical development, and the mitochondrial topoisomerase gene, TOP1mt. (cancer.gov)
DNA2 is also involved in the stability of mitochondrial DNA and the maintenance of telomeres. (longevityfacts.com)

Five members of the Plk family have been discovered in humans and these serine/threonine kinases have emerged as key players by performing crucial functions in the cell cycle, DNA damage response and neuron biology [ 2 - 6 ]. (oncotarget.com)

in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. (diff.org)

The mutated forms of these genes are referred to as oncogenes. (bmj.com)
The normal versions of genes in the first group are called proto-oncogenes. (cancerquest.org)
The mutated or otherwise damaged versions of these genes are called oncogenes. (cancerquest.org)
In normal cells, both internal and external signals control the activity of the oncogenes. (cancerquest.org)
We have two copies of each gene and for oncogenes, a single defective copy is enough to cause a cell to divide. (cancerquest.org)
Numerous genes have been identified as proto-oncogenes. (cancerquest.org)
As stated in the introduction to this section, the defective versions of these genes, known as oncogenes, can cause a cell to divide in an unregulated manner. (cancerquest.org)
The proto-oncogenes that have been identified so far have many different functions in the cell. (cancerquest.org)

As a structure-specific endonuclease, MUS81 is involved in cell cycle regulation and regulates the DNA damage repair approach. (rockinhibitor.com)
These results provide a new insight into the mechanism of PIG3's functioning in DNA damage signaling and the regulation network of cellular DNA-PKcs expression homeostasis. (ijbs.com)

Plk3 is expressed throughout the cell cycle and involved in cellular response to DNA damage [ 9 ]. (oncotarget.com)

MSCs represent a lifelong reservoir for the generation of somatic cells and for cell replacement. (encyclopedia.pub)
In 1998, on the basis of cellular phenotypes and the results of somatic cell complementation studies suggesting genetic heterogeneity, Jaspers et al proposed the term A-T variants for diseases in this group of patients. (medscape.com)

[ 8 ] described a group of patients with an apparently new genetic disorder characterized by microcephaly with normal intelligence, cellular and humoral immune defects, and a striking predisposition to lymphoreticular malignancies. (medscape.com)

Yu-Che Cheng, Sheau-Yann Shieh* Determination of CHK1 Cellular Localization by Immunofluorescence Microscopy Cell Cycle Checkpoints. (sinica.edu.tw)
A concentrated localization of hTERT was observed in nucleoli of non treated K562 cells, but not in HL60 and Jurkat cells. (rafinhibitors.com)
The DUSPs represent a large family of phosphatases [ 9 ] with varying tissue expression, cellular localization and serine/threonine substrates. (biomedcentral.com)

Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. (encyclopedia.pub)

GFI1 is a transcriptional regulator expressed in lymphoid cells, and an "oncorequisite" factor required for development and maintenance of T-lymphoid leukemia. (bvsalud.org)
Here we show that in Saccharomyces cerevisiae a single DSB causes transcriptional inhibition of proximal genes independently of Tel1/ATM and Mec1/ATR. (elifesciences.org)

In mammalian cells, inhibiting the transcription of genes around a double-strand DNA break depends on a signaling pathway that is activated whenever DNA damage is detected. (elifesciences.org)
One of the next challenges will be to see if the resection process makes any contribution to changes in the transcription of genes that surround a double-strand break in mammals as well. (elifesciences.org)

To achieve this, p53 mainly functions as a transcription factor (TF) targeting hundreds of genes, but it also has TF-independent roles in the nucleus and cytoplasm [ 6 ]. (nature.com)
Despite the differences in their normal roles, these genes all contribute to unregulated cell division if they are present in a mutant (oncogenic) form. (cancerquest.org)

This first category also includes genes that contribute to tumor growth by inhibiting cell death. (cancerquest.org)

Key areas of investigation are the identification and functional characterization of stem cell niches in developing tissues and adult organs. (ki.se)
Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19. (stanford.edu)

This research aims at characterizing molecules and signals involved in controlling the undifferentiated state and self-renewal capacity of stem cells, and to develop methods to direct the differentiation of stem cells into clinically relevant cell types. (ki.se)
Basic genetic and molecular biology methodologies are combined with complementary bioinformatic and genome-wide approaches, allowing investigation global molecular changes in cells in various differentiation processes. (ki.se)
These cells possess both differentiation plasticity (stemness) and tissue supportive functions (stromalness) that can coexist and overlap, with differences depending on tissue source, donor characteristics, culture conditions and delivery strategies, leading to alternative best fittings for the term "stem" or "stromal" [ 7 ] . (encyclopedia.pub)

Dr. Cong's group is developing novel genome technology for genome engineering and single-cell genomics, leveraging scalable computational methods. (stanford.edu)

4 - 7 The ATM gene encodes a nuclear phosphoprotein of approximately 350 kDa (3056 amino acids) and is ubiquitously expressed. (bmj.com)

The current models for CIN involve telomere dysfunction, defective spindle assembly, sister chromatid cohesion, DNA double-strand breaks (DSB) repair, genes involved in the cell cycle, and epigenetic regulators. (encyclopedia.pub)
Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends. (lookformedical.com)

In response to genotoxic stress, either extrinsic such as ionizing radiation-induced DNA breaks or intrinsic such as oxidative damage, a cascade of signaling events are initiated to arrest the cell cycle, eliminate damaged cells, or to repair the damage. (sinica.edu.tw)
Selumetinib causes long-term G1 arrest accompanied by reduced expression of DNA replication and repair genes, but cells stochastically re-enter the cell cycle during treatment despite continued repression of pERK1/2. (babraham.ac.uk)
The tumor suppressor gene p53 regulates cell cycle arrest to allow time for DNA repair. (villajoyosacf.info)

Thermal stability assays show that ERKi do not destabilise ERK2 (or ERK1) in vitro, suggesting that ERK2 turnover is a cellular consequence of ERKi binding. (babraham.ac.uk)
Cells grown in vitro from neoplastic tissue. (lookformedical.com)

The long-term vision is that the delineation of key developmental strategies, and identification of molecules involved in these processes, will provide new paradigms in cellular transplantation and regenerative medicine. (ki.se)
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis. (lookformedical.com)

Component of the BRCA1-RBBP8 complex which regulates CHEK1 activation and controls cell cycle G2/M checkpoints on DNA damage via BRCA1-mediated ubiquitination of RBBP8. (helixlabs.ai)

The genes in the second group are called tumor suppressors. (cancerquest.org)

During aging of the organism, MSCs also age, and this implies an impairment of stem cell functions contributing to the progressive decrease in tissue maintenance and repair, a characteristic of the aging process. (encyclopedia.pub)
DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. (biomedcentral.com)
It is a tumor suppressor gene, involved in DNA DSB repair through the process of homologous recombination [16]. (termedia.pl)
P53 deficiency results in reduced repair activity and decreased cell survival after UV-induced DNA damage, suggesting the involvement of p53 in nucleotide excision repair (NER) (Smith et al. (villajoyosacf.info)

ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
On the contrary, enhanced glycolysis could be linked to the cell death observed 48 hours after imatinib withdrawal as inhibition of glycolysis by 2 deoxyglucose completely rescued cells from imatinib withdrawal induced death. (rafinhibitors.com)
A significant, although incomplete, inhibition of cell death was also observed upon partial deprivation of glutamine from the medium and inhibition Celastrol of glutaminase activity using the glutaminase inhibitor 6 diazo 5 oxo l norleucine. (rafinhibitors.com)

Specifically, the concepts of tumour heterogeneity, oncogene addiction, non-oncogene addiction, tumour initiating cells, tumour microenvironment, non-coding sequences and DNA damage response will be reviewed. (bmj.com)
The former include hypoxia, high lactate levels or the abundance of growth factors within the cellular microenvironment. (springer.com)

Loss of heterozygosity at 11q22-23 (the location of the ATM gene) is a common event in lymphoid malignancy. (bmj.com)

After overnight culture, the cells were exposed to 2400 Joules UV irradiation (right image) or untreated (left image) and then allowed to recover for 30-60 minutes at 37°C. The cells were fixed, permeabilized with cold methanol, and stained with Purified Mouse anti-H2AX (pS139) followed by Alexa Fluor® 488 goat anti-mouse IgG (Invitrogen, Cat. (bdbiosciences.com)
Required for appropriate cell cycle arrests after ionizing irradiation in both the S-phase and the G2 phase of the cell cycle. (helixlabs.ai)
J-H Lee et al extensively investigated the participation of PIG3 in DNA damage checkpoints after UV irradiation or after treatment using the radiomimetic drug neocarzinostatin (NCS) ( 8 ). (ijbs.com)

(B) Western blot of total cellular lysates from DLD-1 BRCA2 −/− cells stably transfected with full-length BRCA2 cDNA constructs: BRCA2 Wild Type (WT) and BRCA2 R3052W (1 and 2 correspond to two independent clones). (frontiersin.org)
(F) Western blot of total cellular lysates from DLD-1 parental cells (these cells express a wild-type allele of BRCA2) stably transfected with R3052W (3 and 5 correspond to two independent clones) full-length 2XMBP-BRCA2 cDNA constructs. (frontiersin.org)

These three cell lines were infected with GFPhTERT as the endogenous level of hTERT could not easily be detected in these cells by immunofluoresence microscopy. (rafinhibitors.com)

The tumor suppressor TP53 (also called p53) has been among the most extensively studied genes since its discovery in 1979 [ 1 , 2 ]. (nature.com)

Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)
We summarize a large amount of clinical data on this gene here. (helixlabs.ai)

Anatomy23

Organisms5

Diseases12

Chemicals and Drugs101

Analytical, Diagnostic and Therapeutic Techniques and Equipment26

Phenomena and Processes102

Disciplines and Occupations1

Information Science3

Health Care4

Mutations26

Pathways16

Progression13

Mechanisms18

Maintains genomic stability1

Breast and ovarian cancer susceptibility genes1

Apoptosis21

Protein32

Maintenance of genomic3

Susceptibility5

Senescence17

Kinase7

Proliferation13

Instability and Cancer2

Alterations7

Chromosome5

Mutation7

Malignant1

Epidermal growth f1

Regulate4

Chromosomal5

Carcinogenesis2

Cancer24

Proteins24

Mitosis1

Phosphorylation9

Integrity3

Phenotype1

Cancers1

Mitochondrial2

Kinases1

Chromosomes1

Oncogenes8

Regulation2

Response to DNA damage1

Somatic2

Predisposition1

Localization3

Homeostasis1

Transcriptional2

Transcription of genes2

Roles2

Contribute to tumor1

Functional2

Differentiation3

Methods1

Encodes1

Telomere2

Arrest3

Vitro2

Processes2

Ubiquitination1

Tumor suppressors1

Repair4

Inhibition3

Microenvironment2

Malignancy1

Irradiation3

Lysates2

Endogenous1

TP531

Clinical2