• The checkpoint pathways regulate cell-cycle transition, induce tolerance by up-regulating and recruiting special polymerases (translesion polymerases) onto chromatin for mutagenic synthesis to tolerate the stress and to facilitate replication fork re-start, also can regulate an endonuclease to prevent deleterious genomic rearrangement, or in some cases to induce apoptosis. (wikipedia.org)
  • The MRN complex plays a critical role in maintaining the stability of genetic material, as it is involved in crucial DNA repair pathways and cell cycle checkpoints. (tangut.net)
  • 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)
  • 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)
  • [3] Cellular checkpoints and DNA damage-response pathways help preserve genomic stability and cell-cycle progression, but these processes decline with aging. (foundmyfitness.com)
  • Therefore, there are multiple conserved pathways within cells that respond to such errors by recruiting DNA repair processes or initiating apoptosis. (medium.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)
  • 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)
  • 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)
  • However, biologically a gene or a sample could participate in multiple biological pathways, and a cellular process is generally active only under a subset of genes or experimental conditions. (columbiagypsy.net)
  • 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)
  • Enriched pathways analysis of these positively correlated genes featured Toll-like receptor and SUMOylation pathways. (preprints.org)
  • Cells have evolved with conserved recombination mediated genome editing pathways as a mean for repairing DSBs and restarting replication forks, thus allowing genome duplication to continue [ 8 ]. (springeropen.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)
  • In this review, we showcase recent studies on the splicing and AS of key genes in metabolic pathways in the liver, the effect of metabolic signals on the spliceosome, and therapeutic intervention points based on RNA splicing. (imperial.ac.uk)
  • Her genetic studies of fission yeast had found that mutations in replication genes often induce mutator phenotypes. (wikipedia.org)
  • In this article, we will take a closer look at the RAD50 gene and its importance, learn about the various types of RAD50 gene mutations, and explore the key risk factors and symptoms associated with these mutations . (tangut.net)
  • RAD50 gene mutations can lead to a variety of defects that disrupt the normal functioning of the MRN complex, thus affecting DNA repair, recombination, and genome stability. (tangut.net)
  • Changes or abnormalities in this gene can occur as a result of genetic inheritance, exposure to toxins or radiation, or through spontaneous mutations. (tangut.net)
  • 3. Frameshift Mutations: These mutations occur when the addition or deletion of nucleotides in the RAD50 gene shifts the reading frame of the genetic code, leading to an altered protein structure and function. (tangut.net)
  • 5. Splice-Site Mutations: These mutations affect the way in which the RAD50 gene is processed during mRNA production, leading to altered protein synthesis. (tangut.net)
  • RAD50 gene mutations can increase the risk of various cancers and other health issues. (tangut.net)
  • Individuals with a positive family history of cancer or other genetic disorders are at higher risk of carrying RAD50 gene mutations. (tangut.net)
  • Exposure to environmental toxins or radiation may also increase the likelihood of gene mutations. (tangut.net)
  • RAD50 gene mutations can be diagnosed through genetic testing, which involves analyzing DNA samples for abnormalities in the RAD50 gene sequence. (tangut.net)
  • Treatment options for RAD50 gene mutations depend on the specific type of mutation and associated symptoms. (tangut.net)
  • 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)
  • Thus, somatic mutations, and the consequent genomic instability may be an important driving force for the development of chemoresistance in malignant tumors. (biomedcentral.com)
  • 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)
  • 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)
  • Cancer genome sequencing reveals diverse acquired mutations in CTCF , which we have shown, functions as a tumour suppressor gene. (preprints.org)
  • 3] Patients are classified into one of two distinct categories based on the presence or absence of mutations in the IDH1 or IDH2 genes. (cancernetwork.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)
  • An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional. (lookformedical.com)
  • Genetic testing for deleterious mutations in breast cancer 1, early onset gene ( BRCA1 ) and BRCA2 can provide key information to guide clinical decision making. (jci.org)
  • Women who are heterozygous carriers of mutations in either gene have a 60%-80% lifetime risk of breast cancer and a 10%-40% lifetime risk of ovarian cancer ( 1 ), reflecting a very high penetrance. (jci.org)
  • 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)
  • Eukaryotic cells have developed exquisite mechanisms that monitor and coordinate cell cycle progression with repair of DNA damage to maintain genome integrity. (biomedcentral.com)
  • The encoded protein plays a role in many cellular processes including cell cycle progression, DNA repair and apoptosis by regulating the activity of protein phosphatase 1. (nih.gov)
  • 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)
  • Accumulating evidence shows that cancer stem cells are key drivers of tumor formation, progression, and recurrence. (hindawi.com)
  • Molecular portraits of cell cycle checkpoint kinases in cancer evolution, progression, and treatment responsiveness. (uc.edu)
  • 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)
  • 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)
  • For instance, DNA replication and DNA damage checkpoints delay cell cycle progression until each chromosome is fully replicated and physically intact. (rupress.org)
  • Finally, CAFs promote cancer progression and act in cancer cell drug resistance. (spandidos-publications.com)
  • 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)
  • 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)
  • 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)
  • It is known to halt cancer cell proliferation and the propagation of DNA damage and can also initiate DNA repair mechanisms. (medium.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)
  • 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)
  • 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)
  • 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)
  • 1] 'Multiforme,' which refers to a heterogenous histologic appearance and proliferation of multiple cell types, was abandoned from the revised nomenclature in the 2007 World Health Organization Classification of Tumors of the Central Nervous System, and is now simply called 'glioblastoma. (cancernetwork.com)
  • 2] Glioblastoma is histologically defined by neoplastic cells with astrocytic characteristics and the presence of either endothelial proliferation-often in a glomeruloid morphology-and/or necrosis, which may resemble a pseudopalisading pattern (a false fence of neoplastic cells surrounding an area of necrotic tissue). (cancernetwork.com)
  • The oncoprotein murine double minute 2 (MDM2) promotes cell survival, proliferation, invasion, and therapeutic resistance in many types of cancer. (villajoyosacf.info)
  • Cellular senescence is a stress response of mammalian cells leading to a durable arrest of cell proliferation that has been implicated in tumor suppression, wound healing, and aging. (biomedcentral.com)
  • the end result of these defects is genomic instability, decreased cell proliferation, and premature cell senescence and death. (medscape.com)
  • AP4 presumably contributes to the phenotype of cancer cells by activating or repressing genes that harbor CAGCTG elements in their promoter regions, thereby controlling processes such as proliferation, metabolism, apoptosis, epithelial-mesenchymal transition (EMT) and metastasis [ 5 ]. (biomedcentral.com)
  • CAFs provide cancer cells with nutrition and promote the proliferation, invasion and metastasis of cells ( 6 - 9 ). (spandidos-publications.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)
  • 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)
  • 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)
  • 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)
  • 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)
  • Is p53-dependent ferroptosis sufficient for tumor suppression in the absence of cell cycle arrest, senescence, and apoptosis? (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)
  • Detection of merely apoptosis does not reveal the type of central nervous system (CNS) cells that are dying in the CNS diseases and injuries. (bvsalud.org)
  • In situ detection and estimation of amount of apoptosis specifically in neurons or glial cells (astrocytes, oligodendrocytes, and microglia) can unveil valuable information for designing therapeutics for protection of the CNS cells and functional recovery. (bvsalud.org)
  • A method was first developed and reported from our laboratory for in situ detection and estimation of amount of apoptosis precisely in neurons and glial cells using in vitro and in vivo models of CNS diseases and injuries. (bvsalud.org)
  • This is a combination of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and double immunofluorescent labeling (DIFL) or simply TUNEL-n-DIFL method for in situ detection and estimation of amount of apoptosis in a specific CNS cell type. (bvsalud.org)
  • A primary anti-NeuN (neurons), anti-GFAP (astrocytes), anti-MBP (oligodendrocytes), or anti-OX-42 (microglia) IgG antibody and a secondary IgG antibody conjugated with one of the above fluorophores (other than that of ani-DIG antibody) are used for in situ detection of apoptosis in a specific CNS cell type in the mixed culture and animal models of the CNS diseases and injuries. (bvsalud.org)
  • Apoptosis can occur due to the overproduction of apoptotic proteins under the influence of external trigger or due to the overexpression of the apoptotic genes. (bvsalud.org)
  • Unlike apoptosis, senescence is a state of which cells are still alive and metabolically active. (frontiersin.org)
  • 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)
  • A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.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)
  • Her scientific pursuit focuses on the biochemical mechanisms of chromosome replication proteins, and molecular mechanisms of their involvement in maintaining genome integrity during chromosome replication. (wikipedia.org)
  • 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)
  • consequently cells have evolved a variety of mechanisms to repair double-strand breaks (DSBs). (brandeis.edu)
  • 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)
  • Homologous recombination' is one of the main mechanisms used by cells to repair DNA double-strand breaks. (elifesciences.org)
  • While the contribution of these mechanisms to cell and tissue identity is widely accepted, their role in physiological and pathological contexts within tissues is just beginning to be appreciated. (imperial.ac.uk)
  • 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)
  • 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 proliferative arrest is mediated by transcriptional repression of genes essential for cell division by the retinoblastoma protein family. (biomedcentral.com)
  • In mammals, X chromosome dosage compensation involves heterochromatization and transcriptional silencing of one of two copies of the X chromosome in female cells. (biomedcentral.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)
  • 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)
  • Recent studies into pre-mRNA splicing and alternative splicing (AS) and their effects on gene expression have revealed considerable transcriptional complexity in the liver, both in health and disease. (imperial.ac.uk)
  • We previously identified the AP4 gene as a direct transcriptional target of c-MYC [ 4 ]. (biomedcentral.com)
  • A total of 7 possible genetic alterations and epigenetic changes in CAFs are discussed, including gene differential expression, karyotype analysis, gene copy number variation, loss of heterozygosis, allelic imbalance, microsatellite instability, post‑transcriptional control and DNA methylation. (spandidos-publications.com)
  • Of the 31 genes, the 21 upregulated genes were primarily associated with cell paracrine and intracellular signaling, transcription regulation and cell adhesion and migration, and their transcriptional products included transforming growth factor-β2 (TGF-β2), insulin-like growth factor-binding protein 2 and transcriptional factor AP-2α/γ ( 11 ). (spandidos-publications.com)
  • The RAD50 gene codes for a protein that is part of a highly conserved protein complex called Mre11-Rad50-NBS1 (MRN). (tangut.net)
  • 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)
  • This gene encodes a protein phosphatase 1 binding protein. (nih.gov)
  • MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability. (nih.gov)
  • 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)
  • 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)
  • D) Cytoplasmic and nuclear ZKSCAN5 protein levels in two types of breast cancer cell lines, ZR75-1 and MDA-MB-231. (bms-911543.com)
  • 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)
  • 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)
  • Microtubule-associated protein MAP1LC3C regulates lysosomal exocytosis and induces zinc reprogramming in renal cancer cells. (uc.edu)
  • 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)
  • A recurring problem in the clinic is that many detectable changes within the BRCA1 gene produce subtle alterations to the protein that are not easily recognized as either harmful (loss-of-function) alleles or harmless and thus inconsequential polymorphisms. (jci.org)
  • 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)
  • 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)
  • The G 2 gap phase further separates S-phase from mitosis, allowing for continued cell growth and maturation before cell division. (rupress.org)
  • Thus, the products of chromosome replication (sister chromatids) generated during S-phase must be identified over time until mitosis when sisters associate with the mitotic spindle and segregate away from each other into the newly forming daughter cells. (rupress.org)
  • 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)
  • 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)
  • However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. (springeropen.com)
  • Failure to repair DSBs can lead to unwanted consequences, such as loss of genetic information, chromosomal rearrangements and even cell death. (springeropen.com)
  • The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. (lookformedical.com)
  • A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. (lookformedical.com)
  • 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)
  • Immunofluorescence, chromosome and micronuclei enumeration, MTT and colony formation assays were used to determine the effects of AP4 inactivation and target gene regulation on chromosomal instability (CIN) and drug sensitivity. (biomedcentral.com)
  • Inactivation of AP4 in CRC cell lines resulted in increased spontaneous and c-MYC-induced DNA damage, chromosomal instability (CIN) and cellular senescence. (biomedcentral.com)
  • In culture, cells from affected individuals exhibit elevated rates of chromosomal breakage or instability, leading to chromosomal rearrangements. (medscape.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)
  • It is widely recognized that the accumulation of various harmful genetic alterations in normal cells may induce malignant cancer cells ( 1 ). (spandidos-publications.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)
  • Yu-Che Cheng, Sheau-Yann Shieh* Determination of CHK1 Cellular Localization by Immunofluorescence Microscopy Cell Cycle Checkpoints. (sinica.edu.tw)
  • Cells are constantly exposed to stresses from cellular metabolites as well as environmental genotoxins. (biomedcentral.com)
  • Cellular senescence , the process by which damaged cells terminate normal growth and reproduction cycles to prevent injured cells from proliferating. (foundmyfitness.com)
  • 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)
  • (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)
  • 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)
  • 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)
  • Cellular senescence is characterized by an irreversible and permanent cell cycle arrest coupled with altered transcriptome and secretome. (frontiersin.org)
  • Plk3 is expressed throughout the cell cycle and involved in cellular response to DNA damage [ 9 ]. (oncotarget.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)
  • this limitation has been overcome via ectopic expression of human telomerase reverse transcriptase (hTERT), the catalytic component of telomerase, to produce large quantities of these cells as an attractive source for cellular transplantation [ 16 - 18 ]. (hindawi.com)
  • This receptor is found in moderate levels on some normal cells and as the gene's name implies, it is involved in cellular responses to growth factors. (cancerquest.org)
  • In humans, genomic instability is often associated with inherited diseases, predisposition to some cancers, and premature aging. (foundmyfitness.com)
  • Human genomic databases including The Cancer Genome Atlas (TCGA) were interrogated to identify DPP9 LoF variants and associated cancers. (preprints.org)
  • A diagram showing the major cancer genes for some cancers. (cancerquest.org)
  • Clinical activity of TIL therapy has also been reported in other cancer types, including human papillomavirus-associated cancers, cholangiocarcinoma, non-small-cell lung cancer (NSCLC), and triple-negative breast cancer (TNBC). (biomedcentral.com)
  • MSC use frequently requires in vitro expansion, thus exposing cells to replicative senescence. (encyclopedia.pub)
  • 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)
  • Conversely, intact damage can lead to transcription and replication arrest, leading to cell death and senescence (Hoeijmakers, 2009). (villajoyosacf.info)
  • SIRT2, an NAD-dependent class III histone deacetylase, contributes to H4-K16Ac deacetylation and DNA compaction in human fibroblast cell lines that assemble striking senescence-associated heterochromatin foci (SAHFs). (biomedcentral.com)
  • Decreased H4-K16Ac was observed in both replicative and oncogene-induced senescence of these cells. (biomedcentral.com)
  • In contrast, this mechanism was inoperative in a fibroblast cell line that did not assemble extensive heterochromatin during senescence. (biomedcentral.com)
  • Variable DNA compaction observed during senescence is explained in part by cell-type specific regulation of H4 deacetylation and HMGA1/2 expression. (biomedcentral.com)
  • Deacetylation of H4-K16Ac during senescence may explain reported decreases in this mark during mammalian aging and in cancer cells. (biomedcentral.com)
  • Inhibition of miR-22-3p or ectopic MDC1 expression reversed the increased senescence, DNA damage, CIN and defective HR observed in AP4 -deficient CRC cells. (biomedcentral.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)
  • The present review summarizes the recent achievements in understanding the gene profiles of CAFs and pays special attention to their possible epigenetic alterations. (spandidos-publications.com)
  • Genetic alterations include genetic mutation, gene copy number variation (CNV), loss of heterozygosity (LOH), allelic imbalance (AI) and microsatellite instability (MSI). (spandidos-publications.com)
  • Unrepaired DNA lesions can lead to cell death, gene mutation and cancer. (biomedcentral.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)
  • TP53 mutation-associated genomic instability may promote chromosome 7 accumulation and MDR1 amplification during ovarian cancer chemoresistance and recurrence. (biomedcentral.com)
  • The BRCA2 R3052W mutation fails to complement chemotherapeutic sensitivity and homology-directed repair functions in BRCA2 knockout cells. (frontiersin.org)
  • Up to 10% of patients with glioblastoma harbor a mutation in the IDH1 or IDH2 genes, an early event in gliomagenesis. (cancernetwork.com)
  • Sequence analysis of these genes is being used to identify BRCA1/2 mutation carriers, though these efforts are hampered by the high frequency of variants of unknown clinical significance (VUSs). (jci.org)
  • Individuals carrying a mutation in the breast cancer 1, early onset gene ( BRCA1 ) are at increased risk of breast or ovarian cancer and thus are candidates for risk reduction strategies such as oophorectomy and mastectomy. (jci.org)
  • We have shown that this regulation involves the action of a small Recombination Enhancer (RE) sequence that enables a donor on the left chromosome arm to recombine preferentially in MATa cells. (brandeis.edu)
  • The construction of this cell line is the first promising step in the regulation of GAL secretion from hTERT-immortalized BMSCs, and the potential application of this system may provide a stem cell-based research platform for pain. (hindawi.com)
  • Furthermore, we used this assay to determine the effects of BRCA1 variants on cell cycle regulation, differentiation, and genomic stability. (jci.org)
  • 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)
  • Plk1 inhibitors target all rapidly dividing cells irrespective of tumor cells or non-transformed normal but proliferating cells. (oncotarget.com)
  • is usually regulated by inhibitors and activators, then Open in a separate window Figure 3 The Simulated dataset with realistic character types represents the abundance of the mRNA of gene are inhibitor concentrations, are activator concentrations, and is usually mRNA breakdown rate. (columbiagypsy.net)
  • This has led to the need for new immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and novel immune checkpoint inhibitors. (biomedcentral.com)
  • The clinical success of immune checkpoint inhibitors has dramatically changed outcomes for patients across cancer types. (biomedcentral.com)
  • This has resulted in the development of additional immunotherapy-based approaches, including adoptive cell transfer (ACT), therapeutic vaccines, and inhibitors of other immune checkpoints. (biomedcentral.com)
  • This improvement may be a consequence of the introduction of immune-checkpoint-inhibitors and other targeted treatments for metastatic and unresectable disease. (cdc.gov)
  • 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)
  • Rad1 plays crucial roles in DNA repair and cell cycle checkpoint control, but its contribution to carcinogenesis is unknown. (biomedcentral.com)
  • 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)
  • 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)
  • Integrative analysis of functional genomic screening and clinical data identifies a protective role for spironolactone in severe COVID-19. (stanford.edu)
  • In this study we developed a functional assay using mouse ES cells to study variants of BRCA1. (jci.org)
  • Our results demonstrate that this ES cell-based assay is a powerful and reliable method for analyzing the functional impact of BRCA1 variants, which we believe could be used to determine which patients may require preventative treatments. (jci.org)
  • Here a DSB at the MAT locus is created by a site specific HO endonuclease, which we can induce synchronously in a large population of cells. (brandeis.edu)
  • 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)
  • Dr. Wang was a member of several professional organizations, including the American Society for Biochemistry and Molecular Biology, the American Society for Microbiology, the American Society for Cell Biology, and the American Association for Cancer Research Inc. She had served as the principal investigator of three National Institute of Health/ National Cancer Institute supported programs. (wikipedia.org)
  • 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)
  • Ovarian cancer cell DNA ploidy was determined using Feulgen-stained smears or flow cytometry. (biomedcentral.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)
  • 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)
  • 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)
  • We also elaborate on the potential of targeting HR genes for cancer therapy and anticancer strategies. (springeropen.com)
  • 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)
  • The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022), organized by the Fondazione Melanoma Onlus, Naples, Italy, in collaboration with the Society for Immunotherapy of Cancer. (biomedcentral.com)
  • The study and/or manipulation of administered cells can potentially result in identification of the exact cell subpopulations and effector functions required for cancer regression in vivo. (biomedcentral.com)
  • Here, we set out to determine the relevance of AP4 in human colorectal cancer (CRC) cells. (biomedcentral.com)
  • To date, inheritance of a mutant BRCA1 or BRCA2 gene is the best-established indicator of an increased risk of developing breast cancer. (jci.org)
  • CAFs maintain their phenotype for numerous passages during culture in vitro without exposure to cancer cells, while NFs cannot be infinitely proliferous like cancer cells ( 10 ). (spandidos-publications.com)
  • Recombination between homologous sequences is a fundamentally important process both in meiosis and in mitotic cells. (brandeis.edu)
  • To this end we have expressed the site-specific HO endonuclease in meiotic cells so that we can compare recombination events at the same loci where we have used HO to stimulate recombination in mitotic cells. (brandeis.edu)
  • Using synchronized cells undergoing recombination that is initiated at a specific site on a chromosome by an inducible endonuclease, we use physical monitoring techniques (Southern blots, PCR analysis) to follow the sequence of molecular events that occur in real time. (brandeis.edu)
  • The two donor loci are maintained in a chromatin configuration that prevents them from being transcribed or being cleaved by the HO endonuclease that cuts the same sequence at MAT to initiate switching. (brandeis.edu)
  • Non-homologous end joining (NHEJ), which does not depend upon sequence homology, is the key repair pathway during the G0/G1 stages of the cell cycle [ 10 ]. (springeropen.com)
  • The cell division process is dependent on a tightly controlled sequence of events. (cancerquest.org)
  • The availability of the functionally active recombinant human DNA polymerase alpha has allowed the findings of how the this polymerase interacts with the initiation proteins of several pathogenic DNA viruses such as SV40, BPV, HPV-11, and herpes simplex virus type 1 to initiate the viral DNA replication in human cells. (wikipedia.org)
  • Genome stability is maintained by intricate networks of cell cycle checkpoint proteins. (sinica.edu.tw)
  • 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)
  • Loss of proteostasis , the inability of cells to maintain the levels of proteins and enzymes needed for a cell to function correctly. (foundmyfitness.com)
  • Thus, the imbalance in the production of apoptotic proteins can be quantified using the Western blotting technique and the overexpression of apoptotic genes in hippocampal DNA can be quantified using the real-time quantification of mRNA expression of the apoptotic proteins. (bvsalud.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)
  • Note that by convention gene names are italicized and the proteins they make are not. (cancerquest.org)
  • 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)
  • By contrast, the 10 downregulated genes were primarily associated with epithelial membrane proteins ( 11 ). (spandidos-publications.com)
  • She used a model organism, fission yeast (Schizosaccharomyces pombe), taking a genetic, biochemical, and cell biology approach for the studies. (wikipedia.org)
  • 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)
  • Background Clustering gene expression data has been an important problem in computational biology. (columbiagypsy.net)
  • Using this database, researchers can quickly retrieve the expression level data for target genes in different tissues and in response to different treatments to elucidate gene functions and explore the biology of rapeseed at the transcriptome level. (preprints.org)
  • Applying the BBC algorithm to the yeast expression data, we noticed that most the biclusters we discovered are backed by significant biological evidences, such as for example enrichments of gene features and transcription aspect binding sites in the corresponding promoter sequences. (columbiagypsy.net)
  • The BBC model can simply handle lacking data via Monte Carlo imputation and gets the potential to end up being extended to integrated study of gene transcription networks. (columbiagypsy.net)
  • These events are dependent on the proper levels of transcription and translation of certain genes. (cancerquest.org)
  • Previous research has reported that forming a double-strand break in the DNA reduces the levels of transcription for the genes that surround the break, but it was not clear how this occurred. (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)
  • AP4 (TFAP4) encodes a basic helix-loop-helix leucine zipper (bHLH-LZ) transcription factor and is a direct target gene of the oncogenic transcription factor c-MYC. (biomedcentral.com)
  • Due to the low abundance of MSCs in human adult tissues (about 1/10 6 cells in adult bone marrow and 1/10 3-4 cells in adipose tissue and umbilical cord) [ 16 ] , frequently ex-vivo expansion precedes therapeutic administration, to obtain a clinically relevant number of cells. (encyclopedia.pub)
  • Development of new or improved laboratory/experimental techniques, instruments, or supporting software that measure the location and dynamics of molecules in situ, and organelles, cells, or tissues on the nanometer and micrometer length scales. (nih.gov)
  • Mechanochemical Principles of Spatial and Temporal Patterns in Cells and Tissues. (mpi-cbg.de)
  • Patterns are ubiquitous in living systems and underlie the dynamic organization of cells, tissues, and embryos. (mpi-cbg.de)
  • Overexpression of R3052W in DLD1 parental BRCA2 wild-type cells confers sensitivity to MMC DNA damage. (frontiersin.org)
  • High expression of genes that positively correlated with overexpression of DPP4, DPP8, and DPP9 were associated with very poor survival in HCC. (preprints.org)
  • 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)
  • Paralog-specific signaling by IRAK1/4 maintains MyD88-independent functions in MDS/AML. (uc.edu)
  • 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)
  • These data suggest that Mrad1 is important for preventing tumor development, probably through maintaining genomic integrity. (biomedcentral.com)
  • To determine whether Rad1 functions to maintain genomic stability and prevent tumor development, we generated Mrad1 mutant mice by gene targeting. (biomedcentral.com)
  • The plaid model [5] introduces a statistical model assuming that the expression value in a bicluster is the sum of the main effect, the gene effect, the condition effect, and the noise term, i.e. (columbiagypsy.net)
  • We determined the expression patterns of 101,040 genes via FPKM analysis and displayed the results using the eFP browser. (preprints.org)
  • We used this information to develop the BrassicaEDB, including eFP, Treatment, Coexpression, and SRA Project modules based on gene expression profiles and Gene Feature, qPCR Primer, and BLAST modules based on gene sequences. (preprints.org)
  • The BrassicaEDB provides comprehensive gene expression profile information and a user-friendly visualization interface for Brassica crop researchers. (preprints.org)
  • All four DPP4-like genes were overexpressed in liver tumours and their joint high expression was associated with poor survival in HCC. (preprints.org)
  • We also analysed the impact of CTCF haploinsufficiency by examining gene expression changes in CTCF -altered endometrial carcinoma. (preprints.org)
  • A CRISPR/Cas9 approach was employed to generate AP4 -deficient CRC cell lines with inducible expression of c-MYC. (biomedcentral.com)
  • AP4 -deficient cells displayed increased expression of the long non-coding RNA MIR22HG, which encodes miR-22-3p and was directly repressed by AP4. (biomedcentral.com)
  • Furthermore, Mediator of DNA damage Checkpoint 1 ( MDC1 ), a central component of the DNA damage response and a known target of miR-22-3p, displayed decreased expression in AP4 -deficient cells. (biomedcentral.com)
  • The prostaglandin-endoperoxide synthase 2 gene (PTGS2), which encodes cyclooxygenase-2, was found to upregulate the expression of TGF-β2 ( 14 ). (spandidos-publications.com)
  • These results are consistent with another study concerning the gene expression profiling of breast CAFs, which were detected using a complementary DNA microarray ( 15 ). (spandidos-publications.com)
  • and the cells' response to chromosome replication stress and DNA damage to maintain genomic stability. (wikipedia.org)
  • Her lab was the first to use reverse-genetic approach to isolate the cDNA clones encoding the catalytic polypeptide of the principal chromosome replication initiation enzyme, DNA polymerase alpha, of human cells. (wikipedia.org)
  • Dr. Wang's lab also investigated how cells respond to chromosome replication stress and DNA damage to maintain the cells' genomic stability. (wikipedia.org)
  • Her research is focused on understanding how cells respond to DNA damage and safeguard the integrity of the genome. (mdanderson.org)
  • Genomic stability is essential in cell maintenance and integrity. (medium.com)
  • Microsatellite integrity in the genome is believed to be maintained by the mismatch repair (MMR) system, which corrects single base mismatches and insertion-deletion loops on the nascent DNA strand ( Kunkel 1995 ). (medium.com)
  • The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. (imperial.ac.uk)
  • Among these unconventional activities, an iron-dependent form of non-apoptotic cell death, termed ferroptosis, attracts great interest. (nature.com)
  • An anti-digoxigenin (DIG) IgG antibody conjugated with 7-amino-4-methylcoumarin-3-acetic acid (AMCA) for blue fluorescence, fluorescein isothiocyanate (FITC) for green fluorescence, or Texas Red (TR) for red fluorescence can be used for in situ detection of apoptotic cell DNA, which is earlier labeled with TUNEL using alkali-stable DIG-11-dUTP. (bvsalud.org)
  • Indeed, the potent pathotropic migratory properties of BMSCs and ability to circumvent both the complications associated with immune rejection of allogenic cells and many of the moral reasons associated with embryonic stem cell use suggest that BMSCs are most promising stem cells as a potential target for the clinical use of genetically engineered stem cells [ 14 , 15 ]. (hindawi.com)
  • The use of cell therapies, drivers of immune response, and trends in immunotherapy were the focus of the Immunotherapy Bridge (November 30th-December 1st, 2022). (biomedcentral.com)
  • There is also a need for rational combinations beyond interleukin (IL)-2 and programmed death (PD)-1/ cytotoxic T-lymphocyte-associated antigen (CTLA)-4 immune checkpoint blockade and to combat exhaustion and restore costimulatory functions, e.g., with gene-engineered or pharmacologic agent-treated TILs. (biomedcentral.com)
  • MSCs represent a lifelong reservoir for the generation of somatic cells and for cell replacement. (encyclopedia.pub)
  • While CTCF is essential for embryonic development, little is known of its absolute requirement in somatic cells and the consequences of CTCF haploinsufficiency. (preprints.org)
  • The occurrence of highly polymorphic mono- and dinucleotide MICROSATELLITE REPEATS in somatic cells. (lookformedical.com)
  • [ 8 ] Preferential accumulation of progerin in vascular endothelial and smooth muscle cells has been observed. (medscape.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)
  • We are also interested in gene targeting methods and in figuring out why these types of gene replacement and modification are quite inefficient, even in yeast. (brandeis.edu)
  • Dr. Cong's group is developing novel genome technology for genome engineering and single-cell genomics, leveraging scalable computational methods. (stanford.edu)
  • Despite this, clinical responses are typically transient as tumour cells develop resistance. (babraham.ac.uk)
  • However, obtaining primary neuronal cells from adult tissue is difficult and faces major ethical issues in clinical practice. (hindawi.com)
  • The majority of glioblastomas are IDH wild-type and correspond to the longstanding clinical description of primary glioblastomas, which arise rapidly from non-neoplastic brain cells and progress quickly. (cancernetwork.com)
  • Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)
  • Previous studies have demonstrated that immortalized astrocytes are not only easily manipulated, reproducible, and nontumorigenic but are also safe potential vehicles for the delivery of therapeutic genes (galanin) for chronic pain therapy [ 7 - 9 ]. (hindawi.com)
  • Studies have increasingly focused on the potential therapeutic effects of stem cell transplantation for neurological diseases [ 10 ]. (hindawi.com)
  • HER2/neu (also called ERB B2 ) is the gene that encodes the human epidermal growth factor receptor type 2. (cancerquest.org)
  • When the RAD50 gene is functioning properly, the MRN complex helps to detect and repair double-strand DNA breaks, which can occur naturally during cell replication or due to external factors such as radiation or exposure to certain chemicals. (tangut.net)
  • DNA damage caused by these genotoxins can be efficiently fixed by DNA repair in cooperation with cell cycle checkpoints. (biomedcentral.com)
  • We have focused a lot of attention on yeast mating-type gene switching ( MAT switching) as an example of DSB repair that we can study in great detail. (brandeis.edu)
  • MAT switching is an example of a repair process called gene conversion. (brandeis.edu)
  • Mesenchymal stem/stromal cells (MSCs) are a reservoir for tissue homeostasis and repair that age during organismal aging. (encyclopedia.pub)
  • 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)
  • 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)