• Proliferative control in cancer cells is frequently disrupted by mutations in the retinoblastoma protein (RB) pathway. (bepress.com)
  • Intriguingly, RB1 mutations can arise late in tumorigenesis in cancer cells whose RB pathway is already compromised by another mutation. (bepress.com)
  • In this study, we present evidence for increased DNA damage and instability in cancer cells with RB pathway defects when RB1 mutations are induced. (bepress.com)
  • DNA alkylating is the transfer of alkyl groups to particular bases, resulting in alkylation products such as O2‐alkylthymine and O6‐methylguanine that lead to DNA mutations. (apexbt.com)
  • These are considered the most severe type of DNA damage, capable of causing genetic mutations or cell death. (globalhealthnewswire.com)
  • On the other hand, DNA repaired by polymerase theta-mediated end-joining (TMEJ) can result in the loss of some genetic information and cause mutations. (globalhealthnewswire.com)
  • After the long-range resection, the damaged DNA is repaired through error-free HR. Furthermore, it was discovered that the binding of MSH2-MSH3 inhibits the access of POLθ, which mediates a more error-prone TMEJ pathway, thereby preventing mutations that may occur during DSB repair. (globalhealthnewswire.com)
  • Cells are regularly exposed to mutagens-factors in the environment which can damage DNA and generate mutations. (jove.com)
  • If these errors are not fixed, the damage can cause mutations which in turn can result in cancer or disease depending on which sequences are disrupted. (jove.com)
  • In humans, mutations in the NER pathway can cause diseases such as xeroderma pigmentosum (XP), which is associated with a 2000-fold increase in the incidence of skin cancer. (jove.com)
  • Mutations in the positively charged residues completely abrogate DNA binding and subsequent interferon production through STING. (wikipedia.org)
  • However, large scale free radical formation may lead to DNA damage and genetic mutations. (american.edu)
  • Genome-caretaking mechanisms counteract the deleterious effects of DNA damage and are essential to prevent toxicity, mutations, genome instability, ageing and disease. (lumc.nl)
  • UV-Induced DNA Damage, Repair, Mutations and Oncogenic Pathways in Skin Cancer. (acs.org)
  • After oxidative stress, one of the main base lesions formed in DNA is 8-oxoguanine (8-oxoG) that, if left unrepaired, induces mutations potentially involved in cancer and aging. (cea.fr)
  • They showed that lack of neuronal IFNβ signaling leads to oxidative damage and mutations in mtDNA in neurons, which are subsequently released outside the neurons. (medscape.com)
  • Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. (lu.se)
  • Under genotoxic stress conditions, the DNA damage response (DDR) machinery is crucial in repairing lesions and preventing mutations in the basic structure of the DNA. (bvsalud.org)
  • Microcephaly is mainly caused by genetic mutations, especially genes encoding proteins involved in centrosomes and DNA repair pathways. (bvsalud.org)
  • Epirubicin was reported to block DNA replication either through direct DNA damage or indirectly through inhibition of replication proteins such as topoisomerase. (nature.com)
  • For instance, DSBs are repaired by DSB repair proteins, while improperly paired DNA bases are repaired by mismatch repair proteins. (globalhealthnewswire.com)
  • However, this study revealed that repair proteins previously thought to be responsible for different repair mechanisms can interact with each other to recognize damaged sites and select an appropriate repair mechanism. (globalhealthnewswire.com)
  • Director Myung said, "This research has revealed a new function of the mismatch repair protein MSH2-MSH3 in regulating DSB repair," adding, "The repair proteins that have been believed so far to act independently in the mismatch repair, double-stranded break repair, and TMEJ repair pathways are now shown to closely interact each other for proper maintenance of genomic integrity. (globalhealthnewswire.com)
  • The process begins when an enzyme complex, shown here in E. coli, containing the proteins UvrA and UvrB, travels along the DNA and detects the physical aberration of the lesion. (jove.com)
  • NER employs a set of specialized proteins that first scan DNA to detect a damaged region. (jove.com)
  • Next, NER proteins separate the strands and excise the damaged area. (jove.com)
  • The first two proteins work together as a complex, traveling along the DNA strands to detect any physical aberrations. (jove.com)
  • In prokaryotes, the NER complex consists of the three Uvr proteins, but in eukaryotes, more than a dozen proteins operate to regulate DNA repair. (jove.com)
  • Cellular signaling pathways are networks of genes, proteins, enzymes, cytokines, and other cellular species that "communicate" in order to govern the basic functions of cells. (american.edu)
  • Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. (mdpi.com)
  • These effects on cellular proteins and pathways were unique to K+CS treatment and were not observed with KPT-330 or CS single agent treatment. (confex.com)
  • Reconstitution of DNA Base Excision-Repair with Purified Human Proteins: Interaction between DNA Polymerase Beta and the XRCC1 Protein," The EMBO Journal, Vol. 15, No. 23, 1996, pp. 6662-6670. (scirp.org)
  • Cells depend on their DNA for coding information to make various classes of proteins that include enzymes, certain hormones, transport proteins, and structural proteins that support life. (cdc.gov)
  • After analysing for many years the way that DNA glycosylases, APE1 and XRCC1 initiate the repair of 8-oxoG or abasic sites, our laboratory is now interested in studying the effect on BER proteins of cellular environmental changes such as oxidative stress or the switch from stem cells to differentiation. (cea.fr)
  • Three hours after the treatment, BER proteins become insoluble and associate to those regions in which DNA (stained with DAPI, blue) is less condensed, corresponding to euchromatin regions. (cea.fr)
  • He noted that the authors identified several proteins as facilitating the neurodegeneration that is wrought by damaged mitochondrial DNA. (medscape.com)
  • Slow-clearing parasites also exhibited decreased expression of proteins involved in DNA replication and decelerated development at the young ring stage. (cdc.gov)
  • Pathway redundancy is complex and rarely studied alongside mitochondrial dysfunction or ROS both of which influence chemoresistance. (ncri.org.uk)
  • Thus, in order to avoid excessive ROS generation, they switch the utilization of metabolic pathways that require mitochondrial respiration to fermentation [ 3 ]. (hindawi.com)
  • Oxidative damage to mitochondrial DNA has been implicated in human degenerative diseases, tumorigenesis and aging. (cea.fr)
  • Damaged mitochondrial DNA (mtDNA) initiates and spreads Parkinson's disease (PD) pathology, potentially opening new avenues for early diagnosis, disease monitoring, and drug development. (medscape.com)
  • Looking ahead, they plan to investigate how mtDNA damage can serve as a predictive marker for different disease stages and progression and to explore potential therapeutic strategies aimed at restoring normal mitochondrial function to rectify the mitochondrial dysfunctions implicated in PD. (medscape.com)
  • However, he said that "while very interesting findings, this is really the first effort that demonstrates how damaged mitochondrial DNA may contribute to neurodegeneration in the context of PD and PD dementia. (medscape.com)
  • We could confirm the increased polyploidy upon Mps1 inhibition in neuroblastoma cell lines and PDX model, leading to mitotic catastrophe activating the caspase-dependent mitochondrial apoptotic pathway. (lu.se)
  • The cGAS-STING pathway is a component of the innate immune system that functions to detect the presence of cytosolic DNA and, in response, trigger expression of inflammatory genes that can lead to senescence or to the activation of defense mechanisms. (wikipedia.org)
  • The presence of DNA in the cytosol is indicative of cellular damage or infection and leads to activation of genes associated with the immune response. (wikipedia.org)
  • Instead of activating DNA repair, the altered ATM protein allows variants to accumulate in other genes, which may cause cells to grow and divide in an uncontrolled way. (medlineplus.gov)
  • In addition, functional assays are being used and developed to assess pathogenicity of DNA variants in cancer-associated genes, and/or to predict outcomes of treatment. (lumc.nl)
  • A. Sorour, I. Talaat, T. Youssif and M. Atta, "Detection of Polymorphisms of DNA Repair Genes (XRCC1 and XPC) in Prostate Cancer," Journal of Cancer Therapy , Vol. 4 No. 10, 2013, pp. 1499-1505. (scirp.org)
  • The total chromosomal content of a cell involves approximately 105 genes in a specialized macromolecule of deoxyribonucleic acid (DNA). (cdc.gov)
  • But some melanoma cells appear to rely heavily on the NHEJ pathway to produce extra copies of genes that may be responsible for drug resistance, according to results published in Cancer Discovery on January 26. (cancer.gov)
  • In addition, these alterations affect 3 principal categories of genes, as follows: proto-oncogenes, tumor suppressor genes, and DNA repair genes. (medscape.com)
  • Therefore, inhibition of DNA repair pathways to which CLL cells with loss of ATM signalling become addicted could provide 'synthetic lethality' and induce tumour specific killing. (birmingham.ac.uk)
  • Here we expand the concept of synthetic lethality in ATM-null CLL and address the question of whether ATM-null deficient CLL cells can be targeted by inhibition of the ATR protein that governs responses to post-replicative damage and co-operates with ATM. (birmingham.ac.uk)
  • We further show that inhibition of a single DDR process (FA pathway, PARP, ATR or ATM) increases the susceptibility of glioblastoma cell lines and patient-derived GSCs to current adjuvant therapy. (whiterose.ac.uk)
  • In clinically-relevant 3D GSC models, simultaneous inhibition of the FA pathway (FAPi) and PARP or ATR enhanced temozolomide sensitisation compared to a single DDR inhibitor (DDRi). (whiterose.ac.uk)
  • Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. (mdpi.com)
  • This study investigated the role of TIGAR in DNA damage response (DDR) induced by genotoxic drugs and hypoxia in tumor cells. (nature.com)
  • To define a role of TIGAR in DNA damage, TIGAR expression was knocked down with siRNA in HepG2 cells. (nature.com)
  • Epirubicin, a DNA damaging anticancer agent and CoCl 2 , which was used to imitate hypoxia condition, was applied to induce DNA damage in TIGAR knockdown HepG2 cells. (nature.com)
  • DNA damage in HepG2 cells after TIGAR knockdown with or without treatment of epirubicin or CoCl 2 was detected by Comet assay. (nature.com)
  • Cells with even one mutant copy of RB1 have increased basal levels of DNA damage and increased mitotic errors. (bepress.com)
  • RB1 deletion in retinoblastoma protein pathway-disrupted cells results in DNA damage and cancer progression" Molecular and Cellular Biology Vol. 39 Iss. (bepress.com)
  • The samples also differed in the basal activity of the hypoxia pathway: the highest level was detected in TP53-mutant samples, followed by profile II and profile I. Our study suggests that wild-type TP53 CLL cells with less phosphorylated p53 show TP53-mutant-like behavior after DNA damage. (muni.cz)
  • HSER in normal and XP-C cell lines, but not CS-A, XP-A, XP-D or XP-G cells, suggests that HS treatment can enhance the repair of UV-damaged DNA through an enhancement of transcription coupled repair (TCR) or a mechanism which involves the TCR pathway. (mcmaster.ca)
  • Cells maintain genome integrity by having various pathways to repair DSBs. (globalhealthnewswire.com)
  • Laser microirradiation is used to mimic the DSBs in cells and measure the recruitment of green flurecent protein-labeled MSH2 (GFP-MSH2) or EXO1 (GFP-EXO1) to the DNA damage site (indicated by the red line) under a confocal microscope. (globalhealthnewswire.com)
  • There are various repair mechanisms in our cells, each tailored to the type of DNA damage. (globalhealthnewswire.com)
  • The hypothesis proposed by the researchers is that by inhibiting the function of PRKDC, DNA damage is worsened within tumor cells, and a synergistic effect takes place where the effect of doxorubicin is amplified, thereby killing the tumor. (uwinhealth.com)
  • In normal cells, DNA is confined to the nucleus or mitochondria. (wikipedia.org)
  • ATM-null cells are defective in a type of DSB repair that involves homologous recombination and rely on co-operating and compensatory DNA repair pathways for their survival. (birmingham.ac.uk)
  • Additionally, the ATM protein assists cells in recognizing damaged or broken DNA strands. (medlineplus.gov)
  • Cells without any functional ATM protein are hypersensitive to radiation and do not respond normally to DNA damage. (medlineplus.gov)
  • These include novel resected and residual disease models based on careful macrodissection of rare en-bloc partial lobectomy specimens to liberate parallel GSC lines from the tumour core and adjacent infiltrated brain, which represent cells removed and those typically left behind after surgery. (whiterose.ac.uk)
  • HRD cells had increased SSB pathway abrogation vs NHEJ-defective cells. (ncri.org.uk)
  • Assistant Professor of Mathematics and Statistics Julia Chifman and her collaborators built a predictive mathematical model that connects four key cytosolic cellular signaling pathways in breast epithelial cells: the oncogenic pathway, the oxidative stress response pathway, the iron utilization pathway, and the iron homeostasis pathway. (american.edu)
  • The oncogenic signaling pathway includes cellular species that regulate the growth, differentiation, and survival of cells. (american.edu)
  • One of the treatments applied in cancer is radiotherapy (RT), a therapeutic modality that uses ionizing radiation to induce damage in unwanted cells. (frontiersin.org)
  • The main goal of RT consists in delivering a precise dose of radiation in a target volume, such as tumor, promoting the tumor cells eradication with as minimal damage as possible in surrounding normal tissues ( 13 ). (frontiersin.org)
  • In addition, it can stimulate apoptosis of cells containing damaged DNA. (medscape.com)
  • The Loring lab will develop a new technique for quickly and easily detecting DNA damage in stem cells. (scripps.edu)
  • DNA in most cells is regularly damaged by endogenous and exogenous mutagens. (scirp.org)
  • Glycolysis is an important metabolic pathway that generates energy in various cells of the blood vessel wall. (wjgnet.com)
  • A number of direct and indirect radiation interaction pathways can produce damage to the DNA of irradiated cells. (cdc.gov)
  • ONE of the mechanisms that make damaged cells commit suicide is switched off in the embryo, say researchers. (newscientist.com)
  • In healthy cells, this NHEJ pathway helps repair specific types of damage to DNA. (cancer.gov)
  • Finding treatments for resistant cancers "is a daunting clinical problem," said Dr. Lo, noting that many pathways in cells can lead to drug resistance. (cancer.gov)
  • For instance, the non-homologous DNA end joining and homologous recombination pathways are central cellular mechanisms by which eukaryotic cells maintain genome integrity. (bvsalud.org)
  • The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
  • Disruption of the TP53 pathway is a well-known prerequisite for continued proliferation of cells with massively damaged DNA. (lu.se)
  • This offers one of the most challenging paradoxes in cancer biology: what is required of a cell to not only survive massive genetic damage but also outcompete neighboring cells and present as a malignant tumor? (lu.se)
  • Thus, Julia Chifman's research aims to understand the cause of iron dysregulation in breast cancer through the study of certain cellular signaling pathways that affect iron homeostasis. (american.edu)
  • The mechanisms of radioresistance are still poorly understood, despite it has been suggested that miRNAs play an important role in cell signaling pathways. (frontiersin.org)
  • We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. (mdpi.com)
  • In addition to the pathogonomic translocation , MCL progression is controlled by secondary genetic abberations and dysregulated signaling pathways involved in DNA damage repair , proliferation , and apoptosis . (wikidoc.org)
  • Specifically, it was revealed that MSH2-MSH3, a DNA mismatch repair protein, actually plays a crucial role in the DSB repair process. (globalhealthnewswire.com)
  • Nucleotide excision repair relies on specific protein complexes to recognize damaged regions of DNA and flag them for removal and repair. (jove.com)
  • PRKDC is a protein involved in DNA damage repair. (uwinhealth.com)
  • Upon binding DNA, the protein cyclic GMP-AMP Synthase (cGAS) triggers reaction of GTP and ATP to form cyclic GMP-AMP (cGAMP). (wikipedia.org)
  • identified cGAS as the DNA-sensing protein able to trigger interferon beta by synthesizing the second messenger, 2'3'-cGAMP. (wikipedia.org)
  • Ataxia Telangiectasia Mutated (ATM) protein coordinates responses to DNA double strand breaks (DSBs) and the ATM-null status caused by biallelic ATM gene inactivation in chronic lymphocytic leukemia (CLL) results in resistance to p53-dependent apoptosis. (birmingham.ac.uk)
  • ATM is a serine/threonine protein kinase that synchronises rapid DNA damage response (DDR) to DNA double strand breaks (DSBs) with activation of cell cycle checkpoints, DNA repair and apoptosis via p53 activation. (birmingham.ac.uk)
  • The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. (medlineplus.gov)
  • Because of its central role in cell division and DNA repair, the ATM protein is of great interest in cancer research. (medlineplus.gov)
  • Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. (mdpi.com)
  • Mechanistically, protein profiling through mass spectroscopy revealed that K+CS uniquely affects the cellular pathways of DNA damage repair, DNA synthesis and cell cycle progression. (confex.com)
  • This gene encodes a protein that binds to the tumor suppressor folliculin and to AMP-activated protein kinase (AMPK), and may play a role cellular metabolism and nutrient sensing by regulating the AMPK-mechanistic target of rapamycin signaling pathway. (nih.gov)
  • The encoded protein may also be involved in regulating the O6-methylguanine-induced apoptosis signaling pathway. (nih.gov)
  • Our proteomic analysis of extracellular vesicles containing damaged mtDNA identified the TLR4 activator, ribosomal protein S3, as a key protein involved in recognizing and extruding damaged mtDNA," the investigators write. (medscape.com)
  • these pathways may mitigate protein damage caused by artemisinin. (cdc.gov)
  • The cGAS - STING pathway acts to detect cytosolic DNA and induce an immune response. (wikipedia.org)
  • namely, defects in the oncogenic pathway are noted to induce modifications in cellular iron homeostasis. (american.edu)
  • It specifically negatively regulates the PI3K-AKT signaling pathway to induce cell cycle arrest. (medscape.com)
  • The current study aimed to advance our understanding of tirapazamine-induced lesions and the pathways involved in their repair. (aacrjournals.org)
  • Exposure to mutagens can damage DNA and result in bulky lesions that distort the double-helix structure or impede proper transcription. (jove.com)
  • Thus BER is a major barrier to prevent accumulation of DNA lesions therefore protecting against cell death or mutagenesis. (cea.fr)
  • It is now clear that BER is the main pathway involved in the removal of these lesions. (cea.fr)
  • Different repair pathways are implicated in the resolution of such lesions. (bvsalud.org)
  • Previous study revealed that the protective effect of TIGAR in cell survival is mediated through the increase in PPP (pentose phosphate pathway) flux. (nature.com)
  • They also develop specific strategies to increase ROS resistance, which include deviation of the glycolytic flux into the pentose phosphate pathway (PPP) or changes in other enzymatic mechanisms enhancing ROS detoxification [ 3 , 4 ]. (hindawi.com)
  • p53 hypophosphorylation and the related lower ability to respond to DNA damage are linked to ATM locus defects and the higher basal activity of the hypoxia pathway. (muni.cz)
  • Tumours with defects in DNA damage repair mechanisms may be candidates for immunotherapy and other molecular therapeutics specifically targeting these defects. (lumc.nl)
  • However, defects in these pathways are often associated with neurological disorders, indicating the pivotal role of DDR in normal brain development. (bvsalud.org)
  • The maintenance of the steady-state equilibrium between ROS generation and elimination is crucial for cell survival, while its loss causes cell death by different mechanisms triggered by oxidative damage. (hindawi.com)
  • We are presently trying to understand what mechanisms regulate the targeting of the DNA glycosylases, in particular OGG1, to the mitochondria and how BER is coordinated in this organelle. (cea.fr)
  • Next, we discuss the mechanisms and possible exposures leading to DNA damage and p53 hyperactivation culminating in microcephaly. (bvsalud.org)
  • To identify targetable mechanisms and pathways underlying the initiation and progression of SAID. (lu.se)
  • The mechanisms by which isocyanates cause asthma remain unclear, hampering disease prevention, diagnosis, and treatment.7 It is assumed the reactive nature of N=C=O groups underlies isocyanate asthma, with a hapten-based mechanism as the most obvious pathway to pathogenesis.8 However, the critical "self" reaction targets for isocyanate in vivo remain uncertain. (cdc.gov)
  • Here we show that cell cycle progression through mitosis following double-stranded DNA breaks leads to the formation of micronuclei, which precede activation of inflammatory signalling and are a repository for the pattern-recognition receptor cyclic GMP-AMP synthase (cGAS). (nature.com)
  • Figure 2: Progression through mitosis underlies inflammatory pathway activation. (nature.com)
  • In earlier work, the researchers identified dysregulated interferon-beta (IFNβ) signaling as a "top candidate pathway" associated with sporadic PD and its progression to PD with dementia (PDD). (medscape.com)
  • Some patients may have more than one type of resistant tumor, and in each resistant tumor different pathways may be responsible for the resistance. (cancer.gov)
  • We studied p53 phospho-profiles induced by DNA-damaging agents (fludarabine, doxorubicin) in 71 TP53-intact primary CLL samples. (muni.cz)
  • DNA damage increases TP53 levels through an ATM-dependent pathway. (medscape.com)
  • Such dichotomous kinetics implicate additional rate-limiting steps that are essential for DNA-damage-induced inflammation. (nature.com)
  • To unveil roles of DNA damage and antibody effector pathways in inflammation. (lumc.nl)
  • Localisation of BER complexes into euchromatin regions after induction of oxidative DNA damage. (cea.fr)
  • Indeed, it has been shown that miRNAs play an important role in gene expression, mainly when associated with the monitoring of several cell and metabolic pathways, being also an essential component of the gene silencing machinery in most eukaryotic organisms ( 4 , 8 ). (frontiersin.org)
  • Research using the model pointed toward potential pathways to improve therapies, including DNA damage repair pathways which are well-known for their involvement in other types of cancer. (bioengineer.org)
  • Anomalies within the cellular DNA damage response (DDR) contribute to the treatment refractory nature of this devastating brain tumour with difficult-to-treat glioblastoma stem cell (GSC) subpopulations reported to exhibit heightened activity in various DDR processes. (whiterose.ac.uk)
  • Furthermore, patient-derived GSC populations, which drive therapeutic resistance, display high FA pathway expression relative to paired bulk tumour cell populations. (whiterose.ac.uk)
  • In this report, we have determined that heat induces perturbations in some of the earliest events in the cellular response to DNA damage induced by ionizing radiation. (figshare.com)
  • Oxidative stress produces DNA damage and also induces responses, which could help the cell to restore the initial equilibrium. (hindawi.com)
  • Introduction: Glioblastoma represent around half of newly diagnosed glial tumours and continue to portend poor survival (median 15.6 months) despite maximal safe surgical resection followed by DNA-damaging adjuvant therapies. (whiterose.ac.uk)
  • This thesis therefore, considers whether combined targeting of the FA pathway and interconnected DDR processes could form a basis for new, effective multimodal therapies. (whiterose.ac.uk)
  • The Cdk5-AMT signal pathway involved in regulation of DDR by TIGAR defines a new role of TIGAR in cancer cell survival and it suggests that TIGAR may be a therapeutic target for cancers. (nature.com)
  • Host cell reactivation (HCR) of beta-galactosidase (beta-gal) activity for UV-irradiated Ad5HCMVsp1lacZ was used as an indicator of DNA repair in the transcribed strand of an active gene. (mcmaster.ca)
  • DNA is normally found in the nucleus of the cell. (wikipedia.org)
  • cGAS is found at the plasma membrane and is responsible for detecting cytosolic double stranded DNA, normally found in the cell nucleus, in order to stimulate production of IFN-β. (wikipedia.org)
  • Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. (medlineplus.gov)
  • Furthermore, comparison of a/b ratio enhancement suggests dual-DDRi strategies fundamentally alter the response of GSCs, whilst single cell gel electrophoresis and immunofluorescence studies suggest FA pathway-based DDRi combinations substantially delay the resolution of IR-induced DNA strand breaks at 6 hours post-treatment, with increased persistent DNA double strand breaks at 24 hours. (whiterose.ac.uk)
  • In contrast to PARPi + FAPi, treatment with the ATRi + FAPi combination portended marked generation of RNA:DNA hybrids, however the substantial efficacy of both combinations over single DDRi strategies appeared to be independent of their cell cycle modulatory effects. (whiterose.ac.uk)
  • p53 is a transcription factor whose expression is increased by DNA damage and blocks cell division at the G1 phase of the cell cycle to allow DNA repair. (medscape.com)
  • Radiation can disrupt the structure of the DNA (and other macromolecules), thereby disrupting normal cell and organ functions. (cdc.gov)
  • Our Cell Cycle and DNA Damage Research Guide highlights over 750 products for cell cycle and DNA damage research. (tocris.com)
  • Although most of a eukaryotic cell's DNA is contained in the cell nucleus , the mitochondrion has its own genome ("mitogenome") that is substantially similar to bacterial genomes. (wikipedia.org)
  • Further study revealed that the mechanism through which damaged mtDNA causes pathology in healthy neurons involves dual activation of Toll-like receptor (TLR) 9 and 4 pathways, leading to increased oxidative stress and neuronal cell death, respectively. (medscape.com)
  • Several pathways involved in cell cycle and DNA repair were affected upon NV651 treatment. (lu.se)
  • The combination of NV651 and cisplatin, a DNA damage reagent, resulted in a synergistic effect in cell viability, and a significant increase on cell death in HCC cell lines. (lu.se)
  • The DDR comprises single-strand break (SSB) (BER, NER, MMR) and double-strand break (DSB) (HR, NHEJ) pathways. (ncri.org.uk)
  • These include bends or kinks in the structure which can block DNA replication or transcription. (jove.com)
  • Biochemical fractionation as well as confocal microscopy studies revealed that KBrO3-induced BER foci are completely excluded from heterochromatin rich regions, and are preferentially located in less-condensed DNA areas where active transcription takes place. (cea.fr)
  • The present study provides in vivo evidence that a GSH mediated pathway underlies asthma-like eosinophilic inflammatory responses to respiratory tract isocyanate exposure. (cdc.gov)
  • A recombinant nonreplicating human adenovirus type 5, Ad5HCMVsp1lacZ, expressing the lacZ gene under control of the human cytomegalovirus immediate early promoter, was used to assess the effect of heat-shock (HS) on DNA repair of a UV-damaged reporter gene. (mcmaster.ca)
  • Results: Elevated FA pathway gene expression in gliomas is associated with poor survival. (whiterose.ac.uk)
  • The phosphopentose pathway (PPP), which converts glucose-6-phosphate to ribose-5-phosphate for synthesis of nucleotides and NADPH to reduce DNA damage caused by ROS was reported to be activated in DDR 2 . (nature.com)
  • Another enzyme, DNA polymerase fills the gap with new nucleotides. (jove.com)
  • DNA polymerase fills the gap with new nucleotides, and then the DNA ligase enzyme seals the edges between the new and old DNA. (jove.com)
  • As DNA is a molecule consisting of two strands, either one or both of the strands can be damaged. (globalhealthnewswire.com)
  • Single-strand break (SSB), occur when one of the two strands of DNA is damaged or broken. (globalhealthnewswire.com)
  • On the other hand, a double-strand break (DSB) refers to when both strands of DNA are damaged. (globalhealthnewswire.com)
  • At that location the strands are separated and endonuclease enzymes such as UvrC cleave the strand on both sides of the damage. (jove.com)
  • Once identified, the strands at the damaged location are separated, and endonuclease enzymes such as UvrC cut and excise the affected region. (jove.com)
  • Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information. (medlineplus.gov)
  • A poorly understood feature of these responses is the delayed onset (days), in contrast to the acute DNA-damage responses that occur in minutes to hours. (nature.com)
  • Inhibitors of the FA pathway (FAPi), including novel specific FAPi under development (nFAPi), were validated and assessed alongside other key DDR targets including PARP1, ATR and ATM, and a range of techniques were used to assess FA pathway activity and the effects of combinatorial strategies on DNA damage and responses in GSCs. (whiterose.ac.uk)
  • DNA polymerase and ligase activities are then required to restore the DNA integrity. (cea.fr)
  • One way cytosolic DNA is sensed is via the cGAS/STING pathway, specifically by the cyclic-GMP-AMP synthase (cGAS). (wikipedia.org)
  • Upon directly binding cytosolic DNA, cGAS forms dimers to catalyze production of 2'3'-cGAMP from ATP and GTP. (wikipedia.org)
  • This activity is dependent on cytosolic DNA. (wikipedia.org)
  • To identify biomarkers of susceptibility to DNA damage to improve personalised cancer therapy. (lumc.nl)
  • These are relatively mild damages that can be easily repaired by specialized enzymes that can seal the break and restore the integrity of the DNA molecule. (globalhealthnewswire.com)
  • Mitochondria are stainied with MitoTracker Deep Red (magenta), and the nuclear DNA is visualized by DAPI staining (blue). (cea.fr)
  • Lack of neuronal IFNβ or disruption of its downstream signaling causes the accumulation of damaged mitochondria with excessive oxidative stress and insufficient adenosine triphosphate production. (medscape.com)
  • 44% patients were HRD while partially perturbed and basal competence signatures were evident for remaining pathways. (ncri.org.uk)
  • Whether the elevated TIGAR expression protects DNA damage induced by chemotherapeutic agents or hypoxia has not been explored. (nature.com)
  • Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. (nature.com)
  • DNA can be damaged by various factors such as radical metabolites, radiation, and some toxic chemicals. (globalhealthnewswire.com)
  • UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes to DNA. (jove.com)
  • Our results support the notion that heat-induced perturbations in the earliest events of the cellular response to ionizing radiation-induced DNA damage play a role in heat radiosensitization. (figshare.com)
  • DNA can be damaged by agents such as toxic chemicals or radiation. (medlineplus.gov)
  • Direct macromolecule damage by radiation involves partial or complete energy transfer to one or more electrons on the molecule. (cdc.gov)
  • They also identified mtDNA deletions in a "hotspot" in complex I respiratory chain subunits that were associated with dysregulation of oxidative stress and DNA damage response pathways in cohorts with sporadic PD and PDD. (medscape.com)
  • The base excision repair (BER) pathway is the main pathway for the repair of DNA base damage and single strand breaks. (cea.fr)
  • Direct and indirect ionization of DNA is ultimately responsible for the DNA alterations that adversely affect the structural and genetic integrity of the system. (cdc.gov)
  • HRC-associated chemoresistance is established however emphases on individual pathways are mechanistically insufficient to capture DDR landscapes. (ncri.org.uk)
  • The sixth event, The new medicine of DNA repair pathways: damage repair vulnerabilities in cancer , will take place virtually, hosted by Dr Simon Boulton (The Francis Crick Institute). (ox.ac.uk)
  • The Fanconi anaemia (FA) pathway represents a key DDR process which remains relatively inactive in normal brain, but is re-activated in glioblastoma, raising its value as a foundational target for cancer-specific treatment. (whiterose.ac.uk)
  • Through simulations, Chifman and her collaborators found that overexpression of Ras, a central species in the oncogenic pathway, led to a cancer phenotype in the iron homeostasis pathway. (american.edu)
  • IC à 95 % : 1,4-5,0) était significativement associé à un risque accru de cancer, et ce risque était même supérieur en présence d'un tabagisme paternel important. (who.int)