• 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)
  • Thus, in order to avoid excessive ROS generation, they switch the utilization of metabolic pathways that require mitochondrial respiration to fermentation [ 3 ]. (hindawi.com)
  • 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 encoded protein may also be involved in regulating the O6-methylguanine-induced apoptosis signaling pathway. (nih.gov)
  • These activate the ""late"" transcriptional reprogramming influencing DNA repair, cell cycle regulation and apoptosis. (europa.eu)
  • These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug. (hindawi.com)
  • Cells are also programmed for death at the genetic level as a response to DNA damages through the process of apoptosis. (bdbiosciences.com)
  • 2 Apoptosis is triggered by caspase-mediated signal transduction pathways. (bdbiosciences.com)
  • As cells become damaged or are no longer needed, they undergo apoptosis or programmed cell death, a normal physiological process that occurs during embryonic development and tissue homeostasis. (bdbiosciences.com)
  • Apoptosis controls the orderly death of damaged cells, whereas necrosis occurs as a result of tissue damage, causing the loss of both damaged and surrounding cells. (bdbiosciences.com)
  • 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)
  • Here, we aim to provide an overview on the mechanisms of miRNA biogenesis and to discuss the functional impact of miRNAs on PCa under radiation response. (frontiersin.org)
  • 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)
  • 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)
  • 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)
  • Beyond Red Hair and Sunburns: Uncovering the Molecular Mechanisms of MC1R Signaling and Repair of UV-Induced DNA Damage. (uc.edu)
  • We aim to understand the molecular mechanisms that allow plants to integrate beneficial and damaging effects of light and respond to them with striking plasticity. (csic.es)
  • His insights into the basic mechanisms of the DNA damage response have profoundly enriched our understanding not only of the fundamental genetics of all cellular life, but also of how we conceptualize many diseases and conditions, especially cancer. (harvard.edu)
  • He then moved to the Tokyo Institute of Technology in Japan as a postdoctoral researcher to investigate the mechanisms of recombinational DNA repair through biochemical and genetic approaches (2016-2021). (imperial.ac.uk)
  • Human bone marrow CD34(+) hematopoietic progenitor cells (HPC) were exposed in vitro to 1,4-BQ to assess cytotoxicity, genotoxicity, and DNA damage responses and the molecular mechanisms associated with these events. (rti.org)
  • Radiotherapy was delivered to ipsilateral axil- cancer patients in the future, it is essential to increase our lary and supraclavicular lymph nodes and the remaining knowledge in mechanisms responsible for drug resistance, breast parenchyma after breast conservation surgery or tho- and to define reliable indicators for response to therapy. (lu.se)
  • Although highly preliminary, the findings suggest that different tumor biological factors may predict response to different chemotherapy regimens with distinct mechanisms of action. (lu.se)
  • 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)
  • Next, we discuss the mechanisms and possible exposures leading to DNA damage and p53 hyperactivation culminating in microcephaly. (bvsalud.org)
  • 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)
  • Daphne Haas-Kogan, MD , is studying signaling pathways commonly activated in gliomas and pediatric malignancies and inhibitors that target elements within these pathways. (dana-farber.org)
  • Alan D'Andrea, MD , is studying the molecular signaling pathways that regulate the DNA damage response in mammalian cells. (dana-farber.org)
  • Endothelin-1 Protects Human Melanocytes from UV-Induced DNA Damage by Activating JNK and p38 Signaling Pathways. (uc.edu)
  • The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. (hindawi.com)
  • Eukaryotic cells respond to DNA damage by activating signaling pathways that promote cell cycle arrest and DNA repair. (kegg.jp)
  • While most molecular biologists thought signaling pathways worked by sensing signals extrinsic to the cell and relaying the information to the nucleus, Elledge was proposing an internal signaling pathway that senses cell-intrinsic events. (the-scientist.com)
  • Pathway redundancy is complex and rarely studied alongside mitochondrial dysfunction or ROS both of which influence chemoresistance. (ncri.org.uk)
  • DDR abrogation patterns permitted construction of DDR signatures which classify explant platinum cytotoxicity, mitochondrial membrane dysregulation, and ROS response (AUCs:1). (ncri.org.uk)
  • 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)
  • He noted that the authors identified several proteins as facilitating the neurodegeneration that is wrought by damaged mitochondrial DNA. (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)
  • Our study additionally shows that the majority of AT heterozygotes express almost halved levels of ATM protein, sufficient in most cases to normally regulate the ATM-dependent DNA damage-response pathway. (nih.gov)
  • The overall goal of my laboratory is to understand the signals that regulate the p53 pathway and the consequences of expressing wild-type or mutant p53. (mdanderson.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)
  • Reactive oxygen species (ROS), generated as consequence of oxidative metabolism, activate signal transduction pathways, which contribute to cellular homeostasis [ 1 ]. (hindawi.com)
  • In particular, we will discuss the modifications in intrinsic and extrinsic apoptotic pathways caused by proteins encoded by HPV early genes. (mdpi.com)
  • Oxidative stress produces DNA damage and also induces responses, which could help the cell to restore the initial equilibrium. (hindawi.com)
  • Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. (cdc.gov)
  • 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)
  • 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)
  • 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)
  • 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)
  • This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers. (cdc.gov)
  • The mechanistic basis of DDR has been classically thought to consist of an ""early"" post-translational response, which results in activation of several signalling pathways and transciption factors. (europa.eu)
  • 2012) . Sterile inflammation associat- The key mechanistic pathways and vation of inflammatory cel s (Balkwill, ed with inhalation of crystal ine silica mediators involved in inflamma- 2012 ). (who.int)
  • Mutations in the positively charged residues completely abrogate DNA binding and subsequent interferon production through STING. (wikipedia.org)
  • In vitro behavior and UV response of melanocytes derived from carriers of CDKN2A mutations and MC1R variants. (uc.edu)
  • When individuals are born with mutations in this pathway, they often have severe developmental defects. (harvard.edu)
  • 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)
  • He found that RNR2 RNA levels increased dramatically, even more than the protein levels, upon exposure of cells to DNA damage and that mutations in RNR2 resulted in hypersensitivity to DNA damage. (the-scientist.com)
  • 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)
  • Although epigenetically silenced, endogenous retroviral (ERV) genes become activated in tumors and function to ignite immune responses. (frontiersin.org)
  • Interestingly, tumors with both negative mdm-2 and p21 expression, irrespective of p53 status, had a high response rate to docetaxel but no response to MF. (lu.se)
  • 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)
  • Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. (cdc.gov)
  • Elledge and Witkin are being honored for their seminal discoveries that have illuminated the DNA damage response, a cellular pathway that senses when DNA is altered and sets in a motion a series of responses to protect the cell. (harvard.edu)
  • That is because each time a cell makes a copy of itself, DNA is vulnerable to damage, not only from faulty cellular processes, but also from such entities as environmental chemicals. (harvard.edu)
  • Although interindividual variations were evident in the cellular response to 1,4-BQ, there was no gender difference in the response overall. (rti.org)
  • Upon recognition of a PAMP, PRRs generate signal cascades leading to transcription 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)
  • DNA was cool itself, but the fact that you could take it apart and put it back together and test ideas on genes-that totally blew my mind. (the-scientist.com)
  • However, there were no significant changes in mRNA levels of the DNA repair genes ku80, rad51, xpa, xpc, and ape1 as well as p53 following treatment with 1,4-BQ. (rti.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)
  • However, recent data suggest that TTFields may also attenuate DNA damage repair and replication fork dynamics, providing a potential platform for therapeutic combinations incorporating standard-of-care treatments and targeted DNA damage response inhibitors (DDRi). (nature.com)
  • Mitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. (kegg.jp)
  • Elledge's idea that eukaryotic cells sense the progress of DNA replication and transform that information into a DNA-damage response was new. (the-scientist.com)
  • Those results led him to study how cells monitor roadblocks to replication and DNA damage, such as nicks and double-stranded breaks, and how the cell handles that information. (the-scientist.com)
  • Slow-clearing parasites also exhibited decreased expression of proteins involved in DNA replication and decelerated development at the young ring stage. (cdc.gov)
  • The protein is likely to be involved in the response to DNA damage during replication, as well as in the replication and transcription processes. (medscape.com)
  • WS have been classified is a member of the RecQ family of DNA helicases implicated in the resolution of DNA structures leading to the stall of replication forks. (medscape.com)
  • DNA is normally found in the nucleus of the cell. (wikipedia.org)
  • In normal cells, DNA is confined to the nucleus or mitochondria. (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)
  • cGAS is also found in the nucleus where tight tethering to chromatin prevents its activation by self-DNA. (wikipedia.org)
  • In the nucleus it behaves as a DNA chaperone, sustains nucleosome dynamics and chromosomal stability, and contributes to telomere maintenance [ 10 ]. (hindawi.com)
  • These include changes in the plasma membrane (such as loss of membrane symmetry and loss of membrane attachment), a condensation of the cytoplasm and nucleus, protein cleavage, and internucleosomal cleavage of DNA. (bdbiosciences.com)
  • We aim to understand how plants respond to beneficial and damaging light stimulus by controlling in a coordinated way protein homeostasis, chromatin dynamics and transcriptional networks. (csic.es)
  • DET1 was identified in light-related screenings, is related to DNA damage responses and binds chromatin. (csic.es)
  • 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)
  • ATF-3 induces DNA synthesis and expression of cyclin D1 in hepatocytes [ 21 ] and is involved in serum-induced cell proliferation as a target gene of c-myc [ 10 ]. (hindawi.com)
  • High tumor proliferation has previously been associated with response to chemotherapy. (lu.se)
  • DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway. (invivogen.com)
  • However, it remains unexplored if TIGAR plays an important role in DNA damage and repair. (nature.com)
  • Here, we present our findings on a novel role of TIGAR in DNA damage and repair. (nature.com)
  • We show that TTFields robustly activates PARP- and ATR-mediated DNA repair (including PARylation and CHK1 phosphorylation, respectively), whilst combining TTFields with PARP1 or ATR inhibitor treatment leads to significantly reduced clonogenic survival. (nature.com)
  • Dipanjan Chowdhury, PhD , is studying two aspects of the DNA damage response: the dephosphorylation of DNA repair proteins via phosphatases, and the decreased expression of repair factors via microRNAs (miRNAs). (dana-farber.org)
  • Kent Mouw, MD, PhD , is using a combination of genomic and functional approaches to study the role of DNA repair pathway alterations in tumor behavior and treatment response. (dana-farber.org)
  • Along with collaborators, Mouw is working to identify DNA repair biomarkers to guide the use of chemotherapy, radiation, and targeted agents. (dana-farber.org)
  • MC1R: Front and Center in the Bright Side of Dark Eumelanin and DNA Repair. (uc.edu)
  • The ATM protein coordinates DNA repair by activating enzymes that fix the broken strands. (medlineplus.gov)
  • Efficient repair of damaged DNA strands helps maintain the stability of the cell's genetic information. (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)
  • The p53 protein is activated in response to DNA damage, serving as a checkpoint in the elimination or repair of cells with damaged DNA. (mdanderson.org)
  • As a start to designing those gene-targeting tools, Elledge, now a professor of genetics at Harvard Medical School, began by trying to clone the mammalian homolog of recA , a bacterial gene required for DNA repair via recombination. (the-scientist.com)
  • Bilge is an MSCA research fellow investigating recombinational DNA repair. (imperial.ac.uk)
  • Different repair pathways are implicated in the resolution of such lesions. (bvsalud.org)
  • This review explains mammalian cortical development and the major DNA repair pathways that may lead to microcephaly when impaired. (bvsalud.org)
  • Several pathways involved in cell cycle and DNA repair were affected upon NV651 treatment. (lu.se)
  • However, defects in these pathways are often associated with neurological disorders, indicating the pivotal role of DDR in normal brain development. (bvsalud.org)
  • In addition, this work implicates alterations in immune signaling and drugs in development to target inflammatory responses may also bring ancillary benefit," Beck said. (medscape.com)
  • Alterations in components of the p53 pathway, such as amplification of the Mdm2 gene, which encodes a p53 inhibitor, also contribute to tumorigenesis. (mdanderson.org)
  • WP1130 (Degrasyn) is a novel selective small molecular deubiquitinase inhibitor and a Bcr/Abl destruction pathway activator that specifically and rapidly down-regulates both wild-type and mutant Bcr/Abl protein without affecting bcr/abl gene expression in chronic myelogenous leukemia (CML) cells. (adooq.com)
  • A study published this last week in the Journal of Cell Biology reports that researchers have uncovered a molecular pathway that contributes to triple-negative breast cancer, a deadly and treatment resistant form of cancer that often occurs in young women. (vitamindcouncil.org)
  • And more yet, vitamin D might be involved in this molecular pathway. (vitamindcouncil.org)
  • A molecular pathway is a series of actions among molecules in a cell that lead to a change in that cell. (vitamindcouncil.org)
  • This study investigated the role of TIGAR in DNA damage response (DDR) induced by genotoxic drugs and hypoxia in tumor cells. (nature.com)
  • 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)
  • The researchers found that activation of the discovered pathway allows tumor cells to continue growing unchecked. (vitamindcouncil.org)
  • p53, mdm-2, p21, and mib-1 expression were not significantly associated with response to chemotherapy, time to progression, or overall survival in the whole patient population or in the docetaxel group. (lu.se)
  • The results of our phenotype analysis also indicate that it is more likely that a panel of tumor biological factors instead of only one single factor may be needed for better prediction of chemotherapy response. (lu.se)
  • 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)
  • HRD cells had increased SSB pathway abrogation vs NHEJ-defective cells. (ncri.org.uk)
  • 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)
  • Loss of FLCN-FNIP1/2 induces a non-canonical interferon response in human renal tubular epithelial cells. (nih.gov)
  • We characterized the ATM protein expression in immortalized cells from AT and AT-variant patients, and heterozygotes and correlated it with two ATM-dependent radiation responses, G1 checkpoint arrest and p53-Ser 15 phosphorylation. (nih.gov)
  • 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)
  • Here, we review some of the recent advances and studies that highlight the roles of these changes as well as antigen presentation and stress response pathways in beta cells in the onset and propagation of the autoimmune process in type 1 diabetes. (springer.com)
  • We advance the hypothesis that antigen presentation by beta cells, their stress responses and functional heterogeneity are critical factors that will provide clues towards solving the enigma posed by islet autoimmunity in type 1 diabetes. (springer.com)
  • When conditions are right, cells enter the S stage of the cell cycle and commit to DNA synthesis and replicate their chromosomal DNA. (bdbiosciences.com)
  • In the final stages of the process, dying cells become fragmented into apoptotic bodies and consequently are eliminated by phagocytic cells without significant inflammatory damage to surrounding cells. (bdbiosciences.com)
  • His first experimental results contained a serendipitous artifact that laid the foundation for a scientific career studying how eukaryotic cells deal with damage to their DNA. (the-scientist.com)
  • Elledge had found that Rnr2 protein levels increased when yeast cells were grown in the presence of agents that damaged DNA. (the-scientist.com)
  • The Loring lab will develop a new technique for quickly and easily detecting DNA damage in stem cells. (scripps.edu)
  • Bone marrow stem cells are targets for benzene-induced cytotoxicity and DNA damage that could result in changes to the genome of these progenitor cells, thereby leading to hematopoietic disorders and cancers. (rti.org)
  • In addition, the p21 mRNA level was elevated in 1,4-BQ-treated cells, suggesting that human CD34(+) cells utilize the p53 pathway in response to 1,4-BQ-induced DNA damage. (rti.org)
  • These results show that human CD34(+) cells are sensitive targets for 1,4-BQ toxicity that use the p53 DNA damage response pathway in response to genotoxic stress. (rti.org)
  • Cytotoxic drugs damage DNA and kill many normal cells as well as cancer cells. (msdmanuals.com)
  • In contrast, other drugs (eg, DNA cross-linkers, also known as alkylating agents) have a linear dose-response relationship, killing more cancer cells at higher doses. (msdmanuals.com)
  • Skin fibroblasts in WS patients demonstrate characteristics of cells in conditions of stress with slow growth rates, an elongated cell cycle, and an altered morphology that suggests stress-induced premature senescence transduced in part by the p38α MAP kinase signaling pathway. (medscape.com)
  • The cGAS - STING pathway acts to detect cytosolic DNA and induce an immune response. (wikipedia.org)
  • Studying RNR2' s regulatory elements, he found those that were necessary to induce the production of higher protein levels in response to DNA damage and identified factors that bind these DNA elements to mediate the response of RNR2 to DNA damage. (the-scientist.com)
  • Cyclin-CDK inhibitors (CKIs), such as p16Ink4a, p15Ink4b, p27Kip1, and p21Cip1, are involved in the negative regulation of CDK activities, thus providing a pathway through which the cell cycle is negatively regulated. (kegg.jp)
  • 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)
  • Together, the data support a possible thiol mediated transcarbamoylating mechanism linking MDI exposure to pathogenic eosinophilic inflammatory responses. (cdc.gov)
  • However, this limited expression of ATM protein provides no benefit regarding the ATM-dependent responses related to G1 arrest and p53-ser15 phosphorylation. (nih.gov)
  • GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. (hindawi.com)
  • In response to DNA-damaging agents, the wild-type p53-activated fragment 1 (WAF1 also known as p21) is an important downstream effector in the p53-specific growth arrest pathway. (lu.se)
  • This pathway plays a critical role in mediating immune defense against double-stranded DNA viruses. (wikipedia.org)
  • Because all pathogens utilize nucleic acid to propagate, DNA and RNA can be recognized by PRRs to trigger immune activation. (wikipedia.org)
  • By contrast, photoallergic reactions are cell-mediated immune responses to a light-activated compound. (medscape.com)
  • We found significantly increased severity of congenital Zika syndrome (CZS) in fetuses of DENV-immune cynomolgus macaques infected with ZIKV in early pregnancy compared with naïve controls, which occurred despite no effect on maternal ZIKV infection or antibody responses. (bvsalud.org)
  • The potency of each of these strategies is further enhanced by radiation treatment, leading to increased amounts of DNA damage with profound delay in DNA damage resolution. (nature.com)
  • Brendan Price, PhD , has made major advances in understanding the role of the ataxia-telangiectasia gene product (ATM) as a sensor of DNA damage and a regulator of radiation resistance in the irradiated cell. (dana-farber.org)
  • My research is focused on investigating the function of the melanocortin 1 receptor (MC1R) , its agonists α-melanocyte stimulating hormone (α-MSH) and ACTH, and antagonists agouti signaling protein and human β-defensin 3 in regulating cutaneous pigmentation and the response to UV radiation. (uc.edu)
  • DNA can be damaged by agents such as toxic chemicals or radiation. (medlineplus.gov)
  • Witkin discovered how bacteria respond to DNA damage, detailing the response to UV radiation. (harvard.edu)
  • In response to DNA damage, the checkpoint kinase ATM phosphorylates and activates Chk2, which in turn directly phosphorylates and activates p53 tumor suppressor protein. (kegg.jp)
  • In the current study, using postmortem brain tissue samples from patients with sporadic PD, they confirmed that that there were deletions of mtDNA in the medial frontal gyrus, a region implicated in cognitive impairments in PD, suggesting a potential role of damaged mtDNA in disease pathophysiology. (medscape.com)
  • 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)
  • High-grade gliomas are primary brain cancers with unacceptably low and persistent survival rates of 10-16 months for WHO grade 4 gliomas over the last 40 years, despite surgical resection and DNA-damaging chemo-radiotherapy. (nature.com)
  • Her laboratory attempts to promote progress not only in defining the genomic landscape of human gliomas and pediatric cancers, but also in sensible implementation of targeted therapeutics to maximally impact signaling response. (dana-farber.org)
  • Phototoxic reactions occur because of the damaging effects of light-activated compounds on cell membranes and, in some instances, DNA. (medscape.com)
  • However, for an immediate and effective response, global post-transcriptional control of mRNA stability, splicing and translation may be crucial during "immediate-to-early" DDR. (europa.eu)
  • Upon binding DNA, the protein cyclic GMP-AMP Synthase (cGAS) triggers reaction of GTP and ATP to form cyclic GMP-AMP (cGAMP). (wikipedia.org)
  • One way cytosolic DNA is sensed is via the cGAS/STING pathway, specifically by the cyclic-GMP-AMP synthase (cGAS). (wikipedia.org)
  • The DDR comprises single-strand break (SSB) (BER, NER, MMR) and double-strand break (DSB) (HR, NHEJ) pathways. (ncri.org.uk)
  • An impaired DNA damage response (DDR) permits genomic aberration accrual and is a major chemosensitivity determinant. (ncri.org.uk)
  • 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)
  • During the synthesis (S) phase of the cell cycle, DNA polymerases incorporate a variety of nucleosides (deoxyadenosine, deoxyguanosine, deoxycytidine and thymidine) into the newly extending strands of DNA. (bdbiosciences.com)
  • Antimetabolites such as fluorouracil and methotrexate are cell cycle-specific and have a nonlinear dose-response relationship. (msdmanuals.com)
  • For discoveries that have illuminated the DNA damage response, Stephen J. Elledge, the Gregor Mendel Professor of Genetics and of Medicine at Harvard Medical School and Brigham and Women's Hospital, is being recognized with the Lasker Award. (harvard.edu)
  • Elledge uncovered a DNA-damage-response pathway that operates in more complex organisms, including humans. (harvard.edu)
  • Over the years, Elledge and his colleagues elucidated a signaling network that informs a cell when DNA sustains an injury. (harvard.edu)
  • Then I thought, there must be a sensory pathway that recognizes the DNA damage that's going on in the cell," says Elledge. (the-scientist.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)
  • or =10%) predicted a better response (P = 0.014 and P = 0.046, respectively) to treatment and a longer time to progression in both univariate and multivariate analyses. (lu.se)
  • Breaks in DNA strands also occur naturally when chromosomes exchange genetic material during cell division. (medlineplus.gov)
  • Metal exposures induced ROS, including hydroxyl radical (*OH), resulting in DNA strand breaks and lipid peroxidation. (cdc.gov)
  • 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)
  • 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, is widely used to measure de novo DNA synthesis. (bdbiosciences.com)
  • The proposed project aims to identify the dynamics of RNA-protein interactions during DNA damage response (DDR) using high-throughput "omics" approaches. (europa.eu)