• Here, we sought to understand the DNA damage response (DDR) to CHK1 inhibition and increase the anti-tumor activity of this pathway. (nih.gov)
  • Next, we determined the subcellular localisation of APE1, which is a DNA repair enzyme in the base excision repair pathway and a transcriptional co-activator. (nottingham.ac.uk)
  • In the long term, the team hopes that a better understanding of the DNA damage pathway may provide clues for cancer treatment in the future. (scienceblog.com)
  • Oxidatively induced DNA damage is mainly repaired by base excision repair pathway with the involvement of a plethora of proteins. (nist.gov)
  • A recently described mechanism promoting cell survival after ionizing radiation (IR)-induced DNA damage involves fragmentation and dispersal of the Golgi apparatus, known as the Golgi-dispersal response (GDR), which uses the Golgi phosphoprotein 3 (GOLPH3)-DNA-dependent protein kinase (DNA-PK)-myosin XVIIIA-F-actin signaling pathway. (psu.edu)
  • Conclusion: The study identifies WASp as a novel effector of the nucleus-to-Golgi cell-survival pathway triggered by IR-induced DNA damage in cells of the hematolymphoid lineage and proposes an impaired GDR as a new cause for development of a "radiosensitive" form of immune dysregulation in patients with WAS. (psu.edu)
  • Here, we delineate a pathway where ATM and ATR kinases phosphorylate a highly conserved region in BRCA2 in response to DSBs. (nature.com)
  • The first, which is called the intrinsic cell death pathway, is evoked by intracellular stresses like radiation, growth factor withdrawal, cytokine deprivation, cytotoxic drugs and is regulated by BCL2 family proteins [ 6 , 7 ]. (hindawi.com)
  • Progression through this pathway leads to the release of cytochrome c from the damaged mitochondrion, which then binds to the adaptor molecule APAF-1 and an inactive "initiator" caspase, procaspase 9, within a multiprotein complex called the apoptosome. (hindawi.com)
  • This pathway is activated by the cell-surface death receptors CD95 (Apo-1 or Fas)/TRAIL/tumor necrosis factor (TNF) receptor 1 family proteins which are located on the plasma membrane, and directly activates the caspase cascade via the recruitment of the "initiator" caspase-8 within a death-inducing signaling complex (DISC) [ 8 ]. (hindawi.com)
  • There are six known systems of DNA repair: pathway of direct reversion of damage, base excision repair (BER), nucleotide-excision repair (NER), mismatch repair (MMR), homologous recombination (HR) and nonhomologous DNA end joining (NHEJ). (springer.com)
  • DNA repair by the nonhomologous end joining (NHEJ) pathway promotes tumor recurrence after chemotherapy and radiotherapy. (dovepress.com)
  • The inactivated p53 protein and the aberrant p53 tumor suppressor pathway plays important roles in the pathogenesis of cervical cancer. (spandidos-publications.com)
  • Mutations in genes that encode proteins of the FA pathway fail to orchestrate the repair of DNA damage caused by DNA interstrand crosslinks. (cancerindex.org)
  • Recently SMC proteins have been shown to aid the daughter cells DNA at the origin of replication to guarantee proper segregation. (wikipedia.org)
  • Unless repaired by DNA repair mechanisms before DNA replication, DNA lesions can lead to genomic instability, which is one of the hallmarks of cancer. (nist.gov)
  • It has been unclear how cells maintain transcription and replication in the presence of increased DNA breaks. (nih.gov)
  • Replication Protein A is the primary eukaryotic ssDNA binding protein that has a central role in initiating the cellular response to DNA damage. (rcsb.org)
  • Genomic integrity is constantly challenged due to the intrinsic susceptibility of DNA to various kinds of damage from exposure to various endogenous (e.g., reactive oxygen species, R-loops, replication stress) and exogenous (radiation, chemical mutagens) factors. (nmt.edu)
  • Notably, we demonstrate that ICLs trigger a checkpoint response independently of origin-initiated DNA replication and uncoupling of DNA polymerase and DNA helicase. (xenbase.org)
  • DNA replication is required To elicit cellular responses to psoralen-induced DNA interstrand cross-links. (xenbase.org)
  • The role of BRCA2 in replication-coupled DNA interstrand cross-link repair in vitro. (xenbase.org)
  • An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. (xenbase.org)
  • Recombinant replication protein A: expression, complex formation, and functional characterization. (xenbase.org)
  • 3) How does the cell protect genome stability in response to DNA replication stress? (mdanderson.org)
  • 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)
  • They found that the biomarkers, which reflect exposure, effect, and potential harm, are both elevated in e-cigarette users compared to the other groups and linked to metal exposure and oxidative DNA damage. (universityofcalifornia.edu)
  • Our study found e-cigarette users are exposed to increased concentrations of potentially harmful levels of metals - especially zinc - that are correlated to elevated oxidative DNA damage," said Prue Talbot , a professor of cell biology , who led the research team. (universityofcalifornia.edu)
  • Recent data showing that Tax hijacks key mediators of DNA double-strand break repair signaling-the ubiquitin E3 ligase, ring finger protein 8 (RNF8) and the ubiquitin E2 conjugating enzyme (UBC13)-to activate the canonical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) and other signaling pathways will be discussed. (nih.gov)
  • Progress is being made in recognizing the patterns of response in genes and pathways induced by certain chemicals or chemical classes that might be predictive of adverse health outcomes in humans. (nih.gov)
  • BCL2 protein family, through its role in regulation of apoptotic pathways, is possibly related to cancer pathophysiology and resistance to conventional chemotherapy. (hindawi.com)
  • Various types of DNA damage are repaired through multiple repair pathways, such as base excision, nucleotide excision, homologous recombination and nonhomologous end joining. (springer.com)
  • Most of these proteins were involved in metabolism pathways, survival and pathogenicity of Leishmania parasites. (who.int)
  • The proteins identified in metabolism pathways, survival and pathogenicity of Leishmania parasites are possible targets that could be used for the diagnosis and treatment of canine visceral leishmaniasis and the development of vaccines against the disease in the future. (who.int)
  • Several DNA repair pathways work to protect the genome from genotoxic stresses. (dovepress.com)
  • Shelterin represses six distinct DNA damage response pathways. (rockefeller.edu)
  • These include the two main DNA damage signaling pathways, initiated by the ATM and ATR checkpoint kinases, and the DNA double-strand break (DSB) repair pathways involving homology-directed repair (HDR) and non-homologous end joining (NHEJ). (rockefeller.edu)
  • Shelterin is compartmentalized such that different subunits repress distinct DNA damage response pathways. (rockefeller.edu)
  • What pathways are this gene/protein implicaed in? (cancerindex.org)
  • The DNA in our cells is under constant attack from reactive chemicals generated as byproducts of cellular metabolism. (scienceblog.com)
  • Reactive oxygen species-induced activation of DNA binding protein NF-kappaB and antisense MT/HO studies are ongoing. (cdc.gov)
  • It has been known for several years that exposure to some xenohormones increases the production of reactive oxygen species, which in turn could inflict structural damage to cell DNA of target organs, as well as to DNA from other systemic cells [4, 5]. (researchgate.net)
  • On the other hand, it has been reported that exposure to some xenoestrogens and to estrogenic metabolites promotes the production of free radicals through the hydrogen peroxide (H 2 O 2 ) reduction cycle, by means of the P 450 oxidase and reductase enzymes, giving origin to the production of oxygen reactive species which might damage the genetic material [33]. (researchgate.net)
  • at lower levels, however, these agents still increase reactive oxygen species (ROS), damage DNA, and impede DNA repair. (nih.gov)
  • Reactive carbonyl species (RCS) such as methylglyoxal and glyoxal are potent glycolytic intermediates that extensively damage cellular biomolecules leading to genetic aberration and protein misfolding. (elifesciences.org)
  • This paper reports the important discovery of a mechanism of cellular response to the reactive carbonyl species, which in yeast involves Hsp31, Hsp32, Hsp33, and Hsp34, all orthologs of DJ-1 protein, a determinant of Parkinson's disease. (elifesciences.org)
  • The evidence supporting the role of Hsp31-34 in preventing and repairing damage to mitochondria, proteins and nucleic acids by reactive carbonyl species is convincing. (elifesciences.org)
  • Reactive carbonyl species (RCS) are highly toxic compounds that covalently bind and damage vital cellular components such as protein, DNA, and fatty acids ( Semchyshyn, 2014 ). (elifesciences.org)
  • In addition, this session will also deal with the photo-repair of nucleic acids and proteins. (rsc.org)
  • The structural and functional integrity of nucleic acids and proteins is critical for establishing a physiological balance to maintain normal cellular health. (elifesciences.org)
  • When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur, including double-strand breaks and DNA crosslinkages (interstrand crosslinks or ICLs). (wikipedia.org)
  • BCL2 family of proteins is the hallmark of apoptosis regulation. (hindawi.com)
  • In the present paper, we describe current knowledge on the role of BCL2 apoptosis regulator proteins in acute and chronic leukemias. (hindawi.com)
  • The morphological changes of apoptosis found in most cell types include nuclear pyknosis, DNA fragmentation and chromatin condensation, cytoskeleton destruction, membrane blebbing, and eventually the formation of membrane apoptotic bodies, which are phagocytosed by macrophages and other cells without promoting inflammatory response [ 1 ]. (hindawi.com)
  • The mechanism of apoptosis is evolutionarily conserved and is executed by a family of proteins, called caspases. (hindawi.com)
  • DNA damages can lead to cell mutation, death, apoptosis and immune system activation. (springer.com)
  • The function of these genes or their protein products is involved in the regulation of growth and apoptosis. (nih.gov)
  • 1 Typically, genomic integrity is protected by a series of processes, including DNA damage repair, cell cycle checkpoints, and apoptosis. (dovepress.com)
  • the wt-p53 protein is a primary mediator of cell cycle arrest, DNA repair and apoptosis. (spandidos-publications.com)
  • Special emphasis is directed towards recent literature on the mechanisms of action of these two proteins and the roles of Tax and HBZ in influencing the outcomes of HTLV-1 infection including senescence induction, viral latency and persistence, genome instability, cell proliferation, and ATL development. (nih.gov)
  • The characteristics of its genome--a aplastic anemia, hemorrhage, and lymphoid depletion) and single, closed molecule of circular, negative-sense DNA increased death in young chicken ( 11 ). (cdc.gov)
  • The genome of HGyV, which resembles CAV more aimed at defi ning the prevalence of HGyV infection in closely than other members of the family ( 1 , 3 ), contains different human populations, portal of entry, type of cells an untranslated region of 380 nt and 3 major partially targeted during primary amplifi cation, and site of latency/ overlapping open reading frames (named viral protein [VP] persistence. (cdc.gov)
  • DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encodes its genome . (wikipedia.org)
  • The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functionality of that organism. (wikipedia.org)
  • BRCA2 has a central role in maintaining genome integrity by facilitating the repair of toxic DNA double-strand breaks (DSBs) by homologous recombination (HR). BRCA2 acts by controlling RAD51 nucleoprotein filament formation on resected single-stranded DNA, but how BRCA2 activity is regulated during HR is not fully understood. (nature.com)
  • The human genome is made up of nearly two metres of DNA that must be compacted into a nucleus of just a few microns in diameter. (ncl.ac.uk)
  • The intricate task of genome maintenance is promoted by myriads of proteins involved in preventing, recognizing and resolving DNA damage. (nmt.edu)
  • SV40 fragment integration into the zebrafish embryonic genome was detected by Southern blot using a DNA probe for the SV40 terminator. (dovepress.com)
  • de Lange seeks to understand how telomeres are protected from the DNA damage response by a protein complex called shelterin, how they are replicated and maintained, and how telomere shortening contributes to tumor suppression and genome instability in cancer. (rockefeller.edu)
  • Her research is focused on understanding how cells respond to DNA damage and safeguard the integrity of the genome. (mdanderson.org)
  • Using confocal microscopy, we found that the APE1 in both wild-type and NPMc+ mutant cell lines is predominately localised in the cytoplasm, while it is translocated into the nucleus after the cells were exposed to MMS, presumably to play a role in the DNA damage repair mechanism. (nottingham.ac.uk)
  • A novel mechanism of acid and bile acid-induced DNA damage involving Na+/H+ exchanger: implication for Barrett's oesophagus. (nih.gov)
  • The major goal of this study was to determine the mechanism responsible for bile acid-induced alteration in intracellular pH (pH(i)) and its effect on DNA damage in cells derived from normal oesophagus (HET1A) or Barrett's oesophagus (CP-A).Cells were exposed to bile acid cocktail (BA) and/or acid in the presence/absence of inhibitors of nitric oxide synthase (NOS) or sodium-hydrogen exchanger (NHE). (nih.gov)
  • Examination of biopsies and cell lines revealed robust expression of NHE1 in Barrett's oesophagus but an absence of NHE1 in normal epithelium.The results of this study identify a new mechanism of bile acid-induced DNA damage. (nih.gov)
  • Increased DNA repair in tumors that removes DNA lesions generated by therapeutic agents before they became toxic is a major mechanism to develop therapy resistance. (nist.gov)
  • MECHANISM OF SUPPORT Only applications using the NIH individual research project grant (R01) award mechanism will be accepted in response to this RFA. (nih.gov)
  • Interpretation of the mechanism and dynamics of photoexcited state processes is of paramount importance to understanding DNA oxidative damage. (rsc.org)
  • The mechanism and dynamics of photoinduced DNA and protein damage is critically important to our understanding of diseases associated with ultraviolet irradiation as well as to the development of photosensitized therapies. (rsc.org)
  • IBy discovering that the protein huntingtin can control ciliogenesis, Keryer and colleagues have revealed a new pathogenic mechanism in Huntington disease (page 4372). (jci.org)
  • A key component of the telomere protecting mechanism is a multi-protein complex called shelterin. (sciencedaily.com)
  • Importantly, the modulation of chromatin structure is a key mechanism for regulating the function of the underlying DNA and as such, chromatin represents a fundamental layer of epigenetic control. (ncl.ac.uk)
  • Moffitt Cancer Center researchers have discovered a novel mechanism that controls a cell's response to DNA damage. (phys.org)
  • To confirm the specificity of DNA-damage related modulation, several anti-leukemic drugs has been tested and we did confirm that the proposed mechanism impairs cell death upon daunorubicin-induced DNA damage of human lymphoid cells. (whiterose.ac.uk)
  • In conclusion, our study uncovers new insights into SHOC2 function and reveals that this scaffold protein may be essential to activate a novel mechanism of p53-induced cell death in pre-B lymphoid cells. (whiterose.ac.uk)
  • If not repaired properly, the damage leads to mutations, which over time can cause cancer. (scienceblog.com)
  • For example, in the hereditary cancer syndromes familial adenomatous polyposis or hereditary nonpolyposis colorectal cancer, mutations have been discovered in the APC gene and DNA mismatch repair genes. (medscape.com)
  • Most mutations replace single protein building blocks (amino acids) in senataxin. (medlineplus.gov)
  • DNA/RNA helicase gene mutations in a form of juvenile amyotrophic lateral sclerosis (ALS4). (medlineplus.gov)
  • Fogel BL, Perlman S. Novel mutations in the senataxin DNA/RNA helicase domain in ataxia with oculomotor apraxia 2. (medlineplus.gov)
  • Photoinduced charge transfer processes have been implicated in a variety of oxidative processes which ultimately lead to mutations, compromising the biological function of DNA. (rsc.org)
  • The study, published online in Nature Communications, explains how a group of genetic mutations associated with this protein complex contributes to various cancers. (sciencedaily.com)
  • They found that some of these mutations reduce the affinity between the two proteins and, consequently, their ability to bind to telomeric DNA efficiently, whereas others perturb the POT1 structure. (sciencedaily.com)
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Interestingly, 4 of the indel mutations led to aberrant splicing, which may produce a different protein than predicted from the genomic sequence. (cancerindex.org)
  • In yeast, CtIP is required for resection of the broken end, and since it is also recruited to sites of DNA damage in human cells, Hunter's team wanted to know whether CtIP plays a similar role there. (scienceblog.com)
  • We show that the phosphorylation-dependent formation of the BRCA2-PP2A-B56 complex is required for efficient RAD51 filament formation at sites of DNA damage and HR-mediated DNA repair. (nature.com)
  • An N-terminal PALB2 interaction domain recruits BRCA2 to sites of DNA damage as part of the BRCA1-PALB2-BRCA2 complex 12 . (nature.com)
  • RPA recruits multiple proteins to sites of DNA damage via the N-terminal domain of the 70 kDa subunit (RPA70N). (rcsb.org)
  • 2) How does chromatin modification at sites of DNA damage regulate DNA repair and transcription? (mdanderson.org)
  • The percentage and kinetics of DNA damage in both cell lines was identical, indicating that DNA lesions were repaired efficiently in both the wild-type and mutant cell lines. (nottingham.ac.uk)
  • Oxidatively induced DNA damage is caused in living organisms by a variety of damaging agents, resulting in the formation of a multiplicity of lesions, which are mutagenic and cytotoxic. (nist.gov)
  • [1] In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage, resulting in tens of thousands of individual molecular lesions per cell per day. (wikipedia.org)
  • [2] Many of these lesions cause structural damage to the DNA molecule and can alter or eliminate the cell's ability to transcribe the gene that the affected DNA encodes. (wikipedia.org)
  • DNA damage, due to environmental factors and normal metabolic processes inside the cell, occurs at a rate of 10,000 to 1,000,000 molecular lesions per cell per day. (wikipedia.org)
  • It appears from literature that human cytomegalovirus enhances DNA repair capacity in host cells, without producing detectable lesions in cellular DNA or inhibiting DNA synthesis (Nishiyama and Rapp 1981 ). (springer.com)
  • DNA interstrand crosslinks (ICLs) are the most toxic lesions induced by chemotherapeutic agents such as mitomycin C and cisplatin. (xenbase.org)
  • Studies on ICL signaling and repair have been limited, because these drugs generate additional DNA lesions that trigger checkpoint signaling. (xenbase.org)
  • In conclusion, perturbation of NPM1 subcellular localisation in NPMc+AML has no effect on the DNA repair mechanisms but we found differences in the anti-apoptotic proteins expression compared to NPM1 wild-type cells. (nottingham.ac.uk)
  • Still, the detailed mechanisms of action of SMC proteins remain to be determined. (wikipedia.org)
  • The 2015 Nobel Prize in Chemistry was awarded to Tomas Lindahl , Paul Modrich , and Aziz Sancar for their work on the molecular mechanisms of DNA repair processes. (wikipedia.org)
  • Dr. Burg's group has been studying this phenomenon, to uncover the mechanisms by which renal cells escape the known dangerous consequences of persistent DNA damage. (nih.gov)
  • Changes in the activity of DNA repair proteins during viral infection can cause disturbances in the DNA repair system and change its mechanisms. (springer.com)
  • The control aspects of the five DNA repair mechanisms in virus-infected cells have not been well characterized. (springer.com)
  • Fanconi Anaemia (FA) is a cancer predisposition disorder characterised by chromosome fragility and hypersensitivity to genotoxic agents that suggest defects in the molecular mechanisms of DNA damage signalling and repair. (embl.de)
  • The accumulation of DNA damage and the cellular response to DNA damage stressors was more pronounced in post-mitotic mFUS motoneurons than in dividing hiPSCs suggesting that mFUS motoneurons accumulate foci of DNA damage, which in turn might be directly linked to neurodegeneration. (frontiersin.org)
  • This is related to the fact that during night there is no sun light which has damaging effect on DNA and amount of active products of metabolism, also damaging to DNA, is minimized. (life-enthusiast.com)
  • Although senataxin's role in cells is not completely understood, it appears to be involved in the production of proteins from genes (transcription), the processing of RNA molecules, and the repair of damaged DNA. (medlineplus.gov)
  • Static and kinetic site-specific protein-DNA photocrosslinking has major implications for transcription in general, for the topology determinants specifically for RNA polymerase II transcription, and the mechanistic determinants of contacts involved in nucleoprotein complexes. (rsc.org)
  • the result of this translocation is the enhanced BCL2 protein transcription. (hindawi.com)
  • My research centred upon the role of DNA topology in control of transcription initiation from σ 54 -dependent promoters. (ncl.ac.uk)
  • Red No. 3, beta-estradiol, and DDT increase ER site-specific DNA binding to the estrogen response element in HTB 133 cells and increase cyclin-dependent kinase 2 activity in MCF-7 breast cancer cells. (researchgate.net)
  • Loss of WASp impedes nuclear translocation of GOLPH3 and its colocalization with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). (psu.edu)
  • This activation is mediated via their proteins binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. (nih.gov)
  • SQ/TQ cluster domains: concentrated ATM/ATR kinase phosphorylation site regions in DNA-damage-response proteins. (philpapers.org)
  • The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA crosslinks into double-strands breaks. (xenbase.org)
  • We investigated the presence of HGyV DNA in 1, VP2, and VP3) that encode proteins of 465, 231, and blood samples of 301 persons in Italy using specifi c PCRs. (cdc.gov)
  • NPM1 interacts with many proteins including those that participate in DNA damage repair processes. (nottingham.ac.uk)
  • This may have a role in the sensitivity of mutant cells to chemotherapy via inactivation of the DNA damage response processes. (nottingham.ac.uk)
  • In sharp contrast, however, information on electronic processes in biomolecules such as isolated proteins and DNA (and their complexes) is still in its infancy. (rsc.org)
  • Such processes in DNA are also of interest to both the biological and materials communities as memory devices and structural building blocks. (rsc.org)
  • ii) response to light and ii) electron transfer processes in a variety of organisms are subjects of great importance. (rsc.org)
  • This session will discuss recent progress in the photoinduced processes related to proteins that are responsible for vision that include i) rhodopsin in the photoreceptor cells of the vertebrate ii) retina, phytochrome in plants, and bacteriorhodopsin and bacteriophytochromes in some bacteria. (rsc.org)
  • Photoinduced inter-protein electron transfer is also responsible for various biological processes. (rsc.org)
  • This session will highlight the consequences of photoinduced processes in DNA or proteins responsible for the onset of various types of disease (particularly melanoma cancer). (rsc.org)
  • The FUS gene codes for a multifunctional RNA/DNA-binding protein that is primarily localized in the nucleus and is involved in cellular processes such as splicing, translation, mRNA transport and DNA damage response. (frontiersin.org)
  • As the processes and proteins that we study have been highly conserved throughout evolution, our fission yeast studies provide insight into how the function of chromatin is controlled in humans and how aberrant chromatin structure results in disease states. (ncl.ac.uk)
  • The members of the DNA Repair Interest Group perform research in areas including DNA repair enzymology and fine structure, mutagenesis, gene and cell cycle regulation, protein structure, and human disease. (nih.gov)
  • Following damage, the TLRs interact with the tumor suppressor gene p53 to regulate the amount of inflammation. (nih.gov)
  • Tissue slide-based morphology-driven assays use archived formalin-fixed paraffin-embedded (FFPE) specimens to determine gene copy number by fluorescence in situ hybridization, mRNA or miRNA levels by in situ hybridization (ISH) and protein levels by immunohistochemistry (IHC). (medscape.com)
  • For protein-encoding genes, gene ontology analysis provides annotated information on expression and function that facilitates ascribing changes in mRNA levels to a specific cell type. (medscape.com)
  • The protein encoded by this gene belongs to the polycomb-like protein family, which is a component of polycomb repressive complex-2. (nih.gov)
  • The SETX gene provides instructions for making a protein called senataxin. (medlineplus.gov)
  • Senataxin plays an essential role with DNA damage response proteins in meiotic recombination and gene silencing. (medlineplus.gov)
  • Accordingly, the objective of this request for applications (RFA) is to encourage innovative, mechanistically based research using transgenic technologies to investigate the alterations of gene expression induced by environmental agents in specific target cells and organs, and to determine how this response varies at critical times during exposure. (nih.gov)
  • Perhaps the best examples of gene environment interactions at the molecular level have come from studies of metabolic enzymes and DNA repair proteins. (nih.gov)
  • ToxTracker consists of a panel of six different mES GFP reporter cell lines representing four distinct biological responses that are associated with carcinogenesis, i.e. general cellular stress (biomarker gene: Btg2), DNA damage (biomarker genes: Bscl2 and Rtkn), oxidative stress (biomarker genes: Srxn1 and Blvrb) and protein damage (biomarker gene: Ddit3). (europa.eu)
  • Our research adds a piece of the puzzle toward solving the intricate structure of the shelterin complex, a fundamental player in the maintenance of telomere DNA integrity," said Emmanuel Skordalakes, Ph.D.,Associate Professor in the Gene Expression and Regulation Program at Wistar and lead author of the paper. (sciencedaily.com)
  • From NCBI Gene: This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. (nih.gov)
  • What does this gene/protein do? (cancerindex.org)
  • Based on the structure of senataxin, researchers believe that it is one of a class of proteins called helicases, which attach to particular regions of DNA or RNA (a chemical cousin of DNA) and temporarily unwind the strands of the molecule. (medlineplus.gov)
  • The reactions were conducted in initiation of the study, had received no antiretroviral a 50-L PCR mixture containing Taq DNA polymerase, treatment. (cdc.gov)
  • During short-patch BER, 5′dRP is displaced by DNA polymerase β (Polβ), which inserts a single nucleotide. (springer.com)
  • Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint. (xenbase.org)
  • CST is a trimeric ssDNA binding complex that is associated with DNA polymerase αprimase. (rockefeller.edu)
  • 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)
  • Defects in the ability of cells to properly respond to and repair DNA damage result in genomic instability and underlie many forms of cancer. (mdanderson.org)
  • Evidence suggests that DNA repair capacity may be a predictive biomarker of patient response. (nist.gov)
  • As a major defense against environmental damage to cells DNA repair is present in all organisms examined including bacteria, yeast, drosophila, fish, amphibians, rodents and humans. (nih.gov)
  • The γ-H2AX foci were also evaluated which increased to similar levels in mutant and wild-type cells lines after exposure to DNA damaging agents and decreased with similar rates when the cells were allowed 24 hours to repair the damage. (nottingham.ac.uk)
  • Interestingly, following DNA damage, the amount of NPM1 increased significantly in NPMc+ cells, both in the nucleus and the cytoplasm, which was not seen in NPM1 wild-type cells. (nottingham.ac.uk)
  • As we could find no apparent difference in DNA repair between NPM1 mutated and wild type cells we went on to look at proteins involved in cell survival - BCL-2 and MCL-1. (nottingham.ac.uk)
  • We will try to determine if their cells behave differently, and if these subjects have changes in their inflammatory response, or an increased risk for certain inflammatory diseases. (nih.gov)
  • La Jolla, CA - In order to preserve our DNA, cells have developed an intricate system for monitoring and repairing DNA damage. (scienceblog.com)
  • To find out, they depleted CtIP from human cells and caused DNA damage. (scienceblog.com)
  • Without the CtIP, they discovered, the cells could no longer trim back the damaged DNA strands, which brought the whole repair process to an abrupt halt. (scienceblog.com)
  • In this way, CtIP is like a switchblade that cells open only in the presence of DNA damage. (scienceblog.com)
  • Pro-oxidant responses of respiratory cells to organic dust extracts. (cdc.gov)
  • Our evidence suggests that lung cells respond in a qualitatively, but not quantitatively, similar fashion following exposures to grain dust extracts vs. purified endotoxin, suggesting the participation of other agents in toxic responses of lung to organic dusts. (cdc.gov)
  • AM cells demonstrated a rapid pro-oxidant response to dust extracts, including production of hydrogen peroxide and interleukin-l as detected by immunoassay, which was followed 24 hr later by single-stranded DNA damage as measured by gel electrophoresis and immunoassay. (cdc.gov)
  • Epithelial cells lacked the pro-oxidant responses, but did display DNA damage after prolonged 3 day exposures. (cdc.gov)
  • These data support a role for oxidative injury to respiratory cells following exposures to particulates, and potential protective responses by stress proteins. (cdc.gov)
  • Our laboratory has developed methodologies that use mass spectrometry with isotope dilution for the measurement of expression of DNA repair proteins in human and cultured cells. (nist.gov)
  • Site-specific DNA binding by p53 in RLE, HTB 125, HTB 133, and MCF-7 cells was increased when they were treated with Red No. 3, which suggests that cellular DNA was damaged by this colorant. (researchgate.net)
  • Although it is unclear how impaired senataxin function leads to the signs and symptoms of ataxia with oculomotor apraxia type 2, some researchers suggest that it disrupts DNA repair and can lead to an accumulation of DNA damage in cells. (medlineplus.gov)
  • Results: WASp deficiency completely prevents the development of IR-induced GDR in human T H and B cells, despite the high DNA damage load. (psu.edu)
  • Surprisingly, however, depletion of GOLPH3 alone or depolymerization of F-actin in WASp-sufficient T H cells still allows development of robust GDR, suggesting that WASp, but not GOLPH3, is essential for GDR and cell survival after IR-induced DNA-damage in human lymphocytes. (psu.edu)
  • The lab has also been investigating the damage that occurs to renal cells when NaCl and urea are elevated. (nih.gov)
  • Database of osmoregulated proteins in mammalian cells. (nih.gov)
  • DNA-protein crosslinking in human white blood cells is as high as 0.5-4.5 per 107 bases and is found to increase as a function of age. (rsc.org)
  • To that end, we compared cells carrying a mild or severe mFUS in physiological- and/or stress conditions as well as after induced DNA damage. (frontiersin.org)
  • Following hyperosmolar stress or irradiation, mFUS hiPS cells recruited significantly more cytoplasmatic FUS into stress granules accompanied by impaired DNA-damage repair. (frontiersin.org)
  • Although the function of this protein is unclear, it appears to play an important role in nerve cells (neurons) in the brain. (medlineplus.gov)
  • The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. (medlineplus.gov)
  • By contrast, they are induced by various forms of cell stress, most notably DNA damage, which is very common in cancer cells. (mdpi.com)
  • By this means, NKG2D provides a rapid response system to detect and eradicate potentially dangerous cells. (mdpi.com)
  • Tonicity-responsive enhancer-binding protein (TonEBP), which is also known as nuclear factor of activated T cells 5 (NFAT5), was discovered 20 years ago as a transcriptional regulator of the cellular response to hypertonic (hyperosmotic salinity) stress in the renal medulla. (nature.com)
  • Also, their absence elevates DNA damage response, making cells vulnerable to various genotoxins. (elifesciences.org)
  • If the DNA is not repaired, cells may begin growing uncontrollably, leading to the development of cancer. (phys.org)
  • Therefore, cells must maintain an intricate regulatory network to ensure that their DNA remains intact. (phys.org)
  • These results are important because they increase scientists' understanding of how proteins and cells function, potentially leading to more effective therapeutic drugs in the future. (phys.org)
  • To address such paradoxical function, our study investigated how SHOC2 impact leukemic cells drug response. (whiterose.ac.uk)
  • Proteomic techniques can show the proteome profile of cells and biological fluids and can also provide more information on protein functions and post-translational modifications of proteins (5). (who.int)
  • We are also interested in developing anti-cancer drugs that create DNA damage and trigger cell death exclusively in cancer cells. (nmt.edu)
  • DNA damage induced by KP372-1 hyperactivates PARP1 and enhances lethality of pancreatic cancer cells with PARP inhibition.Viera T, Patidar PL. Sci Rep. 2020 Nov 19;10(1):20210. (nmt.edu)
  • It is widely accepted that DNA double-strand breaks (DSBs) and their misrepair in stem cells are critical events in the multistage origination of various leukemias and tumors, including gliomas. (nih.gov)
  • DNA double-strand breaks (DSBs) are considered to be the most lethal type of DNA damage in cells. (dovepress.com)
  • Damage-resistant DNA synthesis in Fanconi anemia cells treated with a DNA cross-linking agent. (xenbase.org)
  • Deficiency in incisions produced by XPF at the site of a DNA interstrand cross-link in Fanconi anemia cells. (xenbase.org)
  • de Lange and her colleagues determined the fate of telomeres lacking one or more of the six shelterin subunits, showing that cells perceive their natural chromosome ends as damaged DNA when shelterin is compromised. (rockefeller.edu)
  • The LxxIxE motif in BRCA2 is embedded in a hitherto uncharacterized region between BRC repeat 1 and 2 comprising residues 1102-1132, which is highly conserved spanning more than 450 million years of evolution (190 full-length vertebrate BRCA2 protein sequences analyzed by Clustal Omega multiple sequence alignment) (Fig. 1b and Supplementary Data 1 ). (nature.com)
  • Besides the glyoxalase system, emerging studies report highly conserved DJ-1 superfamily proteins as critical regulators of RCS. (elifesciences.org)
  • Dr. Burg's lab has identified the amino acids in NFAT5 that become phosphorylated, as well as protein kinases, phosphatases, and other proteins that are involved. (nih.gov)
  • RPS26 is a recently identified Diamond-Blackfan Anemia-related ribosomal protein and its role in p53 activation has not been previously explored. (nih.gov)
  • TLRs are proteins that play a role in the immune system by defending the body from infection. (nih.gov)
  • In a forthcoming article in the Dec. 24 issue of Molecular Cell , they show that a protein named CtIP plays an essential role in the DNA damage "signal-to-repair" conversion process. (scienceblog.com)
  • In a subclass of Gram-negative bacteria, including Escherichia coli, a distantly related protein known as MukB plays an equivalent role. (wikipedia.org)
  • The genotoxic action of contaminating agents affects human health directly, damaging the genetic material, which is considered to play an important role in oncogenesis [6,7]. (researchgate.net)
  • The genotoxicity of some environmental contaminants may affect human health directly by damaging genetic material and thus plays an important role in cancer development. (researchgate.net)
  • Objective: We sought to define WASp's role in the DNA damage-induced GDR and its disruption as a contributor to the development of radiosensitivity-linked immunodeficiency in patients with WAS. (psu.edu)
  • Niacinamide is a component of NAD and NADP, essential coenzymes in ATP production, also having a central role in DNA repair and skin homeostasis. (dsm.com)
  • Current research focuses on the prognostic impact and specific role of these proteins in the pathogenesis of leukemias. (hindawi.com)
  • Members of the Macromolecular Structure and Dynamics Group study the role that specific proteins and protein systems play in certain diseases, with a focus on understanding protein function at the atomic and molecular levels. (uwo.ca)
  • In this review, considerations and results of the experiments are presented, supporting the thesis on the important role of DNA repair systems in HCMV- infected cell. (springer.com)
  • The protein SIRT1 plays an important role in controlling DNA damage. (phys.org)
  • Research shows that the day-night cycle plays important role in DNA regeneration in cellular structure [1-4]. (life-enthusiast.com)
  • Studies how telomeres protect chromosome ends from the DNA damage response and the role of telomeres in cancer. (rockefeller.edu)
  • In addition to protecting telomeres, shelterin plays a major role in the maintenance of telomeric DNA. (rockefeller.edu)
  • Ovarian cancer (OC) is a heterogeneous disease characterized by defective DNA repair. (nih.gov)
  • He said that the publication had two main findings: humans evolved an inflammatory response when subjected to DNA damage, and the variation in TLR activity among humans suggests that some people are more prone to inflammation following DNA damage, for example, after receiving cancer therapy. (nih.gov)
  • the cell has to know when it has received this type of damage and respond appropriately," explains Tony Hunter, Ph.D., American Cancer Society Professor in the Molecular and Cell Biology Laboratory and director of the Salk Institute Cancer Center, who led the study. (scienceblog.com)
  • As a result, individuals with an inherited impairment in DNA repair capability are often at increased risk of cancer," notes first author Zhongsheng You, Ph.D., a former postdoctoral researcher at the Salk Institute and now an assistant professor at Washington University School of Medicine in St. Louis. (scienceblog.com)
  • Cancer tissues develop greater DNA repair capacity than normal tissues by overexpressing DNA repair proteins. (nist.gov)
  • Malign consequences of mis-function in higher life forms can include blindness (retinal pigmentosa), as well as photomutation leading, in DNA, to the primary cause of various types of cancer which (when light induced) can lead to melanomas. (rsc.org)
  • He is co-investigator and coordinator of the Columbus Breast Cancer Tissue Bank (Maryam Lustburg, MD, PI), a tissue archive service collecting DNA, RNA, cell lines, tissue samples, tissue microarrays and clinical data on women diagnosed with breast cancer in the Columbus area. (osu.edu)
  • Interdisciplinary approaches including protein biochemistry, cell & molecular biology, cancer biology, genomics, proteomics and RNAi are routinely employed to drive on-going research. (nmt.edu)
  • KP372-1-induced DNA damage as a chemotherapeutic approach to treat cancer", Patidar P.L. and Viera, T., U.S. Provisional Patent Application No. 63/111,994. (nmt.edu)
  • We analyzed tumor suppressor TP53 binding protein 1 (53BP1) foci that are typically formed at the sites of DSB location (referred to as DNA repair foci) by laser confocal microscopy. (nih.gov)
  • DNA double-strand breaks (DSBs) and their misrepair are critical molecular events resulting in chromosomal aberrations, which have often been associated with origination of various leukemias and tumors, including gliomas ( Fischer and Meese 2007 ). (nih.gov)
  • Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. (cancerindex.org)
  • Researchers offer the first evidence that DNA damage can lead to the regulation of inflammatory responses, the body's reaction to injury. (nih.gov)
  • The proteins involved in the regulation help protect the body from infection. (nih.gov)
  • More straightforward interpretations of miRNA function can be drawn based on expression changes of protein function, as mature miRNA levels generally correlate with miRNA activity, whereas post-transcriptional regulation and post-translational modifications render a more complex correlation between protein activity and expression levels of mRNAs or proteins. (medscape.com)
  • The authors believe that exposure of CtIP 's DR domain and its recruitment to the site of DNA damage triggers a chain reaction that results in DNA repair, and they now want to understand exactly what CtIP does to start the DNA repair process. (scienceblog.com)
  • abstract = "Background: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immune deficiency disorder resulting from Wiskott-Aldrich syndrome protein (WASp) deficiency. (psu.edu)
  • The lab identified a six-subunit protein complex, which they named shelterin, that specifically binds to telomeres. (rockefeller.edu)
  • Firstly, we aimed to identify potential differences in DNA repair in response to double-strand breaks (DSB) and alkylating inducers and then assess them through the comet assay in the wild-type and mutant NPM1 cell lines. (nottingham.ac.uk)
  • As a result of this continuous bombardment, some studies have estimated that the DNA in a single human cell gets damaged over 10,000 times every day. (scienceblog.com)
  • Only when the cell sends a DNA damage signal is CtIP's DR domain exposed, and only then can CtIP bind to the broken DNA. (scienceblog.com)
  • Attempts are made to integrate results from cell-based studies of HTLV-1 infection and studies of HTLV-1 proviral integration site preference, clonality, and clonal expansion based on high throughput DNA sequencing. (nih.gov)
  • The rate of DNA repair is dependent on many factors, including the cell type, the age of the cell, and the extracellular environment. (wikipedia.org)
  • Lymphocytes from patients with WAS manifest increased DNA damage and lymphopenia from cell death, yet how WASp influences DNA damage-linked cell survival is unknown. (psu.edu)
  • Methods: In human T H and B-cell culture systems, DNA damage-induced GDR elicited by IR or radiomimetic chemotherapy was monitored in the presence or absence of WASp or GOLPH3 alone or both together. (psu.edu)
  • BCL2 protein was found to inhibit cell death. (hindawi.com)
  • The immune system provides surveillance measures to identify and remove damaged cell types at an early stage. (mdpi.com)
  • Unrepaired DNA damage can lead to mutation, development of various diseases or cell death (Bartek et al. (springer.com)
  • Only several of those studies report some evidence of increased cell repair capacity after infection or viral protein overexpression (Chipitsyna et al. (springer.com)
  • It can sense the presence of DNA damage, signal to other proteins that damage exists, aid in the repair of damage and stimulate cell death if the damage cannot be repaired. (phys.org)
  • This modification allows SIRT1 to relay information about DNA damage to other proteins, leading to either DNA repair or cell death. (phys.org)
  • Our data suggest that cell sensitivity to crosslinking agents results from both checkpoint and DNA repair defects. (xenbase.org)
  • DNA consists of two intertwined strands so that when the DNA is broken, two ends are revealed, one from each strand. (scienceblog.com)
  • By unwinding the strands, helicases allow other proteins to reach the strands to perform their function. (medlineplus.gov)
  • Eukaryotes have at least six SMC proteins in individual organisms, and they form three distinct heterodimers with specialized functions: A pair of SMC1 and SMC3 constitutes the core subunits of the cohesin complexes involved in sister chromatid cohesion. (wikipedia.org)
  • Some organisms have variants of SMC proteins. (wikipedia.org)
  • The following table shows the SMC proteins names for several model organisms and vertebrates: SMC proteins are conserved from bacteria to humans. (wikipedia.org)
  • A dimer composed of SMC5 and SMC6 functions as part of a yet-to-be-named complex implicated in DNA repair and checkpoint responses. (wikipedia.org)
  • 2009), Checkpoint signaling from a single DNA interstr. (xenbase.org)
  • Checkpoint signaling from a single DNA interstrand crosslink. (xenbase.org)
  • Characterization of estrogen-induced F-box protein FBXO45. (nih.gov)
  • The following human genes encode SMC proteins: SMC1A SMC1B SMC2 SMC3 SMC4 SMC5 SMC6 Wikimedia Commons has media related to SMC proteins. (wikipedia.org)
  • By 2003, 99% of the chemical base pairs that make up human DNA had been sequenced to within 99.99% accuracy (with the sequencing reported to have reached 100% by 2021). (medscape.com)
  • Human gyrovirus (HGyV) is a recent addition to of HGyV and CAV (for which the coded protein has been the list of agents found in humans. (cdc.gov)
  • For this purpose, full length 15N-labeled analogs of a number of human DNA repair proteins have been produced and purified to be used as internal standards for positive identification and accurate quantification. (nist.gov)
  • Niacinamide PC significantly reduces ROS and carbonylated proteins levels in human skin in response to blue light irradiation. (dsm.com)
  • Niacinamide has been shown to enhance the repair of DNA damage in human keratinocytes and in human skin. (dsm.com)
  • Herpesvirus infections, such as those induced by human cytomegalovirus (HCMV), induce specific DNA damages. (springer.com)
  • Human cytomegalovirus (HCMV) is a member of the betaherpesvirus subfamily and encodes more than 200 viral proteins (Chee et al. (springer.com)
  • DJ-1 superfamily proteins, including the human DJ-1, a genetic determinant of Parkinson's disease, possess diverse physiological functions paramount for combating multiple stressors. (elifesciences.org)
  • Tonicity-responsive enhancer-binding protein (TonEBP) is a stress protein involved in the cellular response to hypertonicity, autoimmune reactions, inflammation and metabolic and genotoxic stress. (nature.com)
  • The ATP-binding domain of SMC proteins is structurally related to that of ABC transporters, a large family of transmembrane proteins that actively transport small molecules across cellular membranes. (wikipedia.org)
  • Once CtIP is recruited, resection and repair begin, so regulating CtIP recruitment is one way to regulate DNA repair itself. (scienceblog.com)
  • DNA damage response inhibition and therapeutic strategies. (nih.gov)
  • TonEBP-mediated responses to autoimmunity, viral infection and metabolic stresses are pathological. (nature.com)
  • In addition to proteins and protein fragments, DNA undergoes photocrosslinking with bound drugs. (rsc.org)
  • We evaluated substituents on the aromatic rings as well as the type and geometry of the linkers used to combine fragments, ultimately leading to submicromolar inhibitors of RPA70N protein-protein interactions. (rcsb.org)
  • Interestingly, yeast DJ-1 orthologs preserve functional mitochondrial content, maintain ATP levels, and redistribute into mitochondria to alleviate the glycation damage of macromolecules. (elifesciences.org)
  • The discovery of the structure of DNA by Francis Crick and James Watson in the early 1950s ushered in a new era in molecular biologic science. (medscape.com)
  • Fig. 6: Molecular actions of TonEBP in response to pathological stresses. (nature.com)
  • IHC is the most common assay for expression analysis of protein-encoding genes in routine clinical practice, as is ISH for expression of miRNAs in translational research. (medscape.com)
  • Those experimental studies focused on repairs of exogenously introduced damage in cellular DNA in the context of single viral protein expression (Becker et al. (springer.com)
  • The expression of vascular endothelial growth factor (VEGF), protein p53 and micro‑vessel density (MVD) in tumor tissue was respectively determined by immunohistochemistry. (spandidos-publications.com)
  • F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (summary by Jin et al. (nih.gov)