• Thermolabile UDG removes uracil from DNA by hydrolyzing the N-glycosylic bond between the deoxyribose and the base, leaving an apurinic or apyrimidinic site. (qiagen.com)
  • Here, we report that depletion of Tyrosyl DNA phosphodiesterase 1 (TDP1) sensitizes human cells to alkylation damage and the additional depletion of apurinic/apyrimidinic endonuclease I (APE1) confers hypersensitivity above that observed for TDP1 or APE1 depletion alone. (whiterose.ac.uk)
  • Quantification of DNA breaks and clonogenic survival assays confirm a role for TDP1 in response to base damage, independently of APE1. (whiterose.ac.uk)
  • APE1/Ref-1 is an essential DNA repair/gene regulatory protein in mammals of which intracellular level significantly affects cellular sensitivity to genotoxicants. (uky.edu)
  • The apurinic/apyrimidinic endonuclease 1 (APE1) functions are altered by phosphorylation and acetylation. (uky.edu)
  • Moreover, DNA-damaging reagents and nutlin-3, an inhibitor of MDM2-p53 interaction, increased APE1 ubiquitination in the presence of p53. (uky.edu)
  • Therefore, monoubiquitination not only is a prerequisite for degradation, but may also alter the APE1 activities in cells. (uky.edu)
  • The primary enzyme to repair AP sites in mammalian cells is the AP endonuclease (APE1), which functions through the base excision repair (BER) pathway. (unmc.edu)
  • Mammalian APE1 has a unique N-terminal unstructured tail and has both DNA repair and transcriptional regulatory activities. (unmc.edu)
  • However, the regulatory role of APE1 acetylation (AcAPE1) in the context of both DNA damage repair and transcriptional regulation has not been elucidated. (unmc.edu)
  • this, in turn, enhances the AP-endonuclease activity of APE1. (unmc.edu)
  • In the absence of APE1 acetylation, cells accumulated AP sites in the genome and showed higher sensitivity to DNA-damaging agents. (unmc.edu)
  • 8-OxoG levels in DNA were inversely correlated with the abundance of acetylated OGG1 (Ac-OGG1), but not with total OGG1, apurinic/apyrimidinic endonuclease 1 (APE1), or Ac-APE1. (elsevierpure.com)
  • The exonuclease activity of Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for processing matched/mismatched terminus in various DNA repair pathways and for removing nucleoside analogs associated with drug resistance. (nycu.edu.tw)
  • Apurinic/apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1) is a multifunctional protein that is essential in activating oncogenic transcription factors. (oncotarget.com)
  • Because APE1/Ref-1 is expressed and elevated in prostate cancer, we sought to characterize APE1/Ref-1 expression and activity in human prostate cancer cell lines and determine the effect of selective reduction-oxidation (redox) function inhibition on prostate cancer cells in vitro and in vivo . (oncotarget.com)
  • Due to the role of oncogenic transcriptional activators NFĸB and STAT3 in survivin protein expression, and APE1/Ref-1 redox activity regulating their transcriptional activity, we assessed selective inhibition of APE1/Ref-1's redox function as a novel method to halt prostate cancer cell growth and survival. (oncotarget.com)
  • Inhibition of APE1/Ref-1 redox function significantly reduced NFĸB transcriptional activity, survivin mRNA and survivin protein levels. (oncotarget.com)
  • XRCC1 stimulates the formation of the hOGG1 Schiff-base DNA intermediate without interfering with the endonuclease activity of APE1, the second enzyme in the pathway. (nih.gov)
  • The data presented support a model by which XRCC1 will pass on the DNA intermediate from hOGG1 to the endonuclease APE1. (nih.gov)
  • This results in an acceleration of the overall repair process of oxidized purines to yield an APE1-cleaved abasic site, which can be used as a substrate by DNA polymerase beta. (nih.gov)
  • They also suggest the existence of cross-talk between different Lys residues of APE1 occurring upon genotoxic damage, which may modulate APE1 subnuclear distribution and enzymatic activity in vivo. (uniud.it)
  • Apurinic/apyrimidinic endonuclease 1 (APE1) is a multifunctional protein contributing to genome stability via repair of DNA lesions via the base excision repair pathway. (cnr.it)
  • After the removal of adenine, the DNA was then cleaved, possibly by an associated lyase activity. (jefferson.edu)
  • Has AP (apurinic/apyrimidinic) lyase activity and introduces nicks in the DNA strand. (expasy.org)
  • Additionally, it was found that the removal of adenine by a single-strand DNA glycosylase activity was the first step in the cleavage of DNA. (jefferson.edu)
  • Link to all annotated objects annotated to DNA N-glycosylase activity. (planteome.org)
  • Link to all direct and indirect annotations to DNA N-glycosylase activity. (planteome.org)
  • This interaction leads to a 2- to 3-fold stimulation of the DNA glycosylase activity of hOGG1. (nih.gov)
  • 3'-5' exonuclease activity of human apurinic/apyrimidinic endonuclease 1 towards DNAs containing dNMP and their modified analogs at the 3 end of single strand DNA break. (neb.com)
  • Protein p56 encoded by the Bacillus subtilis phage phi29 inhibits host uracil-DNA glycosylase (UDG) activity. (nih.gov)
  • On the other hand, the action of UDG on uracil-containing phi29 DNA impaired in vitro viral DNA replication, which was prevented by the presence of protein p56. (nih.gov)
  • Furthermore, transfection activity of uracil-containing phi29 DNA was significantly higher in cells that constitutively synthesized p56 than in cells lacking this protein. (nih.gov)
  • Thus, our data support a model in which protein p56 ensures an efficient viral DNA replication, preventing the deleterious effect caused by UDG when it eliminates uracil residues present in the phi29 genome. (nih.gov)
  • Chapter One investigated an alternative activity of the plant ribosome-inactivating protein (RIP) gelonin, which was proposed to be responsible for the cytotoxicity seen in RIP treated P. falciparum. (jefferson.edu)
  • It is unlikely that the DNase activity of both the native and recombinant protein were due to a contaminant because nuclease activity gel analysis in conjunction with Western blotting using an anti-gelonin antibody indicated that the polypeptide responsible for DNase activity was gelonin. (jefferson.edu)
  • Chapter Two further characterized the nuclease activity of gelonin and compared it to two other RIPs, pokeweed antiviral protein (PAP) and ricin. (jefferson.edu)
  • Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. (idrblab.net)
  • Analyzing the handoff of DNA from UvrA to UvrB utilizing DNA-protein photoaffinity labeling. (neb.com)
  • Ribosomal protein S3 (RpS3) is involved in protein biosynthesis as a component of the ribosome complex and possesses endonuclease activity to repair damaged DNA. (bmbreports.org)
  • Poly(ADP ribose) polymerase 1 (PARP1) is a multifunctional DNA repair protein of the base excision repair pathway and plays a major role in the repair of DNA strand breaks and in replication and transcriptional regulation among other functions. (nist.gov)
  • More importantly, the results unveil a highly coordinated mechanism by which XRCC1, through its multiple protein-protein interactions, extends its orchestrating role from the base excision step to the resealing of the repaired DNA strand. (nih.gov)
  • The protein is produced by a recombinant E. coli strain carrying the recombinant thermolabile uracil DNA glycosylase gene isolated from a marine bacteria. (qiagen.com)
  • The investigations described in this thesis report two novel findings: (1) the identification of a new class of adenine specific single-stranded DNA glycosylases and (2) the first description of DNA repair activities in Plasmodium falciparum, the protozoan parasite that causes human malaria. (jefferson.edu)
  • It is likely that this pathway utilized a flap endonuclease to process the single-stranded DNA that occurs during repair synthesis. (jefferson.edu)
  • Synthesis, characterization, and application in photoaffinity modification of DNA binding proteins. (neb.com)
  • Comparison of functional properties of mammalian DNA polymerase lambda and DNA polymerase beta in reactions of DNA synthesis related to DNA repair. (neb.com)
  • Low-temperature setup at 50°C of the cDNA synthesis step causes delayed C q values because the newly amplified DNA containing dUTP is cleaved by UDG. (qiagen.com)
  • Non-chelating p-phenylidene-linked bis-imidazoline analogs of known influenza virus endonuclease inhibitors: Synthesis and anti -influenza activity. (bross-medical.com)
  • This prevents strand separation for DNA synthesis or transcription. (savedelicious.com)
  • These actions block DNA synthesis, causing a block at G2 phase and subsequently apoptotic cell death. (savedelicious.com)
  • its N-terminal region is involved in redox activity and regulates multiple transcription factors, and its C-terminus is involved in base excision DNA repair activity. (mediredox.com)
  • Involved in base excision repair of DNA damaged by oxidation or by mutagenic agents. (expasy.org)
  • The sequence of processes undertaken by the enzymes to fix DNA damage is known as "base excision repair" (BER). (phys.org)
  • XRCC1 participates in DNA single strand break and base excision repair (BER) to preserve genetic stability in mammalian cells. (nih.gov)
  • Oxidative stress is a principal cause of DNA damage, and mechanisms to repair this damage are among the most highly conserved of biological processes. (rcsb.org)
  • Base damage and topoisomerase I (Top1)-linked DNA breaks are abundant forms of endogenous DNA breakage, contributing to hereditary ataxia and underlying the cytotoxicity of a wide range of anti-cancer agents. (whiterose.ac.uk)
  • Although inhibition of PARP activity does not sensitize TDP1-deficient cells to Top1 poisons, it confers increased sensitivity to alkylation damage, highlighting partially overlapping roles for PARP and TDP1 in response to genotoxic challenge. (whiterose.ac.uk)
  • Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. (idrblab.net)
  • Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion. (idrblab.net)
  • Together this study highlights role of AcAPE1 in coordinating potential functional overlap between DNA damage repair activity and transcriptional regulation. (unmc.edu)
  • Oxidative stress and DNA damage in agricultural workers. (cdc.gov)
  • Oxidative stress and DNA damage have been proposed as mechanisms linking pesticide exposure to health effects such as cancer and neurological diseases. (cdc.gov)
  • A pilot study of pesticide applicators and farm workers working in the fruit orchards of Oregon (i.e., apples, pears) was conducted to examine the relationship between organophosphate (OP) pesticide exposure and oxidative stress and DNA damage. (cdc.gov)
  • Cellular DNA damage in agricultural workers was validated using lymphocyte cell cultures. (cdc.gov)
  • DNA damage and oxidative DNA repair were significantly greater in lymphocytes from applicators and farm workers when compared with controls. (cdc.gov)
  • A separate field study showed that DNA damage was also significantly greater (p fungicides in the berry crops in Oregon. (cdc.gov)
  • Markers of oxidative stress (i.e., reactive oxygen species, reduced levels of glutathione) and oxidative DNA damage were also observed in lymphocyte cell cultures treated with an OP. The findings from these in vivo and in vitro studies indicate that pesticides induce oxidative stress and DNA damage in agricultural workers. (cdc.gov)
  • Here we discuss the ATAD5-luciferase assay and expand upon the value of HTS in identifying other potential cancer drugs, focusing on cell-based assays that involve DNA damage or repair pathways. (oncotarget.com)
  • In this manuscript, we discuss the various cell-based HTS assays that have been developed to aid in the discovery of chemotherapeutic agents, focusing on those that exploit the DNA damage response. (oncotarget.com)
  • In many cases the antiproloferation action is caused by damage to DNA, which initiates apoptosis and cell death [4]. (savedelicious.com)
  • Here, we show a significantly increased level of intrahelical 8-oxoG and 8-oxoguanine-DNA glycosylase (OGG1) expression in aged human skeletal muscle compared to that of young individuals. (elsevierpure.com)
  • Together these data suggest that that acetylated form of OGG1, and not OGG1 itself, correlates inversely with the 8-oxoG level in the DNA of human skeletal muscle, and the Ac-OGG1 level is dependent on adaptive cellular responses to physical activity, but is age independent. (elsevierpure.com)
  • Transcription factors (TFs) bind to specific regions of DNA known as transcription factor binding sites (TFBSs) and modulate gene expression by interacting with the transcriptional machinery. (bvsalud.org)
  • As a result, TALE:TF complexes are associated with active chromatin and domain/lineage-specific gene activity. (bvsalud.org)
  • Our findings showed that the presence of the anti-endonuclease ardA gene may explain the decrease in the number of CRISPR-Cas systems in E. faecium , known to deactivate the endonucleases' protective activities and enable the E. faecium genome to be versatile in acquiring mobile genetic elements, including carriers of antimicrobial resistance genes, especially vanB . (bross-medical.com)
  • 1 V(D)J recombination and the activity of genes of interest (using GFP as a reporter of gene expression) can be detected as intracellular fluorescence and are measured simultaneously in the same cell population, at the single cell level. (umassmed.edu)
  • This means that the level of expression of p35 and p39 is going to be related to the activity of the enzyme. (wikipedia.org)
  • Integration with assaying enzyme activity and binding affinity for a variety of substrates reveals for the first time that both endonucleolytic and exonucleolytic cleavage can be understood by an induced space-filling model. (nycu.edu.tw)
  • Docking analysis of low-energy poses of the most active compound (as well as their comparison to the binding of an inactive compound) revealed that these compounds reproduced similar binding components to a known PA endonuclease inhibitor and displayed similar binding pose and desired monodentate metal coordination, as was initially envisioned. (bross-medical.com)
  • Tspm promotes the translation of the SACL genes by counteracting the activity of a cis element in their 5'-leader region that suppresses the translation of the main ORF. (bvsalud.org)
  • Here, we performed a comparative genomic analysis of all available genomes of E. faecalis ( n = 1591) and E. faecium ( n = 1981) and investigated the association between the presence or absence of CRISPR-Cas systems, endonuclease/anti-endonuclease systems and the acquisition of antimicrobial resistance, especially vancomycin resistance genes. (bross-medical.com)
  • The lack of AP endonuclease activity of NExo is shown to be attributable to the presence of a histidine side chain, blocking the abasic ribose-binding site. (rcsb.org)
  • The shaded box illustrates how AID first deaminates C to U, and then uracil-DNA glycosylase removes U, leaving an abasic site. (biomedcentral.com)
  • In all cells, high-fidelity pathways repair DNA to maintain the integrity of the genome. (biomedcentral.com)
  • Lyn, a tyrosine kinase that is activated by double-stranded DNA-damaging agents, is involved in various signaling pathways, such as proliferation, apoptosis, and DNA repair. (bmbreports.org)
  • Cleaves the DNA backbone by beta-delta elimination to generate a single-strand break at the site of the removed base with both 3'- and 5'-phosphates. (expasy.org)
  • It attaches itself to the AP site in damaged DNA and cleaves the double strand of DNA into a single strand by digesting a selective number of bases from the other strand. (phys.org)
  • Using the phi29 DNA amplification system, we found that phi29 DNA polymerase is also able to carry out the extension of the dA:dUMP pair and replicate past uracil. (nih.gov)
  • Additionally, UDG and apurinic-apyrimidinic endonuclease treatment of viral DNA isolated from phi29-infected cells revealed that uracil residues arise in phi29 DNA during replication, probably as a result of misincorporation of dUMP by the phi29 DNA polymerase. (nih.gov)
  • The investigation reported in Chapter Three characterized the repair of uracil mismatches and apurinic/apyrimidinic (AP) sites in DNA by a total cell lysate from P. falciparum. (jefferson.edu)
  • The investigation showed that the lysate was capable of removing uracil from DNA, generating AP sites. (jefferson.edu)
  • One unit is the amount of Thermolabile UDG required to release 1 nmol of uracil from dU-containing DNA in one hour at 37°C. (qiagen.com)
  • If performing high-volume, repetitive assays can benefit from adding Uracil-DNA Glycosylase (UDG) to their workflow to exclude carryover contamination. (qiagen.com)
  • UDG removes uracil from the PCR product so that, in each new reaction, residual products are digested and prevented from amplifying while the actual DNA templates are unaffected. (qiagen.com)
  • Add 0.5 µL UDG (G5020L) to a reaction with uracil-containing DNA substrate (up to 0.1 µg) in a 20 µL total reaction. (qiagen.com)
  • In previous studies, we suggested that this inhibition is likely a defense mechanism developed by phage phi29 to prevent the action of UDG if uracilation occurs in DNA either from deamination of cytosine or the incorporation of dUMP during viral DNA replication. (nih.gov)
  • Apurinic/apyrimidinic (AP) sites are the most frequently formed DNA lesions in the genome. (unmc.edu)
  • Thereafter, Pol I attaches itself to the 3' (3 prime end) of the digested DNA strand and fills the gap. (phys.org)
  • The process of switch recombination is activated and targeted by the transcription of switch (S) regions, guanine-rich, 2-10 kilobase stretches of DNA located just upstream of those constant regions that participate in switch recombination (Figure 1 ). (biomedcentral.com)
  • Submicromolar inhibitors were also evaluated by an in vitro endonuclease activity assay using single-stranded DNA, and the results were in full agreement with data from the competitive AlphaScreen assay. (bross-medical.com)
  • A novel chemotype topologically similar to known influenza virus PA endonuclease inhibitors has been designed. (bross-medical.com)
  • The presence of multiple versions of DNA repair enzymes in a single organism is usually thought to reflect redundancy in activities that are essential for cellular viability. (rcsb.org)
  • DNA may be damaged by cellular metabolism byproducts, such as reactive oxygen species, and ionizing radiation (UV and gamma rays). (phys.org)
  • Despite appreciable effort to understand the anti-influenza activity of flavonoids, there is no clear consensus about their precise mode-of-action at a cellular level. (bross-medical.com)
  • In their paper published in Science Advances , the scientists reported that ExoIII has an affinity for apurinic/apyrimidinic (AP) sites-spots on the DNA double helix where a DNA base is missing-in damaged DNA. (phys.org)
  • Catalysis of the removal of damaged bases by cleaving the N-C1' glycosidic bond between the target damaged DNA base and the deoxyribose sugar. (planteome.org)
  • The reaction releases a free base and leaves an apurinic/apyrimidinic (AP) site. (planteome.org)
  • Here, we report that XRCC1 interacts physically and functionally with hOGG1, the human DNA glycosylase that initiates the repair by BER of the mutagenic oxidized base 8-oxoguanine. (nih.gov)
  • Alkylating agents form carbonium ions, which are highly reactive and interact instantaneously with nucleophilic sites such as N7 of guanine in DNA [8]. (savedelicious.com)
  • We demonstrate here that these two AP endonuclease paralogues have distinct activities in DNA repair: one is a typical Neisserial AP endonuclease (NApe), whereas the other is a specialised 3'-phosphodiesterase Neisserial exonuclease (NExo). (rcsb.org)
  • phosphodiesterase activity on bis-pNPP [Ensembl]. (ntu.edu.sg)
  • Induces a robust stimulatory effect on the 3'-5' exonuclease and 3'-phosphodiesterase, but not apurinic-apyrimidinic (AP) endonuclease, APEX2 activities. (idrblab.net)
  • We have identified and characterised two apurinic/apyrimidinic (AP) endonuclease paralogues in the human pathogen Neisseria meningitidis. (rcsb.org)
  • Somatic hypermutation alters variable region sequence, and switch recombination joins a new constant region (Cγ1) to the expressed variable region, producing an extrachromosomal DNA circle (bottom), which contains the deleted region. (biomedcentral.com)
  • The EOMES promoter is used as a case study for single DNA sequence analysis, revealing potential regulation by the LHX9-FOXP1 complex during embryonic development. (bvsalud.org)