• DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a member of the phosphatidylinositol 3-kinase related kinase family is a well-known player in repairing DNA double strand break through non-homologous end joining pathway. (molcells.org)
  • DNA-dependent protein kinase catalytic subunit (DNA-PKcs), encoded by PRKDC gene, is a member of the phosphatidylinositol 3-kinase-related kinase (PIKK) family, which also includes the two DNA damage repair proteins, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related protein (ATR). (molcells.org)
  • In case of the ada-alkB operon, and the aidB promoter, the N-terminal domain (AdaNTD) is involved in DNA binding and interacts with the a unit of RNA polymerase, whereas and the methylated C-terminal domain (me-AdaCTD) interacts with the σ70 subunit of RNA polymerase. (wikipedia.org)
  • DNA polymerase epsilon, which is involved in DNA repair and replication, is composed of a large catalytic subunit and a small accessory subunit. (nih.gov)
  • The protein encoded by this gene represents the small subunit (B). Defects in this gene have been linked to colorectal cancer and to combined immunodeficiency. (nih.gov)
  • Mutations/polymorphisms in the 55 kDa subunit of DNA polymerase epsilon in human colorectal cancer. (nih.gov)
  • The solution structure of the amino-terminal domain of human DNA polymerase epsilon subunit B is homologous to C-domains of AAA+ proteins. (nih.gov)
  • Purification, cDNA cloning, and gene mapping of the small subunit of human DNA polymerase epsilon. (nih.gov)
  • Gene expression in benzene-exposed workers by microarray analysis of peripheral mononuclear blood cells: induction and silencing of CYP4F3A and regulation of DNA-dependent protein kinase catalytic subunit in DNA double strand break repair. (cdc.gov)
  • DNA-dependent protein kinase catalytic subunit (DNAPKcs) regulates non-homologous end joining (NHEJ) in DNA double strand break (DSB) repair. (cdc.gov)
  • By recruiting the catalytic subunit of DNA-protein kinase (DNA-PKcs, also known as PRKDC ) and other proteins, Ku enables the repair of DNA DSBs through the non-homologous end joining pathway. (nature.com)
  • We found that DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and mammalian target of rapamycin (mTOR) complex 2 (mTORC2) were both required for UVB-induced Akt Ser-473 phosphorylation in keratinocytes. (biomedcentral.com)
  • MORF4L1 may also participate in the formation of NuA4 related complexes which lack the HTATIP/TIP60 catalytic subunit, but which include the SWI/SNF related protein SRCAP. (novusbio.com)
  • To improve HDR efficiency, we screened six small-molecule inhibitors of DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key protein in the alternative repair pathway of non-homologous end joining (NHEJ), which generates genomic insertions/deletions (INDELs). (stanford.edu)
  • DNA-protein kinase catalytic subunit (DNA-PKcs) also known as DNA-activated kinase is a nuclear 460-470 kD serine threonine kinase involved in double-stranded DNA break repair, VDJ recombination, and transcriptional modulation. (biolegend.com)
  • Ku70/80 forms a complex with the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to form the full DNA-dependent protein kinase, DNA-PK [7]. (termedia.pl)
  • In the long-range synaptic complex, X-ray repair cross-complementing 4 (XRCC4) plus XRCC4-like-factor (XLF) form a flexible bridge and linchpin for DNA ends bound to KU heterodimer (Ku70/80) and DNA-PKcs (DNA-dependent protein kinase catalytic subunit). (escholarship.org)
  • The core NHEJ machinery includes XRCC4, DNA ligase IV and the DNA-dependent protein kinase complex, which consists of the DNA end-binding XRCC5/XRCC6 heterodimer and the catalytic subunit PRKDC. (ptglab.com)
  • Regulatory subunit of serine/threonine-protein phosphatase 4. (cansar.ai)
  • Purpose: DNA-dependent protein kinase catalytic subunit (DNA-PK) is a pleiotropic kinase involved in DNA repair and transcriptional regulation. (usuhs.edu)
  • We show that WRN interacts directly with the catalytic subunit of DNA-PK (DNA-PK CS ), which inhibits both the helicase and exonuclease activities of WRN. (elsevierpure.com)
  • In addition we show that WRN forms a stable complex on DNA with DNA-PK CS and the DNA binding subunit Ku. (elsevierpure.com)
  • ATM is usually a member of phosphoinositide 3-kinase (PI3K)-related protein kinase family, which also includes ataxia telangiectasia and Rad3-related protein (ATR) and catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) [23]. (biomasswars.com)
  • In DNA repair, the Ada regulon is a set of genes whose expression is essential to adaptive response (also known as "Ada response", hence the name), which is triggered in prokaryotic cells by exposure to sub-lethal doses of alkylating agents. (wikipedia.org)
  • The product of ada gene, the Ada protein, is an activator of transcription of all four genes. (wikipedia.org)
  • Therefore, an increase in expression of the adaptive response genes, in parallel with the expression of genes producing endogenous alkylators during the stationary phase, prevents alkylation damage to DNA and mutagenesis. (wikipedia.org)
  • Analyzing 5′-upstream non-protein-encoding regions of the human mitochondrial function-associated genes, we speculate that mitochondrial functions could be recovered or improved at a transcriptional level. (intechopen.com)
  • The class Ib RNR operon in B. anthracis encodes genes for the catalytic NrdE protein, the tyrosyl radical metalloprotein NrdF, and the flavodoxin protein NrdI. (ibecbarcelona.eu)
  • Deletion or mutation of genes coding for Ku70 or Ku80 proteins results in a highly radiosensitive phenotype [10]. (termedia.pl)
  • Aberrations of AR, erythroblast transformation-specific ( ETS ) genes, Tumor protein 53 (TP53), and Phosphatase and tensin homolog (PTEN) occurred in 40%-60% of 150 mCRPC cases in a recent study. (oncologynurseadvisor.com)
  • We list the DNA repair genes and related E3 ligases. (bmbreports.org)
  • The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. (bmbreports.org)
  • DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. (bmbreports.org)
  • In addition, cells can produce more than 300 different protein variants from AARS genes through alternative splicing of their mRNAs or post-translational protein fragmentation. (fascea.pics)
  • Protein-protein interaction network analyses identified 20 hub genes, including PTEN, GSK3B, and SMAD3. (bvsalud.org)
  • Retrospective studies of the survivors of famines, such as those exposed to the Dutch Hunger Winter of 1944-45, have linked exposures around conception to later disease outcomes, some of which correlate with DNA methylation changes at certain genes. (frontiersin.org)
  • The gene, called ATM (ataxia-telangiectasia mutated), is a member of a family of phosphatidylinositol-3-kinase-related genes involved in cell cycle control, intracellular protein transport, and DNA damage response. (medscape.com)
  • Serine/threonine-protein phosphatase 4 (PP4) occurs in different assemblies of the catalytic and one or more regulatory subunits. (cansar.ai)
  • published on the web 30 OctoberINTRODUCTION The important mechanisms that cause a constitutive activation of the PI3KAkt pathway are mutations and overexpression of upstream receptor tyrosine kinases which include erbB family members members, activating mutations of PIK3CA or RAS along with the loss of tumor suppressor protein phosphatase and tensin homolog (PTEN).1 Akt, also referred to as protein kinase B (PKB), consists of three isoforms: PKBAkt1, PKBAkt2 and PKBAkt3. (bet-bromodomain.com)
  • Their catalytic function however depends on heterodimer formation with the non-catalytic family members. (uu.nl)
  • We have previously determined the structure of various domains within this family and characterized how these proteins heterodimerize, how they bind to DNA but the catalytic reaction remains elusive and what determines the preferential heterodimer formation is also not known. (uu.nl)
  • Ku exists as a KU70 (also known as XRCC6 )-KU80 (also known as XRCC5 ) heterodimer that binds the ends of DNA double-strand breaks (DSBs). (nature.com)
  • Ku70/80 is a heterodimer of two polypeptides, Ku70 (encoded by XRCC6) and Ku80 (encoded by XRCC5), that binds to DNA double-strand break (DSB) ends and is necessary for the non-homologous end joining (NHEJ) pathway of DNA repair [6]. (termedia.pl)
  • Ku-DNA binding inhibitors that specifically block the Ku70/80 heterodimer interaction with DNA have been developed [12-14]. (termedia.pl)
  • Activation of DNA-PKcs by UV is dependent on ATR (Ataxia telangiectasia mutated and Rad3 related) kinase and is important for replication stress [ 12 ]. (biomedcentral.com)
  • Ataxia telangiectasia mutated (ATM) serine/threonine protein kinase is at the center of DNA double-strand break (DSB) repair [23]. (biomasswars.com)
  • Bcl2 negatively regulates DNA double strand break repair through non-homologous end-joining pathway. (nature.com)
  • Conserved salt-bridge competition triggered by phosphorylation regulates the protein interactome. (uni-wuerzburg.de)
  • FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)
  • 60 identical and the kinase domains are a lot more than 85 identical.three Catalytically active Akt regulates the function of numerous substrates involved in cell survival, development, proliferation, metabolism and protein synthesis (reviewed in Manning, Cantley4). (bet-bromodomain.com)
  • The preferential repair of O6meG is profitable for eukaryotic cells since in experimental animals treated with alkylating carcinogens this lesion is involved in tumor stimulation. (wikipedia.org)
  • Taken together, these results strongly suggest that DNA-PKcs-mTORC2 association is required for UVB-induced Akt Ser-473 phosphorylation and cell survival, and might be important for tumor cell transformation. (biomedcentral.com)
  • This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. (novusbio.com)
  • It is a tumor suppressor gene, involved in DNA DSB repair through the process of homologous recombination [16]. (termedia.pl)
  • The underlying mechanisms by which DNA-PK promotes aggressive tumor phenotypes are not well understood. (usuhs.edu)
  • Here, unbiased molecular investigation in clinically relevant tumor models reveals novel functions of DNA-PK in cancer. (usuhs.edu)
  • Using [18F]-FAC, a dCK-specific positron emission tomography (PET) probe, we visualized and quantified dCK activation in tumor xenografts after IR, indicating that dCK activation could serve as a biomarker for ATM function and DNA damage response in vivo. (biomasswars.com)
  • The Ada protein activates the transcription of the Ada regulon in two different ways. (wikipedia.org)
  • In contrast to the ada and aidB promoters, the unmethylated form of the Ada protein, as well as methylated form of the AdaNTD, is able to activate the transcription at alkA. (wikipedia.org)
  • We characterize in real time the composition and catalytic state of the initial Escherichia coli transcription-coupled repair (TCR) machinery by using correlative single-molecule methods. (nature.com)
  • Selby, C.P. & Sancar, A. Molecular mechanism of transcription-repair coupling. (nature.com)
  • Selby, C.P. & Sancar, A. Structure and function of transcription-repair coupling factor. (nature.com)
  • Hanawalt, P.C. & Spivak, G. Transcription-coupled DNA repair: two decades of progress and surprises. (nature.com)
  • Park, J.-S., Marr, M.T. & Roberts, J.W. E. coli transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation. (nature.com)
  • Structural basis for bacterial transcription-coupled DNA repair. (nature.com)
  • Assenmacher, N., Wenig, K., Lammens, A. & Hopfner, K.-P. Structural basis for transcription-coupled repair: the N terminus of Mfd resembles UvrB with degenerate ATPase motifs. (nature.com)
  • This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. (novusbio.com)
  • Histone acetylation is required in many cellular processes including transcription, DNA repair, and chromatin assembly. (embl.de)
  • p300/CBP acetylations play regulatory roles in transcription, DNA repair and replication, the cell cycle, p53 turnover, and nuclear import. (enzolifesciences.com)
  • 71 Clusterin is a small heat shock glycoprotein overexpressed in most of the solid tumors, which promotes apoptosis by binding to various molecules such as BAX (BCL2-associated X protein) 72 and signal transducer and activator of transcription (STAT)−1. (oncologynurseadvisor.com)
  • A post-translational modification with SUMO (SUMOylation) can regulate various cellular events such as DNA replication, repair, transcription and cell cycle regulation. (ku.edu)
  • Moreover, it seems that binding of BCL2 to Ku prevents the interaction of Ku with DNA ends and with DNA-PKcs, and so decreases the activity of the DNA-PK complex. (nature.com)
  • Though, SUMOylation can affect a substrates' cellular localization, enzymatic activity, or can mediate protein-protein interaction. (ku.edu)
  • Consistent with the idea that EXO1 functions independently in two separate pathways, we defined a domain of Exo1p required for PRR distinct from those required for interaction with MMR proteins. (yeastgenome.org)
  • Lastly, by using a compound exo1 mutant that was defective for interaction with Mlh1p and deficient for nuclease activity, we provide further evidence that Exo1p plays both structural and catalytic roles during MMR. (yeastgenome.org)
  • There are only a few reports on the expression of Ku70/80 in breast cancers [17-21], but the association of this protein with germline CHEK2 mutations in breast cancer patients is unknown. (termedia.pl)
  • For example XPF forms an obligate heterodimeric complex with ERCC1 but not with other members of the family and functions primarily in the Nucleotide Excision Repair (NER) pathway. (uu.nl)
  • This versatile pathway is able to detect and remove a variety of bulky DNA lesions induced by UV light and environmental carcinogens and thereby maintains genome integrity. (uu.nl)
  • An important lesion bypass mechanism is the highly conserved post-replication repair (PRR) pathway that is composed of error-prone translesion and error-free bypass branches. (yeastgenome.org)
  • In this report, we show EXO1 functions in the MMS2 error-free branch of the PRR pathway independent of the role of EXO1 in DNA mismatch repair (MMR). (yeastgenome.org)
  • The pathway of nucleotidyl transfer reaction by human DNA polymerase eta, a key enzyme in translesion synthesis in human cells was newly visualized using time-resolved protein crystallography by freeze trapping. (nii.ac.jp)
  • have reported that increased DNA-PKcs activity can suppress HR repair in G1 phase of cells through increasing RBX1 protein expression, which prompts the neddylation and activity of cullin 1, a key component of the Skp1-Cullin1-F-box ubiquitin 3 ligase, consequently mediating ubiquitination and degradation of EXO1. (molcells.org)
  • Further processing of the abasic site by AP endonucleases, polymerase I, and ligase then completes the repair. (wikipedia.org)
  • DNA-PKcs is modified by phosphorylation and has been shown to interact with Ku70/Ku80, KIP, DNA-ligase IV, and XRCC4 proteins. (biolegend.com)
  • The covalent attachment of ubiquitin to a target protein is catalyzed by the sequential action of a ubiquitin-activating enzyme (E1), a ubiquitin-conjugating enzyme (E2), and a ubiquitin ligase (E3). (bmbreports.org)
  • the E-value for the DNA_ligase_A_N domain shown below is 8.6e-50. (embl.de)
  • DNA ligase (polydeoxyribonucleotide synthase) is the enzyme that joins two DNA fragments by catalysing the formation of an internucleotide ester bond between phosphate and deoxyribose. (embl.de)
  • There are two forms of DNA ligase, one requires ATP ( EC 6.5.1.1 ), the other NAD ( EC 6.5.1.2 ), the latter being restricted to eubacteria. (embl.de)
  • In human DNA ligase I ( P18858 ), and in Saccharomyces cerevisiae (Baker's yeast) ( P04819 ), this region was necessary for catalysis, and separated from the amino terminus by targeting elements. (embl.de)
  • Inhibition of DNA-PKcs activity via its inhibitor NU7026, a dominant-negative kinase-dead mutation, RNA interference (RNAi) or gene depletion led to the attenuation of UVB-induced Akt Ser-473 phosphorylation. (biomedcentral.com)
  • Significantly, we discovered that DNA-PKcs was associated with SIN1 in cytosol upon UVB radiation, and this complexation appeared required for Akt Ser-473 phosphorylation. (biomedcentral.com)
  • Upon binding two DNA ends, auto-phosphorylation opens DNA-PKcs dimer licensing NHEJ via concerted conformational transformations of XLF-XRCC4, XLF-Ku80, and LigIV BRCT -Ku70 interfaces. (escholarship.org)
  • Finally, we show that WRN is phosphorylated in vitro by DNA-PK and requires DNA-PK for phosphorylation in vivo, and that cells deficient in WRN are mildly sensitive to ionizing radiation. (elsevierpure.com)
  • Perilipin 5 (PLIN5) is a lipid-droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). (uci.edu)
  • Ataxia-telangiectasia-related (ATR) protein kinase is central to the deoxyribonucleic acid (DNA) damage response and homologous recombination, activating a series of phosphorylation cascades, culminating in cell cycle arrest to allow time for deoxyribonucleic acid (DNA) repair. (survivornet.com)
  • RNR is a universal enzyme that provides the four essential deoxyribonucleotides needed for DNA replication and repair. (ibecbarcelona.eu)
  • Whether the Fe-NrdF form only exists in vitro or whether the NrdF protein in B. anthracis is a true cambialistic enzyme that can work with either manganese or iron remains to be established. (ibecbarcelona.eu)
  • OGG1_HUMAN ] DNA repair enzyme that incises DNA at 8-oxoG residues. (proteopedia.org)
  • For some amino acids there are two variants with a separate enzyme for use in protein translation, which takes place in the mitochondria. (fascea.pics)
  • During DNA replication, recombination and DNA repair, double-stranded DNA frequently forms three- or four-way junctions, bubbles, flaps or broken ends with single-stranded extensions. (uu.nl)
  • This gene encodes a nuclear protein that is involved in V(D)J recombination and DNA repair. (tumorportal.org)
  • Here we examine non-homologous end joining (NHEJ) as the primary conserved DNA double-strand break (DSB) repair process in human cells. (escholarship.org)
  • There are at least two pathways for eukaryotes to repair DNA double-strand breaks: homologous recombination and nonhomologous end joining(NHEJ). (ptglab.com)
  • Mammalian cells repair DSBs by homologous recombination and non-homologous end joining, the latter requiring DNA-dependent protein kinase (DNA-PK). (elsevierpure.com)
  • These data suggest that DNA-PK and WRN may function together in DNA metabolism and implicate WRN function in non-homologous end joining. (elsevierpure.com)
  • ATR additionally facilitates homologous recombination repair through modulation of the p53-replication protein A (p53-RPA) complex bound to single-stranded deoxyribonucleic acid (ssDNA) during the DNA repair process. (survivornet.com)
  • Ada has two active methyl acceptor cysteine residues that are required for demethylation of DNA. (wikipedia.org)
  • Solution NMR structure of the NlpC/P60 domain of lipoprotein Spr from Escherichia coli: structural evidence for a novel cysteine peptidase catalytic triad. (rostlab.org)
  • Finally, we found that both DNA-PKcs and SIN1 were associated with apoptosis resistance of UVB radiation, and inhibition of them by NU7026 or genetic depletion significantly enhanced UVB-induced cell death and apoptosis. (biomedcentral.com)
  • High-efficiency transgene integration by homology-directed repair in human primary cells using DNA-PKcs inhibition. (stanford.edu)
  • This review focuses on an up-to-date understanding of the functions of E3 ligases in cancers and debates the perspectives of cancer cells that rely on inhibition or activation of ubiquitylation of target proteins. (bmbreports.org)
  • AlkB, one of the Escherichia coli adaptive response proteins, uses an α ketoglutarate/Fe(II)-dependent mechanism that, by chemical oxidation, removes a variety of alkyl lesions from DNA, thus affording protection of the genome against alkylation. (wikipedia.org)
  • DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. (bmbreports.org)
  • The resulting structure is consistent with the currently accepted catalytic mechanism for the protein. (proteopedia.org)
  • Consequently, the mRNA is degraded by a nonsense mediated decay mechanism, resulting in reduced levels of FECH protein and activity. (nccr-rna-and-disease.ch)
  • Structural biology has played an important role in understanding mechanism of DNA repair or replication enzymes. (nii.ac.jp)
  • The alkA gene encodes a glycosylase that repairs a variety of lesions including N-7-Methylguanine and N-3-Methylpurines and O2-methyl pyrimidines. (wikipedia.org)
  • Checkpoint kinase 2 (CHEK2), a cell cycle checkpoint regulator gene, codes for a kinase protein activated in response to radiation and other agents that cause breaks in the DNA. (termedia.pl)
  • The condensation of eukaryotic DNA in arrays of nucleosomes has a profound effect on gene function. (sdbonline.org)
  • Recent studies have revealed that variants of histone H2A and histone H3 play important roles not only in gene expression but also in the repair of DNA breaks and the assembly of chromosome centromeres. (sdbonline.org)
  • DNA methylation is the most commonly studied epigenetic mark in humans, as it is well recognised as a stable, heritable mark that can affect genome function and influence gene expression. (frontiersin.org)
  • Epigenetic marks are heritable DNA modifications that can influence gene expression without changing the DNA sequence. (frontiersin.org)
  • SCOPe: Structural Classification of Proteins - extended. (berkeley.edu)
  • E3 ligases consist of a large family of more than 600 proteins ( 3 ), and a few E3 ligases have been classified based on their conserved structural domains (e.g. (bmbreports.org)
  • Structural basis of O6-alkylguanine recognition by a bacterial alkyltransferase-like DNA repair protein. (rostlab.org)
  • MARV assembles and buds from the host cell plasma where MARV matrix protein (mVP40) dimers associate with anionic lipids at the plasma membrane inner leaflet and undergo a dynamic and extensive self-oligomerization into the structural matrix layer. (uci.edu)
  • H2A.Z is preferentially crosslinked in vivo to intergenic DNA at the PH05 and GAL1 loci, and this association changes with transcriptional activation. (sdbonline.org)
  • Conclusions: These findings uncovered novel DNA-PK transcriptional regulatory functions and led to the development of a combinatorial therapeutic strategy for patients with advanced prostate cancer, currently being tested in the clinical setting. (usuhs.edu)
  • In contrast to the bacterial enzymes it mainly repairs O6meG, whereas removal of the alkyl adduct from O4meT is much slower and significantly less effective. (wikipedia.org)
  • DEC-205 (CD205), a member of the macrophage mannose receptor protein family, is the prototypic endocytic receptor of dendritic cells, whose ligands include phosphorothioated cytosine-guanosine (CpG) oligonucleotides, a motif often seen in bacterial or viral DNA. (uci.edu)
  • The findings indicate that hydroquinone induces DSBs and induction correlates with elevated levels of DNA-PKcs and NHEJ. (cdc.gov)
  • Overexpression of exogenous BCL2 in a lung cancer cell line that expresses no detectable level of the endogenous protein resulted in decreased DNA DSB repair, as shown by persistent DNA DSBs (shown using pulsed field gel electrophoresis) and γH2AX foci, and increased levels of cytogenetic abnormalities compared with controls after exposure to ionizing radiation (IR). (nature.com)
  • Although on the surface and in terms of oncogenesis these findings make sense, it seems counter-intuitive that a protein capable of increasing cell survival after exposure to DNA-damaging agents would also have the capacity to prevent the repair of DNA DSBs. (nature.com)
  • DNA double-strand breaks (DSBs) are a highly mutagenic and potentially lethal damage that occurs in all organisms. (elsevierpure.com)
  • Lastly, knockdown studies revealed that the depletion of endogenous Akt1 and Akt3, but not Akt2, inhibit clonogenic activity and repair of ionizing radiation (IR)induced DNA DSBs, top to radiosensitization. (bet-bromodomain.com)
  • Together, these information indicate that Akt1 and Akt3, but not Akt2, physically interact with DNAPKcs, as a result stimulating the repair of DSBs and hence safeguarding KRASmut cells against IR. (bet-bromodomain.com)
  • Although originally termed histone acetyltransferases (HATs) for their lysine acetylation activity on histone N-terminal tails, CBP and its paralogue, p300, have been shown to acetylate a variety of non-histone proteins including p53, DNA polymerase β and nuclear import factors. (enzolifesciences.com)
  • Has a beta-lyase activity that nicks DNA 3' to the lesion. (proteopedia.org)
  • it also exhibits endonuclease activity on 5' and 3' overhangs and hairpins when complexed with protein kinase, DNA-activated, catalytic polypeptide. (tumorportal.org)
  • PARP-1 binding to sites of DNA damage results in activation of its catalytic activity and generation of chains of poly (ADP-ribosyl)ated polymers, which serve as docking sites for recruitment of DNA repair proteins. (survivornet.com)
  • M6620 (VX-970) is a potent ATR inhibitor, with half maximal inhibitory concentration (IC(50) of 20 nanomolar and antitumor activity across a broad range of cell lines in combination with DNA damaging agents. (survivornet.com)
  • Preclinical studies show M6620 (VX-970) synergizes with cisplatin to induce DNA damage and antitumor activity. (survivornet.com)
  • The addition of PARP inhibitor veliparib with ATR inhibitor M6620 (VX-970) allows for impairment of DNA repair, the induction of a BRCA null phenotype, and potentiation of the antitumor activity of cisplatin. (survivornet.com)
  • Recently we have implemented an in vitro assay that functionally resembles the DNA repair reaction and assays to study protein-protein and protein-DNA interactions. (uu.nl)
  • We previously used DNA nanomanipulation to obtain a nanomechanical readout of protein-DNA interactions during TCR initiation. (nature.com)
  • Moreover, while there are several DNA-PK inhibitors currently being evaluated in the clinical trials in attempt to increase the efficacy of radiotherapy or chemotherapy, multiple functions and subcellular localization of DNA-PKcs in various types of cells may further complicate the effects at the cellular and organismal level. (molcells.org)
  • Here, we investigated a radioiodinated PARP inhibitor, [ 125 I]KX1, and show drug target specific DNA damage and subsequent killing of BRCA1 and non-BRCA mutant ovarian cancer cells at sub-pharmacological concentrations several orders of magnitude lower than traditional PARP inhibitors. (osti.gov)
  • It has been reported that Ku-DNA binding inhibitors modulate the DNA damage response in response to DNA DSB [11]. (termedia.pl)
  • These inhibitors inhibit NHEJ-catalyzed DSB repair and sensitize in vitro cancer cells to DSB-inducing agents. (termedia.pl)
  • Therefore, Ku-DNA binding inhibitors seem to be a promising anticancer therapeutic strategy in combination with DNA DSB-inducing agents [11]. (termedia.pl)
  • Can be used to study CBP kinetics and regulation, for screening for inhibitors or activators and for radiolabeling of proteins or peptides with, for example [ 3 H]-Acetyl CoA. (enzolifesciences.com)
  • Inhibitors of apoptosis proteins (IAPs), mainly survivin and X-linked inhibitor of apoptosis (XIAP) prevent the processing of procaspase 3 to caspase 3, thereby inhibiting apoptosis. (oncologynurseadvisor.com)
  • Mrr from Escherichia coli K12 is a type IV restriction endonuclease whose role is to recognize and cleave foreign methylated DNA. (uci.edu)
  • Since BCL2, a protein that indirectly inhibits cell apoptosis, is required for certain chemotherapies to work, the absence of BCL2 obscures their uses in prostate cancer. (oncologynurseadvisor.com)
  • Docetaxel, in addition to stabilizing microtubules, also induces apoptosis by downregulating antiapoptotic proteins. (oncologynurseadvisor.com)
  • 70 Mcl1 (myeloid cell leukemia differentiation protein 1) and other members of the BCL family, such as BCL-xl (B-cell lymphoma-extra-large), are also involved in resistance to Interleukin (IL)-6, stromal cell derived factor-1, and cytokine-induced apoptosis. (oncologynurseadvisor.com)
  • UVB-induced complexation between DNA-PKcs and mTORC2 components was also abolished by NU7026 and DNA-PKcs mutation. (biomedcentral.com)
  • DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. (bmbreports.org)
  • Little correlation exists between the level of ATM protein and the type of underlying mutation, clinical phenotype, or radiophenotype. (medscape.com)
  • Since NHEJ is error-prone, induction of DNA-PKcs and NHEJ may contribute to mutagenesis and leukemia by benzene. (cdc.gov)
  • Thestructure reveals a buried autoacetylated lysine residue that we show is alsoacetylated in the Rtt109 protein purified from yeast cells. (embl.de)
  • In yeast and mammalian cells, the catalytic disruption of Topo IIα is reported to induce a delay in mitosis. (ku.edu)
  • These studies elucidate the structure-function relationship of these DNA repair proteins. (uu.nl)
  • However, over recent years evidence has been emerging that BCL2 might have a more sinister function: that it might be involved in inhibiting DNA repair. (nature.com)
  • Xingming Deng and colleagues have evidence that BCL2 can block the function of the DNA repair complex Ku. (nature.com)
  • Post-translational modifications change function of most proteins. (bmbreports.org)
  • Experimental Design: DNA-PK function was modulated using both genetic and pharmacologic methods in a series of in vitro models, in vivo xenografts, and patient-derived explants (PDE), and the impact on the downstream signaling and cellular cancer phenotypes was discerned. (usuhs.edu)
  • Here we highlight some of the latest evidence where DNA-PKcs has been shown to localize not only in the nucleus but also in the cytoplasm, phosphorylating various proteins involved in cellular metabolism and cytokine production. (molcells.org)
  • The NuA4 complex interacts with MYC and the adenovirus E1A protein. (novusbio.com)
  • Recent observations suggest that AidB may bind to double-stranded DNA and take part in its dealkylation. (wikipedia.org)
  • This type of four-way DNA structure at the point of strand exchange has become known as an Hj, and the enzymes that resolve them are referred to as Hj-resolving enzymes. (iucr.org)
  • Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. (bmbreports.org)
  • X-ray scattering reveals disordered linkers and dynamic interfaces in complexes and mechanisms for DNA double-strand break repair impacting cell and cancer biology. (escholarship.org)
  • DNA glycosylase/lyases initiate the repair of damaged nucleobases in the genome by catalyzing excision of aberrant nucleobases and nicking of the lesion-containing DNA strand. (proteopedia.org)
  • Poly (ADP-ribose) polymerase-1 (PARP-1) plays a pivotal role in base-excision repair of single strand breaks formed either due to direct genotoxic stress or during the processing of double strand breaks. (survivornet.com)
  • To our knowledge, the study demonstrated for the first time that benzene and metabolites induce CYP4F3A and DNA-PKcs both in vivo and in vitro. (cdc.gov)
  • Nearly all of these proteins have the unusual property of remaining tightly bound in vitro to the end products of the reaction cascade. (proteopedia.org)
  • and (viii) cotargeting DNA-PK/TORK and AR has cooperative growth inhibitory effects in vitro and in vivo. (usuhs.edu)
  • Given their essential role in protein synthesis, they occur regularly and are unlikely to disappear from a viable genome. (fascea.pics)
  • For example, if the AARS of a pathogen is different enough from that of humans, an antibiotic could be developed that disrupts protein synthesis in the infectious agent. (fascea.pics)
  • 1988. Unscheduled DNA synthesis in rat primary hepatocytes with PS-6 unleaded gasoline, its evaporation residue and a DMSO extract. (cdc.gov)
  • The alkylating agents can introduce methyl or ethyl groups at all of the available nitrogen and oxygen atoms in DNA bases, providing a number of lesions. (wikipedia.org)
  • Both sites can become methylated when Ada protein transfers the methyl group from the appropriate DNA lesions to itself. (wikipedia.org)
  • Replication forks stall at DNA lesions or as a result of an unfavorable replicative environment. (yeastgenome.org)
  • Molecular analysis suggested that Esc2p contributed to silencing in a manner similar to Sir1p and probably helped recruit or stabilize the other Sir proteins, while Htz1p present at HMR assembled a specialized chromatin structure necessary for silencing (Dhillon, 2000). (sdbonline.org)
  • These include chemical modifications of DNA bases, post-translational histone modifications and chromatin structure, and their configuration can be affected by a variety of environmental exposures. (frontiersin.org)
  • Animal models have shown more directly that DNA methylation can be affected by dietary supplements that act as cofactors in one-carbon metabolism, and in humans, methylation at birth has been associated with peri-conceptional micronutrient supplementation. (frontiersin.org)
  • response with DNA metabolism by regulating the salvage of deoxyribonucleosides. (biomasswars.com)
  • The 21.7 kDa MGMT protein is built of amino-acid sequences very similar to those of E. coli alkyltransferases, like Ada. (wikipedia.org)
  • Furthermore, they have specific amino acid binding sites ready to interact with other proteins. (fascea.pics)
  • The amino acid sequence for this part of the protein resembled that of a human cytokine, EMAP II, which recruits circulating immune cells in tissues to promote inflammation. (fascea.pics)
  • Eukaryotic, archaebacterial, viral and some eubacterial DNA ligases are ATP-dependent. (embl.de)
  • EXO1 codes for a Rad2p family member nuclease that has been implicated in a multitude of eukaryotic DNA metabolic pathways that include DNA repair, recombination, replication, and telomere integrity. (yeastgenome.org)
  • As poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1) is overexpressed in various cancer types, and is localized to the nucleus, PARP-1 can be safely targeted with Auger emitters to induce DNA damage in tumors. (osti.gov)
  • This family also incorporates the p300/CBP histone acetyltransferase domain which has different catalytic properties and cofactor regulation to KAT11 (PMID:18568037). (embl.de)
  • The most frequent site of alkylation in DNA is the O 6 position of guanine, which forms cross-links between adjacent strands of DNA, leading to cell death. (aacrjournals.org)
  • Beyond this protective role, Mrr can inflict chromosomal DNA damage that elicits the SOS response in the host cell upon heterologous expression of specific methyltransferases such as M.HhaII, or after exposure to high pressure (HP). (uci.edu)
  • Researchers think combining cisplatin with 2 other drugs could block proteins that support cancer cell growth. (survivornet.com)
  • DeMarini, and Chapter 20, by Rice and cell death determine the size protein in several signal ing path- and Herceg). (who.int)
  • Our results indicate that several dozens of proteins for each cell type, are PE-lipoxidated in HT-22, MLE, and H9c2 cells and M2 macrophages after they were induced to undergo ferroptosis. (cdc.gov)
  • It is thought to be involved in DNA binding and in catalysis. (embl.de)
  • This study has found that Swr1, a Swi2/Snf2-related adenosine triphosphatase, is the catalytic core of a multisubunit, histone-variant exchanger that efficiently replaces conventional histone H2A with histone H2AZ in nucleosome arrays. (sdbonline.org)
  • A beta-hairpin comprising the nuclear localization sequence sustains the self-associated states of nucleosome assembly protein 1. (colorado.edu)
  • Solution NMR structure of the SOS response protein YnzC from Bacillus subtilis. (rostlab.org)