Ku protein

They demonstrated that Ku is an essential co

Feb 26, 2010 · The repair of DNA double-strand breaks (DSBs) is critical for the maintenance of genomic integrity and viability for all organisms. Mammals have evolved at least two genetically discrete ways to mediate DNA DSB repair: homologous recombination (HR) and non-homologous end joining (NHEJ). Ku is the first protein of the NHEJ repair complex to recognize and bind broken DNA ends, binding within 10 s of a DSB forming [ 180 ]. Ku threads onto both broken ends in a sequence-independent manner, with most models depicting a single heterodimer binding each end [ 1, 20 ].Nov 13, 2020 · with identification of the Ku protein as an autoantigen in sclero-derma-polymyositis overlap syndrome (9, 10). In the hope of gain-ing insight into the pathogenesis of autoimmune disease, Ku was extensively characterized. Ku is a heterodimer of 70 and 86 kDa (Ku70 and Ku86) that binds with strong affinity to DNA ends, stem-loop or bubble struc-

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The Ku protein is the heterodimeric regulatory com-ponent of the serine/threonine kinase, DNA-dependent protein kinase (DNA-PK) [1]. Ku consists of 80 (Ku80) and 70 kDa (Ku70) subunits [2].Biography —. Dr. Scott Lovell has served as Director of the Protein Structure Laboratory (PSXL) at the University of Kansas (KU) since 2008 and has 27 years of experience in the X-ray crystallography field. He received his Ph.D. from Purdue University in chemistry where he was trained in X-ray crystallography and studied the structural and ...The Ku (p70/p80) autoantigen, a heterodimer consisting of 70 kDa (p70) and 80 kDa (p80) protein subunits, is one of a group of DNA-associated autoantigens identified as targets of autoantibodies produced by patients with SLE and related disorders. Many of these DNA-protein antigens are involved in organizing the genome into transcriptionally ...The dissection of the Ku protein from eukaryotes and prokaryotes into individual domains described above suggests an evolutionary scenario for these proteins. The Ku core is an ancient domain that was probably present in bacteria and archea even before the advent of the eukaryotes. There are clear indications that, in these organisms, the Ku ...DNA double-strand breaks (DSBs) are considered most hazardous for the organism and are generally repaired by nonhomologous end joining (NHEJ), where Ku protein acts as the sensor and binds to specific protein kinases, leading to the joining of the broken strands [120].Bacterial Ku is usually found as a single gene and exists as homodimers. It is much smaller than the eukaryotic Ku proteins and does not include the vWA and SAP domains that make Ku 70/80 distinct. These additional domains allow eukaryotic Ku to behave as a scaffold protein and interact with the variety of factors in the more complex NHEJ system. The Ku heterodimer, composed of Ku70 and Ku80, is best characterized for its role in repairing double-stranded DNA breaks but is also known to participate in other regulatory processes. Despite our understanding of Ku protein interplay during DNA repair, the extent of Ku's protein interactions in other processes has never been fully determined.The design of potent inhibitors of Ku-DNA or Ku-protein interactions will be central to characterize new molecules that may serve as a radiosensitizer or to improve genome editing. Acknowledgments. We would like to thank Patrick Calsou (IPBS, Toulouse), Stephane Marcand and Florian Roisné-Hamelin (Institut Jacob, iRCM, Fontenay aux rose), and ...Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of caspase-3, which degrades Ku 70/80. Cells with decreased Ku protein levels undergo apoptosis. Astaxanthin exerts antioxidant activity by inducing the expression of catalase, an antioxidant enzyme, in gastric epithelial cells.Ku protein preparations (4 μg), prepared as stated above, were subjected to limited proteolysis by the addition of 200 ng of sequencing grade bovine trypsin. Reactions were performed in buffer A and incubated at 37°C for10 minutes. Reactions were terminated by the addition of SDS loading dye and samples were separated by SDS-PAGE.May 17, 2017 · DNA-dependent protein kinase catalytic subunit (DNA-PKcs) has a high affinity for Ku–DNA ends and, together with Ku, forms the DNA-PK complex 4 . Figure 1: Overview of non-homologous end joining. The DNA end-binding activity of Ku may also be involved in protection of chromosomal ends from nucleases, as yeast deficient in Ku70 or Ku80 display marked telomere attrition [1, 2]. Ku protein homologues have been identified in vertebrates, insects, Caenorhabditis elegans and yeast but not, to date, in prokaryotes. It is important to ...They demonstrated that Ku is an essential component of DNA-PK, mediating the binding of DNA-PKcs to the dsDNA end . The Ku protein was initially identified by Mimori et al. as the antigen of the autoantibody in a patient of an autoimmune disease, polymyositis–scleroderma overlap .About this page Nonhomologous End Joining in Bacteria E.J. Bartlett, A.J. Doherty, in Encyclopedia of Biological Chemistry (Second Edition), 2013 Bacterial Ku All Ku proteins form dimeric ring-like structures, capable of sliding over DNA ends. Ku does not bind to specific genetic sequences, nor make extensive contacts with the phosphate backbone.A dimeric protein complex called KU initiates this process by binding to the broken DNA ends, then recruiting the DNA-PK catalytic subunit (DNA-PKcs) to form the active DNA-PK enzyme (Fig. 1a).Non-homologous end-joining (NHEJ) is a double strand break (DSB) repair pathway which does not require any homologous template and can ligate two DNA ends together. The basic bacterial NHEJ machinery involves two partners: the Ku protein, a DNA end binding protein for DSB recognition and the multifunctional LigD protein composed a ligase, a nuclease and a polymerase domain, for end processing ...Dec 4, 2020 · Section snippets Yku80 is an in vitro and in vivo substrate of Pho85-Pcl1. In a genome-wide search for protein–protein interaction events in S. cerevisiae, Yku80 was found as a physical interactor to the CDK Pho85. 64 Furthermore, pho85Δ cells are sensitive to hydroxyurea, agent that by inhibiting dNTPs synthesis produces DNA damage 65 …LAWRENCE — Research from the University of Kansas just published in Proceedings of the National Academy of Sciences could hasten development of a new class of vaccines aimed at SARS-CoV-2, the virus that causes COVID-19.. Anthony Fehr, associate professor of molecular biosciences, led research into a protein dubbed "Mac1," which has intrigued molecular bioscientists as an antiviral ...Collectively, our data show that zinc-finger protein ZNF384 is an adapter of Ku to DNA during DSB repair via cNHEJ. Results. ZNF384 is recruited to DNA damage sites and interacts with NHEJ proteins.

The Ku autoantigen is a DNA binding factor consisting of 70 and approximately 80 kDa proteins (p70 and p80, respectively) which form a heterodimer. The p70/p80 dimer appears to be crucial for the function of a 350 kDa DNA-dependent protein kinase (DNA-PK) that phosphorylates certain transcription fa …7 Jun 2023 ... to characterize the DNA binding properties of mycobacterial protein Ku (mKu) and its role in. 39 mycobacterial NHEJ. Here, we report the ...Application Notes: Ku protein is a heterodimer of 2 tightly associated sub-units called the Ku70 and Ku80, normally located in the nucleus, where it is involved in nonhomologous end-joining processes, which is responsible for repairing double stranded DNA breaks. The receptor-mediated endocytosis of Ku70/80 is rapid (t1/2 12 min) and extensive ...Transcriptional reinitiation is a distinct phase of the RNA polymerase II transcription cycle. Prior work has shown that reinitiation is deficient in nuclear extracts from Chinese hamster ovary cells lacking the 80-kDa subunit of Ku, a double-strand break repair protein, and that activity is rescued by expression of the corresponding cDNA. We now show that Ku increases the amount or ...

A select group of proteins, known as the pre-replication (pre-RC) complex, in whose formation the Ku protein (Ku70/Ku86) was shown to play a role, bind to replication origins to initiate DNA replication. In this study, we have examined the involvement of Ku in breast tumorigenesis and tumor progression and found that the Ku protein expression ...Conventionally, KU complex, the regulatory subunit of DNA-dependent protein kinase (DNA-PK), together with the catalytic subunit of DNA-PK (DNA-PKcs), mediates DNA damage repair in the nucleus. Here, we found KU complex abundantly expressed in the cytoplasm, where it recognized accumulated cytoplasmic DNA in aged human and mouse CD4 + T cells ...Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of caspase-3, which degrades Ku 70/80. Cells with decreased Ku protein levels undergo apoptosis. Astaxanthin exerts antioxidant activity by inducing the expression of catalase, an antioxidant enzyme, in gastric epithelial cells.…

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The dissection of the Ku protein from eukaryotes and prokaryotes into individual domains described above suggests an evolutionary scenario for these proteins. The Ku core is an ancient domain that was probably present in bacteria and archea even before the advent of the eukaryotes. There are clear indications that, in these organisms, the Ku ...DNA-PKcs pushes Ku protein inwards onto the DNA, and then phosphorylates the other components nearby, including its own phosphorylation. DNA-PKcs autophosphorylation can be regulated by N-terminal conformational changes of protein (Meek et al., 2012). In addition to the automatic regulation of DNA-PKcs, many other factors are also suggested to ...

Here, small angle X-ray scattering (SAXS) and mutational analyses show APLF is largely an intrinsically disordered protein that binds Ku, Ku/DNA-PKcsmore » X4L4 assembles with Ku heterodimers linked to DNA-PKcs via flexible Ku80 C-terminal regions (Ku80CTR) in a complex stabilized through APLF interactions with Ku, DNA-PK, and X4L4.Ku (protein) and DNA polymerase mu · See more » DNA-PKcs. DNA-dependent protein kinase, catalytic subunit, also known as DNA-PKcs, is an enzyme that in humans is encoded by the gene designated as PRKDC or XRCC7. New!!: Ku (protein) and DNA-PKcs · See more » ETS1. Protein C-ets-1 is a protein that in humans is encoded by the ETS1 gene. New!!:30°C in the presence of 20 nM Ku protein, 18.5 nM DNA-PKcs, 70 µM peptide and 40 µM[γ-32P]ATP (12.5 Ci/mmol) in a total volume of 20 µl. Reactions were stopped by addition of 10 µlof

specificity of Ku for ends and its abili The proteins cover different functional and structural classes, and the aminophilic electrophiles include compounds that disrupt protein–protein and protein–RNA interactions. No Ku protein Chromosome instability No or slow repaThe Ku heterodimer plays a central role in non Ku is a well-known protein heterodimer comprised of 70 and 80 kDa subunits and is best-known for its central role in binding to DNA and the double-strand break DNA repair pathway in mammals.2 There are several challenges when describing the clinical phenotype of patients with anti-Ku antibodies. First, as noted above, Ku is a DNA-binding protein. Subsequent biological screening resulted in the first ident Sep 1, 1999 · The level of Ku protein was assessed by Western blot with anti-Ku antiserum in cytoplasmic, nuclear, and whole-cell extracts from unstimulated or activated B cells. One representative datum from six comparable experiments is shown. (B) Ku fails to associate with CD40 in B cells following stimulation that induces IgCS. Membrane/cytoplasmic ... Ku protein is a heterodimer (Ku70 and Ku8The Protein Structure Laboratory offers a range of servicIn Ku and/or DNA-PKcs-defective cell lines, some DSB re Matthias Mann is Research Director and Group leader at the Proteomics Program at Novo Nordisk Foundation Center for Protein Research (CPR, www.cpr.ku.dk) at the University of Copenhagen. He also holds a Director position at the Max-Planck Institute of Biochemistry in Munich. Matthias Mann is one of the most highly cited researchers in the world ...In addition, Ku is an essential protein in humans probably through telomere stabilization and no stable human Ku knock-out cell line exists, although conditional genetic ablation of Ku80 has been described (39,57). Here, we have engineered models of human cell lines in which the expression of Ku can be significantly lowered by the conditional ... All patients had very high titer of ANA with speckled and n Oxidative stress induces DNA damage which can be repaired by DNA repair proteins, such as Ku70/80. Excess reactive oxygen species (ROS) stimulate the activation of caspase-3, which degrades Ku 70/80. Cells with decreased Ku protein levels undergo apoptosis. Astaxanthin exerts antioxidant activity by inducing the expression of catalase, an antioxidant enzyme, in gastric epithelial cells. Ku protein degradation. In conclusion, dietary astaxanthin supplemen[The Ku protein is a DNA-binding nuclear protein complex cOct 14, 2021 · The Ku protein also has a high affinity Together, these results support the conclusion that the Ku Core domain plays a critical role in mediating the interaction of the Ku protein with cGAS and in augmenting cGAS-DNA binding, resulting in enhanced cGAS condensation and activity. Download : Download high-res image (879KB) Download : Download full-size image; Figure 6.