Journal articles: 'Ku complex'

1

Nick McElhinny, Stephanie A., Carey M. Snowden, Joseph McCarville, and Dale A. Ramsden. "Ku Recruits the XRCC4-Ligase IV Complex to DNA Ends." Molecular and Cellular Biology 20, no. 9 (May 1, 2000): 2996–3003. http://dx.doi.org/10.1128/mcb.20.9.2996-3003.2000.

Full text

Abstract:

ABSTRACT Genetic experiments have determined that Ku, XRCC4, and ligase IV are required for repair of double-strand breaks by the end-joining pathway. The last two factors form a tight complex in cells. However, ligase IV is only one of three known mammalian ligases and is intrinsically the least active in intermolecular ligation; thus, the biochemical basis for requiring this ligase has been unclear. We demonstrate here a direct physical interaction between the XRCC4-ligase IV complex and Ku. This interaction is stimulated once Ku binds to DNA ends. Since XRCC4-ligase IV alone has very low DNA binding activity, Ku is required for effective recruitment of this ligase to DNA ends. We further show that this recruitment is critical for efficient end-joining activity in vitro. Preformation of a complex containing Ku and XRCC4-ligase IV increases the initial ligation rate 20-fold, indicating that recruitment of the ligase is an important limiting step in intermolecular ligation. Recruitment by Ku also allows XRCC4-ligase IV to use Ku's high affinity for DNA ends to rapidly locate and ligate ends in an excess of unbroken DNA, a necessity for end joining in cells. These properties are conferred only on ligase IV, because Ku does not similarly interact with the other mammalian ligases. We have therefore defined cell-free conditions that reflect the genetic requirement for ligase IV in cellular end joining and consequently can explain in molecular terms why this factor is required.

APA, Harvard, Vancouver, ISO, and other styles

2

Shadrina, Olga, Andrey Anisenko, and Marina Gottikh. "The Role of DNA Repair Complex DNA-PK in HIV-1 Transcription." Proceedings 50, no. 1 (July 16, 2020): 133. http://dx.doi.org/10.3390/proceedings2020050133.

Full text

Abstract:

The human DNA-dependent protein kinase (DNA-PK), composed of the heterodimeric protein Ku and catalytic subunit DNA-PKcs, is a sensor of double-strand DNA breaks in the non-homologous end-joining DNA repair pathway. The key role of DNA-PK in the post-integrational repair of HIV-1 has been shown. It has also been suggested that DNA-PK can participate in the regulation of HIV transcription, although the mechanism is unclear. To clarify the impact of each DNA-PK subunit on the transcription of HIV-1, HEK 293T cells, in which each of the DNA-PK components was depleted, were transfected with reporter vectors containing firefly luciferase under the control of HIV LTR promoter. We detected a positive influence of both Ku subunits, but not of DNA-PKcs, on the transcription from the HIV promoter. Ku is known to interact with HIV-1 TAR RNA, playing an essential role in viral transcription; nonetheless, the deletion of the TAR-coding region from LTR did not alter the Ku effect. Human small noncoding 7SK RNA participates in HIV-1 transcription. The direct binding of recombinant Ku and in vitro transcribed 7SK RNA was demonstrated using EMSA. In addition, we identified the interactions of endogenous Ku with proteins HEXIM1 and Cdk9 from the 7SK RNP complex. These results suggest that Ku exerts its effects on HIV-1 transcription via interaction with the 7SK RNP complex. However, we cannot rule out an indirect effect of Ku on transcription via the regulation of the levels of some transcription factors participating in HIV-1 transcription. We performed a transcriptome analysis of wild type HEK 293T cells and those with depleted DNA-PK subunits. The genes regulated by each subunit were defined and the genes that were mainly dependent on Ku subunits were selected. Among them, we identified transcription factors enhancing HIV-1 transcription, whose levels were downregulated in Ku-depleted cells. The study was supported by RFBR grant №18-04-00542 and RSF grant №17-14-01107.

APA, Harvard, Vancouver, ISO, and other styles

3

Reeves, W. H., A. Pierani, C. H. Chou, T. Ng, C. Nicastri, R. G. Roeder, and Z. M. Sthoeger. "Epitopes of the p70 and p80 (Ku) lupus autoantigens." Journal of Immunology 146, no. 8 (April 15, 1991): 2678–86. http://dx.doi.org/10.4049/jimmunol.146.8.2678.

Full text

Abstract:

Abstract High titer autoantibodies to the Ku Ag, a DNA-protein complex containing 70- and approximately 80-kDa protein subunits (p70 and p80, respectively), are found in sera of certain patients with systemic lupus erythematosus and related disorders. Autoepitopes of the Ku Ag were identified and partially characterized by expressing fragments of the p70 and p80 cDNA as fusion proteins in bacteria. Systemic lupus erythematosus sera reacted on immunoblots with at least three epitopes of p70 (amino acids 560-609, 506-535, and 115-467), and three epitopes of p80 (amino acids 682-732, 558-681, and 1-374). These six antigenic regions had distinct amino acid sequences, and were also immunologically distinct, as determined by using immunoaffinity-purified auto-antibodies to particular epitopes. Detailed mapping of the strongly antigenic region near the C terminus of p70 revealed a complex conformational or discontinuous epitope, the antigenicity of which was abolished by deleting either amino acids 560-571 or 601-609. The C terminus of p80 may also contain a discontinuous or conformational epitope(s). Although only some sera reacted with p70 or p80 on immunoblots, all sera that immunoprecipitated the native Ku complex reacted with native Ku by ELISA, and inhibited the binding of mAb directed at epitopes of native Ku. Taken together, these studies indicate that anti-Ku autoantibodies target a diversity of independent epitopes located on p70, p80, and the intact Ku complex, and that a significant portion of the autoantibodies in most patients' sera is directed against conformational/discontinuous epitopes.

APA, Harvard, Vancouver, ISO, and other styles

4

Koike, M., T. Awaji, M. Kataoka, G. Tsujimoto, T. Kartasova, A. Koike, and T. Shiomi. "Differential subcellular localization of DNA-dependent protein kinase components Ku and DNA-PKcs during mitosis." Journal of Cell Science 112, no. 22 (November 15, 1999): 4031–39. http://dx.doi.org/10.1242/jcs.112.22.4031.

Full text

Abstract:

The Ku protein is a complex of two subunits, Ku70 and Ku80. Ku plays an important role in DNA-PKcs-dependent double-strand break repair and V(D)J recombination, and in growth regulation, which is DNA-PKcs-independent. We studied the expression and the subcellular localization of Ku and DNA-PKcs throughout the cell cycle in several established human cell lines. Using immunofluorescence analysis and confocal laser scanning microscopy, we detected Ku70 and Ku80 in the nuclei in interphase cells. In mitotic cells (1) most of Ku protein was found diffused in the cytoplasm, (2) a fraction was detected at the periphery of condensed chromosomes, (3) no Ku protein was present in the chromosome interior. Association of Ku with isolated chromosomes was also observed. On the other hand, DNA-PKcs was detected in the nucleus in interphase cells and not at the periphery of condensed chromosomes during mitosis. Using indirect immunoprecipitation, we found that throughout the cell cycle, Ku70 and Ku80 were present as heterodimers, some in complex with DNA-PKcs. Our findings suggest that the localization of Ku at the periphery of metaphase chromosomes might be imperative for a novel function of Ku in the G(2)/M phase, which does not require DNA-PKcs.

APA, Harvard, Vancouver, ISO, and other styles

5

Cooper, Marcus P., Amrita Machwe, David K. Orren, Robert M. Brosh, Dale Ramsden, and Vilhelm A. Bohr. "Ku complex interacts with and stimulates the Werner protein." Genes & Development 14, no. 8 (April 15, 2000): 907–12. http://dx.doi.org/10.1101/gad.14.8.907.

Full text

Abstract:

Werner syndrome (WS) is the hallmark premature aging disorder in which affected humans appear older than their chronological age. The protein WRNp, defective in WS, has helicase function, DNA-dependent ATPase, and exonuclease activity. Although WRNp functions in nucleic acid metabolism, there is little or no information about the pathways or protein interactions in which it participates. Here we identify Ku70 and Ku86 as proteins that interact with WRNp. Although Ku proteins had no effect on ATPase or helicase activity, they strongly stimulated specific exonuclease activity. These results suggest that WRNp and the Ku complex participate in a common DNA metabolic pathway.

APA, Harvard, Vancouver, ISO, and other styles

6

Porges, A. J., T. Ng, and W. H. Reeves. "Antigenic determinants of the Ku (p70/p80) autoantigen are poorly conserved between species." Journal of Immunology 145, no. 12 (December 15, 1990): 4222–28. http://dx.doi.org/10.4049/jimmunol.145.12.4222.

Full text

Abstract:

Abstract The Ku (p70/p80) autoantigen is a DNA-protein complex recognized by sera from certain patients with SLE and related diseases. Although human autoantibodies react with at least eight different epitopes of the human Ku complex, they had little reactivity with rodent Ku Ag on immunoblots. Small amounts of 70- and 80-kDa proteins were immunoprecipitated from murine cell extracts, however, suggesting that the Ku particle is not unique to human cells. This was confirmed by isolating cDNA clones encoding murine Ku Ag by plaque hybridization with a human p70 cDNA probe. The murine p70 cDNA clones had a deduced amino acid sequence 82.9% identical to that of human p70, and comparable amounts of murine and human p70 mRNA were detected in 3T3 and K562 cells, respectively. The poor reactivity of human autoantibodies with murine p70 was attributable to specific amino acid substitutions in an immunodominant conformational epitope located on amino acids 560-609 of human p70. Several amino acids critical for antigenicity of this region were defined by mutagenesis studies. Other conformational epitopes of Ku were also antigenically poorly conserved among species. Species-specific epitopes recognized by lupus autoantibodies are unusual but not unique to Ku. In general, poorly conserved autoepitopes have been conformational, rather than sequential, suggesting that the antigenicity of conformational epitopes may be particularly sensitive to evolutionary change.

APA, Harvard, Vancouver, ISO, and other styles

7

Boubnov, N. V., and D. T. Weaver. "scid cells are deficient in Ku and replication protein A phosphorylation by the DNA-dependent protein kinase." Molecular and Cellular Biology 15, no. 10 (October 1995): 5700–5706. http://dx.doi.org/10.1128/mcb.15.10.5700.

Full text

Abstract:

Cell mutants of the Ku nuclear DNA-binding complex are ionizing radiation sensitive and show V(D)J recombination defects. Ku binds and activates a catalytic subunit of DNA-dependent protein kinase (DNA-PK), although the substrates for DNA-PK are unknown. We found that scid cell extracts were deficient in Ku phosphorylation by DNA-PK. Human chromosome 8-complemented scid cells, containing the human DNA-PK catalytic subunit, restored Ku phosphorylation. Likewise, radiation-induced RPA hyperphosphorylation was not completed in scid cells compared with control or chromosome 8-reconstituted cells. Thus, the inactivity of DNA-PK is likely responsible for the repair and recombination defects in scid cells.

APA, Harvard, Vancouver, ISO, and other styles

8

Milne, G. T., S. Jin, K. B. Shannon, and D. T. Weaver. "Mutations in two Ku homologs define a DNA end-joining repair pathway in Saccharomyces cerevisiae." Molecular and Cellular Biology 16, no. 8 (August 1996): 4189–98. http://dx.doi.org/10.1128/mcb.16.8.4189.

Full text

Abstract:

DNA double-strand break (DSB) repair in mammalian cells is dependent on the Ku DNA binding protein complex. However, the mechanism of Ku-mediated repair is not understood. We discovered a Saccharomyces cerevisiae gene (KU80) that is structurally similar to the 80-kDa mammalian Ku subunit. Ku8O associates with the product of the HDF1 gene, forming the major DNA end-binding complex of yeast cells. DNA end binding was absent in ku80delta, hdf1delta, or ku80delta hdf1delta strains. Antisera specific for epitope tags on Ku80 and Hdf1 were used in supershift and immunodepletion experiments to show that both proteins are directly involved in DNA end binding. In vivo, the efficiency of two DNA end-joining processes were reduced >10-fold in ku8Odelta, hdfldelta, or ku80delta hdf1delta strains: repair of linear plasmid DNA and repair of an HO endonuclease-induced chromosomal DSB. These DNA-joining defects correlated with DNA damage sensitivity, because ku80delta and hdf1delta strains were also sensitive to methylmethane sulfonate (MMS). Ku-dependent repair is distinct from homologous recombination, because deletion of KU80 and HDF1 increased the MMS sensitivity of rad52delta. Interestingly, rad5Odelta, also shown here to be defective in end joining, was epistatic with Ku mutations for MMS repair and end joining. Therefore, Ku and Rad50 participate in an end-joining pathway that is distinct from homologous recombinational repair. Yeast DNA end joining is functionally analogous to DSB repair and V(D)J recombination in mammalian cells.

APA, Harvard, Vancouver, ISO, and other styles

9

Zhang, W. W., and M. Yaneva. "Reduced sulphydryl groups are required for DNA binding of Ku protein." Biochemical Journal 293, no. 3 (August 1, 1993): 769–74. http://dx.doi.org/10.1042/bj2930769.

Full text

Abstract:

The Ku protein, a DNA-binding complex that is composed of two subunits of 70 kDa and of 86 kDa, has been suggested to play a role in gene transcription. The dependence of the in vitro DNA-binding activity of affinity-purified Ku protein on reduced cysteine residues has been studied using sulphydryl-modifying agents. Inhibition of the DNA-binding activity was caused by alkylation with N-ethylmaleimide and by crosslinking with azadicarboxylic acid bis(dimethylamide). Treatment of the protein with a large excess of N-ethylmaleimide after it had bound to DNA did not completely dissociate the complex from the DNA, suggesting that some cysteines may be in direct contact with DNA. Pre-incubation of the protein at 37 degrees C or above caused rapid inactivation of DNA binding. The elevated temperature azadicarboxylic acid bis(dimethylamide) treatments resulted in the formation of a crosslinked product, which was detected by Western blotting. The effects of azadicarboxylic acid bis(dimethylmaleimide) and heat were completely reversible by treatment with a reducing agent, such as dithiothreitol. These results demonstrate that in vitro DNA-binding activity of the Ku protein requires reduced sulphydryl groups. Interestingly, the DNA-binding activity of Ku protein was protected from heat inactivation by the presence of a HeLa cell nuclear extract, suggesting that a nuclear factor or factors may be responsible for the maintenance of the reduced cysteines of the Ku protein in vivo. Thus, the biochemical function of the Ku protein may be regulated through oxidation-reduction of its cysteine residues.

APA, Harvard, Vancouver, ISO, and other styles

10

Boboila, Cristian, Catherine Yan, Duane R. Wesemann, Mila Jankovic, Jing H. Wang, John Manis, Andre Nussenzweig, Michel Nussenzweig, and Frederick W. Alt. "Alternative end-joining catalyzes class switch recombination in the absence of both Ku70 and DNA ligase 4." Journal of Experimental Medicine 207, no. 2 (February 8, 2010): 417–27. http://dx.doi.org/10.1084/jem.20092449.

Full text

Abstract:

The classical nonhomologous end-joining (C-NHEJ) DNA double-strand break (DSB) repair pathway employs the Ku70/80 complex (Ku) for DSB recognition and the XRCC4/DNA ligase 4 (Lig4) complex for ligation. During IgH class switch recombination (CSR) in B lymphocytes, switch (S) region DSBs are joined by C-NHEJ to form junctions either with short microhomologies (MHs; “MH-mediated” joins) or no homologies (“direct” joins). In the absence of XRCC4 or Lig4, substantial CSR occurs via “alternative” end-joining (A-EJ) that generates largely MH-mediated joins. Because upstream C-NHEJ components remain in XRCC4- or Lig4-deficient B cells, residual CSR might be catalyzed by C-NHEJ using a different ligase. To address this, we have assayed for CSR in B cells deficient for Ku70, Ku80, or both Ku70 and Lig4. Ku70- or Ku80-deficient B cells have reduced, but still substantial, CSR. Strikingly, B cells deficient for both Ku plus Lig4 undergo CSR similarly to Ku-deficient B cells, firmly demonstrating that an A-EJ pathway distinct from C-NHEJ can catalyze CSR end-joining. Ku-deficient or Ku- plus Lig4-deficient B cells are also biased toward MH-mediated CSR joins; but, in contrast to XRCC4- or Lig4-deficient B cells, generate substantial numbers of direct CSR joins. Our findings suggest that more than one form of A-EJ can function in CSR.

APA, Harvard, Vancouver, ISO, and other styles

11

Mahajan, Kiran N., Stephanie A. Nick McElhinny, Beverly S. Mitchell, and Dale A. Ramsden. "Association of DNA Polymerase μ (pol μ) with Ku and Ligase IV: Role for pol μ in End-Joining Double-Strand Break Repair." Molecular and Cellular Biology 22, no. 14 (July 15, 2002): 5194–202. http://dx.doi.org/10.1128/mcb.22.14.5194-5202.2002.

Full text

Abstract:

ABSTRACT Mammalian DNA polymerase μ (pol μ) is related to terminal deoxynucleotidyl transferase, but its biological role is not yet clear. We show here that after exposure of cells to ionizing radiation (IR), levels of pol μ protein increase. pol μ also forms discrete nuclear foci after IR, and these foci are largely coincident with IR-induced foci of γH2AX, a previously characterized marker of sites of DNA double-strand breaks. pol μ is thus part of the cellular response to DNA double-strand breaks. pol μ also associates in cell extracts with the nonhomologous end-joining repair factor Ku and requires both Ku and another end-joining factor, XRCC4-ligase IV, to form a stable complex on DNA in vitro. pol μ in turn facilitates both stable recruitment of XRCC4-ligase IV to Ku-bound DNA and ligase IV-dependent end joining. In contrast, the related mammalian DNA polymerase β does not form a complex with Ku and XRCC4-ligase IV and is less effective than pol μ in facilitating joining mediated by these factors. Our data thus support an important role for pol μ in the end-joining pathway for repair of double-strand breaks.

APA, Harvard, Vancouver, ISO, and other styles

12

Liu, Jian, Qun Liu, Haijuan Wang, Chunxiao Li, Tao Wen, Guangyu An, and Haili Qian. "NuRD subunit MTA1 interacts with the DNA non-homologous end joining Ku complex in cancer cells." RSC Advances 8, no. 61 (2018): 35218–25. http://dx.doi.org/10.1039/c8ra06907g.

Full text

APA, Harvard, Vancouver, ISO, and other styles

13

Ono, M., H. Ueki, and J. Donald Capra. "097 Role of Ku antigen in DNA-protein complex formation." Journal of Dermatological Science 10, no. 1 (July 1995): 79. http://dx.doi.org/10.1016/0923-1811(95)93815-i.

Full text

APA, Harvard, Vancouver, ISO, and other styles

14

Kragh, Thomas. "Orientations on 2-vector Bundles and Determinant Gerbes." MATHEMATICA SCANDINAVICA 113, no. 1 (September 1, 2013): 63. http://dx.doi.org/10.7146/math.scand.a-15482.

Full text

Abstract:

In a paper from 2009, a half magnetic monopole was discovered by Ausoni, Dundas, and Rognes. This describes an obstruction to the existence of a continuous map $K(ku) \to B(ku^*)$ with determinant like properties. This magnetic monopole is in fact an obstruction to the existence of a map from $K(ku)$ to $K(\mathsf{Z},3)$, which is a retract of the natural map $K(\mathsf{Z},3) \to K(ku)$; and any sensible definition of determinant like should produce such a retract. In this paper we describe this obstruction precisely using monoidal categories. By a result from 2011 by Baas, Dundas, Richter and Rognes $K(ku)$ classifies 2-vector bundles. We thus define the notion of oriented 2-vector bundles, which removes the obstruction by the magnetic monopole. We use this to define an oriented K-theory of 2-vector bundles with a lift of the natural map from $K(\mathsf{Z},3)$. It is then possible to define a retraction of this map and since $K(\mathsf{Z},3)$ classifies complex gerbes we call this a determinant gerbe map.

APA, Harvard, Vancouver, ISO, and other styles

15

Foley, John F. "Aging and autoimmunity." Science Signaling 14, no. 679 (April 20, 2021): eabj0430. http://dx.doi.org/10.1126/scisignal.abj0430.

Full text

APA, Harvard, Vancouver, ISO, and other styles

16

Du, Jin-Hong, Chao Sun, Shuo Bai, Ge Su, Zhe Ying, and Hui-Ming Cheng. "Microwave Electromagnetic Characteristics of a Microcoiled Carbon Fibers/paraffin Wax Composite in Ku Band." Journal of Materials Research 17, no. 5 (May 2002): 1232–36. http://dx.doi.org/10.1557/jmr.2002.0182.

Full text

Abstract:

The complex relative permittivity ∈γ and permeability μγ of microcoiled carbon fibers (MCCFs) imbedded in paraffin wax were measured at Ku band frequencies (12.4–18 GHz). Both the real and imaginary parts of the complex relative permittivity of the MCCFs/paraffin wax composite decreased with increase of the frequency. The real part of the complex relative permeability of the composite increases with increase of the frequency, and the imaginary part is nonzero and nearly constant over the measured frequency range. The dielectric loss tangent (tan δ∈), the magnetic loss tangent (tan δm), and amplitude attenuation factor (α) were determined as well. On the basis of the experimental results, the MCCFs/paraffin wax composite is mainly a kind of dielectric lossy material with small magnetic loss and diamagnetism in the Ku band.

APA, Harvard, Vancouver, ISO, and other styles

17

Cosgrove, A. J. "Ku complex controls the replication time of DNA in telomere regions." Genes & Development 16, no. 19 (October 1, 2002): 2485–90. http://dx.doi.org/10.1101/gad.231602.

Full text

APA, Harvard, Vancouver, ISO, and other styles

18

Manic, Gwenola, Aurélie Maurin-Marlin, Fanny Laurent, Ilio Vitale, Sylvain Thierry, Olivier Delelis, Philippe Dessen, et al. "Impact of the Ku Complex on HIV-1 Expression and Latency." PLoS ONE 8, no. 7 (July 29, 2013): e69691. http://dx.doi.org/10.1371/journal.pone.0069691.

Full text

APA, Harvard, Vancouver, ISO, and other styles

19

Willis, David M., Arleen P. Loewy, Nichole Charlton-Kachigian, Jian-Su Shao, David M. Ornitz, and Dwight A. Towler. "Regulation ofOsteocalcinGene Expression by a Novel Ku Antigen Transcription Factor Complex." Journal of Biological Chemistry 277, no. 40 (July 26, 2002): 37280–91. http://dx.doi.org/10.1074/jbc.m206482200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

20

Shibata, Atsushi, and Penny A. Jeggo. "Roles for the DNA-PK complex and 53BP1 in protecting ends from resection during DNA double-strand break repair." Journal of Radiation Research 61, no. 5 (August 11, 2020): 718–26. http://dx.doi.org/10.1093/jrr/rraa053.

Full text

Abstract:

Abstract p53-binding protein 1 (53BP1) exerts distinct impacts in different situations involving DNA double-strand break (DSB) rejoining. Here we focus on how 53BP1 impacts upon the repair of ionising radiation-induced DSBs (IR-DSBs) and how it interfaces with Ku, the DNA end-binding component of canonical non-homologous end-joining (c-NHEJ), the major DSB repair pathway in mammalian cells. We delineate three forms of IR-DSB repair: resection-independent c-NHEJ, which rejoins most IR-DSBs with fast kinetics in G1 and G2, and Artemis and resection-dependent c-NHEJ and homologous recombination (HR), which repair IR-DSBs with slow kinetics in G1 and G2 phase, respectively. The fast component of DSB repair after X-ray exposure occurs via c-NHEJ with normal kinetics in the absence of 53BP1. Ku is highly abundant and has avid DNA end-binding capacity which restricts DNA end-resection and promotes resection-independent c-NHEJ at most IR-DSBs. Thus, 53BP1 is largely dispensable for resection-independent c-NHEJ. In contrast, 53BP1 is essential for the process of rejoining IR-DSBs with slow kinetics. This role requires 53BP1’s breast cancer susceptibility gene I (BRCA1) C-terminal (BRCT) 2 domain, persistent ataxia telangiectasia mutated (ATM) activation and potentially relaxation of compacted chromatin at heterochromatic-DSBs. In distinction, 53BP1 inhibits resection-dependent IR-DSB repair in G1 and G2, and this resection-inhibitory function can be counteracted by BRCA1. We discuss a model whereby most IR-DSBs are rapidly repaired by 53BP1-independent and resection-independent c-NHEJ due to the ability of Ku to inhibit resection, but, if delayed, then resection in the presence of Ku is triggered, the 53BP1 barrier comes into force and BRCA1 counteraction is required for resection.

APA, Harvard, Vancouver, ISO, and other styles

21

Hanes, J. A., D. A. Archibald, M. Queen, and E. Farrar. "Constraints from 40Ar/39Ar geochronology on the tectonothermal history of the Kapuskasing uplift in the Canadian Superior Province." Canadian Journal of Earth Sciences 31, no. 7 (July 1, 1994): 1146–71. http://dx.doi.org/10.1139/e94-102.

Full text

Abstract:

The Kapuskasing uplift (KU) in the Superior Province of the Canadian Shield has been interpreted as an oblique cross section through the Archean mid-crust. However, the time of juxtaposition of the granulites of the KU against the lower grade rocks of the Abitibi greenstone belt (AGB) along the Ivanhoe Lake fault zone is problematic. To constrain the postmetamorphic tectonothermal history of the KU, we have conducted 57 40Ar/39Ar step-heating analyses on mineral and rock samples collected in a transect across the southern KU and adjacent AGB. The age spectra record a complex thermal history. Amphiboles from the AGB in the footwall of the Ivanhoe Lake fault zone have ca. 2.66 Ga dates, similar to closure ages for amphiboles from farther east in the AGB. Amphibole dates of 2.46–2.52 Ga from the deepest structural levels of the KU place an upper limit on the time of major uplift of the granulites and their juxtaposition with the AGB. Biotite and muscovite dates from the transect cluster into three age groups. The presence in the deepest structural levels of the KU of biotite with 2.40–2.45 Ga dates indicates that significant uplift (15–20 km or more) of the granulites had occurred by this time. Micas with dates in the 2.25–2.30 Ga range are close to fault zones; these dates may indicate a ca. 2.30 Ga episode of fault reactivation. Feldspar, fault-related whole rocks, and some micas record events post 2.1 Ga. These correspond to the emplacement of mafic and lamprophyric dykes and fault reactivation.

APA, Harvard, Vancouver, ISO, and other styles

22

García-Martínez, Juan M., Jennifer Moran, Rosemary G. Clarke, Alex Gray, Sabina C. Cosulich, Christine M. Chresta, and Dario R. Alessi. "Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR)." Biochemical Journal 421, no. 1 (June 12, 2009): 29–42. http://dx.doi.org/10.1042/bj20090489.

Full text

Abstract:

mTOR (mammalian target of rapamycin) stimulates cell growth by phosphorylating and promoting activation of AGC (protein kinase A/protein kinase G/protein kinase C) family kinases such as Akt (protein kinase B), S6K (p70 ribosomal S6 kinase) and SGK (serum and glucocorticoid protein kinase). mTORC1 (mTOR complex-1) phosphorylates the hydrophobic motif of S6K, whereas mTORC2 phosphorylates the hydrophobic motif of Akt and SGK. In the present paper we describe the small molecule Ku-0063794, which inhibits both mTORC1 and mTORC2 with an IC50 of ∼10 nM, but does not suppress the activity of 76 other protein kinases or seven lipid kinases, including Class 1 PI3Ks (phosphoinositide 3-kinases) at 1000-fold higher concentrations. Ku-0063794 is cell permeant, suppresses activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK (ribosomal S6 kinase), an AGC kinase not regulated by mTOR. Ku-0063794 also inhibited phosphorylation of the T-loop Thr308 residue of Akt phosphorylated by PDK1 (3-phosphoinositide-dependent protein kinase-1). We interpret this as implying phosphorylation of Ser473 promotes phosphorylation of Thr308 and/or induces a conformational change that protects Thr308 from dephosphorylation. In contrast, Ku-0063794 does not affect Thr308 phosphorylation in fibroblasts lacking essential mTORC2 subunits, suggesting that signalling processes have adapted to enable Thr308 phosphorylation to occur in the absence of Ser473 phosphorylation. We found that Ku-0063794 induced a much greater dephosphorylation of the mTORC1 substrate 4E-BP1 (eukaryotic initiation factor 4E-binding protein 1) than rapamycin, even in mTORC2-deficient cells, suggesting a form of mTOR distinct from mTORC1, or mTORC2 phosphorylates 4E-BP1. Ku-0063794 also suppressed cell growth and induced a G1-cell-cycle arrest. Our results indicate that Ku-0063794 will be useful in delineating the physiological roles of mTOR and may have utility in treatment of cancers in which this pathway is inappropriately activated.

APA, Harvard, Vancouver, ISO, and other styles

23

Singleton, B. K., M. I. Torres-Arzayus, S. T. Rottinghaus, G. E. Taccioli, and P. A. Jeggo. "The C Terminus of Ku80 Activates the DNA-Dependent Protein Kinase Catalytic Subunit." Molecular and Cellular Biology 19, no. 5 (May 1, 1999): 3267–77. http://dx.doi.org/10.1128/mcb.19.5.3267.

Full text

Abstract:

ABSTRACT Ku is a heterodimeric protein with double-stranded DNA end-binding activity that operates in the process of nonhomologous end joining. Ku is thought to target the DNA-dependent protein kinase (DNA-PK) complex to the DNA and, when DNA bound, can interact and activate the DNA-PK catalytic subunit (DNA-PKcs). We have carried out a 3′ deletion analysis of Ku80, the larger subunit of Ku, and shown that the C-terminal 178 amino acid residues are dispensable for DNA end-binding activity but are required for efficient interaction of Ku with DNA-PKcs. Cells expressing Ku80 proteins that lack the terminal 178 residues have low DNA-PK activity, are radiation sensitive, and can recombine the signal junctions but not the coding junctions during V(D)J recombination. These cells have therefore acquired the phenotype of mouse SCID cells despite expressing DNA-PKcs protein, suggesting that an interaction between DNA-PKcs and Ku, involving the C-terminal region of Ku80, is required for DNA double-strand break rejoining and coding but not signal joint formation. To gain further insight into important domains in Ku80, we report a point mutational change in Ku80 in the defective xrs-2 cell line. This residue is conserved among species and lies outside of the previously reported Ku70-Ku80 interaction domain. The mutational change nonetheless abrogates the Ku70-Ku80 interaction and DNA end-binding activity.

APA, Harvard, Vancouver, ISO, and other styles

24

Ouhassan, Youssef, Seddik Bri, My Chrif El boubakraoui, and Mohamed Habibi. "Permittivity of SiC ceramic matrix compositesin Ku band." E3S Web of Conferences 229 (2021): 01012. http://dx.doi.org/10.1051/e3sconf/202122901012.

Full text

Abstract:

The objective of this work is to determine the dielectric permittivity of two SiC ceramic matrix composites. These composites are reinforced with NicalonSiCfibers and SCS6SiC fibers (SiCf / SiC) and have different volume fractions. The results obtained show that the dielectric property depends on the volume fraction and the frequency. Composites with high volume fractions have better dielectric properties than others. The values of the real and imaginary part of the complex permittivity decrease with frequency increase in the Ku-band. Moreover, the imaginary part takes negative values.

APA, Harvard, Vancouver, ISO, and other styles

25

Tonboe, Rasmus T., Vishnu Nandan, John Yackel, Stefan Kern, Leif Toudal Pedersen, and Julienne Stroeve. "Simulated Ka- and Ku-band radar altimeter height and freeboard estimation on snow-covered Arctic sea ice." Cryosphere 15, no. 4 (April 13, 2021): 1811–22. http://dx.doi.org/10.5194/tc-15-1811-2021.

Full text

Abstract:

Abstract. Owing to differing and complex snow geophysical properties, radar waves of different wavelengths undergo variable penetration through snow-covered sea ice. However, the mechanisms influencing radar altimeter backscatter from snow-covered sea ice, especially at Ka- and Ku-band frequencies, and the impact on the Ka- and Ku-band radar scattering horizon or the “track point” (i.e. the scattering layer depth detected by the radar re-tracker) are not well understood. In this study, we evaluate the Ka- and Ku-band radar scattering horizon with respect to radar penetration and ice floe buoyancy using a first-order scattering model and the Archimedes principle. The scattering model is forced with snow depth data from the European Space Agency (ESA) climate change initiative (CCI) round-robin data package, in which NASA's Operation IceBridge (OIB) data and climatology are included, and detailed snow geophysical property profiles from the Canadian Arctic. Our simulations demonstrate that the Ka- and Ku-band track point difference is a function of snow depth; however, the simulated track point difference is much smaller than what is reported in the literature from the Ku-band CryoSat-2 and Ka-band SARAL/AltiKa satellite radar altimeter observations. We argue that this discrepancy in the Ka- and Ku-band track point differences is sensitive to ice type and snow depth and its associated geophysical properties. Snow salinity is first increasing the Ka- and Ku-band track point difference when the snow is thin and then decreasing the difference when the snow is thick (>0.1 m). A relationship between the Ku-band radar scattering horizon and snow depth is found. This relationship has implications for (1) the use of snow climatology in the conversion of radar freeboard into sea ice thickness and (2) the impact of variability in measured snow depth on the derived ice thickness. For both (1) and (2), the impact of using a snow climatology versus the actual snow depth is relatively small on the radar freeboard, only raising the radar freeboard by 0.03 times the climatological snow depth plus 0.03 times the real snow depth. The radar freeboard is a function of both radar scattering and floe buoyancy. This study serves to enhance our understanding of microwave interactions towards improved accuracy of snow depth and sea ice thickness retrievals via the combination of the currently operational and ESA's forthcoming Ka- and Ku-band dual-frequency CRISTAL radar altimeter missions.

APA, Harvard, Vancouver, ISO, and other styles

26

Melnikova, Larisa, Harald Biessmann, and Pavel Georgiev. "The Ku Protein Complex Is Involved in Length Regulation of Drosophila Telomeres." Genetics 170, no. 1 (March 21, 2005): 221–35. http://dx.doi.org/10.1534/genetics.104.034538.

Full text

APA, Harvard, Vancouver, ISO, and other styles

27

Li Ying-Le, Huang Ji-Ying, and Wang Ming-Jun. "Investigation of electromagnetic complex scattering for spherical targets in Ku wave band." Acta Physica Sinica 57, no. 12 (2008): 7630. http://dx.doi.org/10.7498/aps.57.7630.

Full text

APA, Harvard, Vancouver, ISO, and other styles

28

Ramalingam, Arivudainambi, George E. Farmer, Thomas Stamato, and George C. Prendergast. "Bin1 Interacts with and Restrains the DNA End-Binding Protein Complex Ku." Cell Cycle 6, no. 15 (August 2007): 1914–18. http://dx.doi.org/10.4161/cc.6.15.4514.

Full text

APA, Harvard, Vancouver, ISO, and other styles

29

Ungar, Lior, Yaniv Harari, Amos Toren, and Martin Kupiec. "Tor Complex 1 Controls Telomere Length by Affecting the Level of Ku." Current Biology 21, no. 24 (December 2011): 2115–20. http://dx.doi.org/10.1016/j.cub.2011.11.024.

Full text

APA, Harvard, Vancouver, ISO, and other styles

30

Ying-le, Li, Huang Ji-ying, Wang Ming-jun, and Gong Shu-hong. "Investigation of Electromagnetic Complex Scattering for Spherical Targets in Ku Wave Band." International Journal of Infrared and Millimeter Waves 29, no. 10 (July 30, 2008): 982–89. http://dx.doi.org/10.1007/s10762-008-9386-1.

Full text

APA, Harvard, Vancouver, ISO, and other styles

31

Ono, Masashi, Philip W. Tucker, and J. Donald Capra. "Ku is a general inhibitor of DNA-protein complex formation and transcription." Molecular Immunology 33, no. 9 (June 1996): 787–96. http://dx.doi.org/10.1016/0161-5890(96)00030-2.

Full text

APA, Harvard, Vancouver, ISO, and other styles

32

Nakazawa, M., MT Mitjavila, N. Debili, N. Casadevall, P. Mayeux, P. Rouyer-Fessard, A. Dubart, PH Romeo, Y. Beuzard, and K. Kishi. "KU 812: a pluripotent human cell line with spontaneous erythroid terminal maturation." Blood 73, no. 7 (May 15, 1989): 2003–13. http://dx.doi.org/10.1182/blood.v73.7.2003.2003.

Full text

Abstract:

Abstract A human leukemic cell line KU 812 was recently established and described as a basophilic cell line. In the present study we show that KU 812 and two of its clones are at least bipotent: in addition to a minor component of basophils, the majority of KU 812 cells belongs to the erythroid cell lineage with a significant percentage (about 15%) of mature hemoglobinized erythroblasts. This terminal differentiation is associated with the synchronized synthesis of the main erythroid proteins, including glycophorins, spectrin beta chain, band 3, and hemoglobin. The predominant hemoglobins are adult, fetal, and Bart's hemoglobin. Adult hemoglobin represented up to 75% of all hemoglobins in the KU 812 F clone in passages containing a high number of mature erythroblasts. Transcripts of all human globin chains were present with ten times less embryonic chain messenger RNA (mRNA) than alpha-, beta- or gamma-chain mRNA. Hemin slightly increased the total hemoglobin production of the cell line, especially gamma-globin chain synthesis, but did not modify the percentage of hemoglobinized cells. Phorbol myristate acetate (PMA) had a complex effect, inducing a proportion of KU 812 cells to adhere to the plastic culture flask. The adherent cell fraction expressed a very low level of specific erythroid proteins, but their ultrastructure was consistent with immature erythroid cells. In contrast, approximately 40% of the nonadherent cells were mature erythroid cells. Cell-sorting experiments showed that this paradoxic effect of PMA is mostly due to cell selection, the more mature cells being unable to adhere. In addition, KU 812 F was found to be sensitive to erythropoietin, which slightly increased its plating efficiency range (from 0% to 50%) in semisolid medium and enhanced hemoglobin accumulation twofold. In binding experiments using 125I erythropoietin, a single class of high-affinity Epo receptors (Kd: 250 pM) was detected by binding with a density of 205 receptors per cell. The KU 812 cell line is therefore a unique model for studying cell commitment toward different hematopoietic lineages and erythroid differentiation.

APA, Harvard, Vancouver, ISO, and other styles

33

Nakazawa, M., MT Mitjavila, N. Debili, N. Casadevall, P. Mayeux, P. Rouyer-Fessard, A. Dubart, PH Romeo, Y. Beuzard, and K. Kishi. "KU 812: a pluripotent human cell line with spontaneous erythroid terminal maturation." Blood 73, no. 7 (May 15, 1989): 2003–13. http://dx.doi.org/10.1182/blood.v73.7.2003.bloodjournal7372003.

Full text

Abstract:

A human leukemic cell line KU 812 was recently established and described as a basophilic cell line. In the present study we show that KU 812 and two of its clones are at least bipotent: in addition to a minor component of basophils, the majority of KU 812 cells belongs to the erythroid cell lineage with a significant percentage (about 15%) of mature hemoglobinized erythroblasts. This terminal differentiation is associated with the synchronized synthesis of the main erythroid proteins, including glycophorins, spectrin beta chain, band 3, and hemoglobin. The predominant hemoglobins are adult, fetal, and Bart's hemoglobin. Adult hemoglobin represented up to 75% of all hemoglobins in the KU 812 F clone in passages containing a high number of mature erythroblasts. Transcripts of all human globin chains were present with ten times less embryonic chain messenger RNA (mRNA) than alpha-, beta- or gamma-chain mRNA. Hemin slightly increased the total hemoglobin production of the cell line, especially gamma-globin chain synthesis, but did not modify the percentage of hemoglobinized cells. Phorbol myristate acetate (PMA) had a complex effect, inducing a proportion of KU 812 cells to adhere to the plastic culture flask. The adherent cell fraction expressed a very low level of specific erythroid proteins, but their ultrastructure was consistent with immature erythroid cells. In contrast, approximately 40% of the nonadherent cells were mature erythroid cells. Cell-sorting experiments showed that this paradoxic effect of PMA is mostly due to cell selection, the more mature cells being unable to adhere. In addition, KU 812 F was found to be sensitive to erythropoietin, which slightly increased its plating efficiency range (from 0% to 50%) in semisolid medium and enhanced hemoglobin accumulation twofold. In binding experiments using 125I erythropoietin, a single class of high-affinity Epo receptors (Kd: 250 pM) was detected by binding with a density of 205 receptors per cell. The KU 812 cell line is therefore a unique model for studying cell commitment toward different hematopoietic lineages and erythroid differentiation.

APA, Harvard, Vancouver, ISO, and other styles

34

Lian, Hui-Yong, E. Douglas Robertson, Shin-ichiro Hiraga, Gina M. Alvino, David Collingwood, Heather J. McCune, Akila Sridhar, Bonita J. Brewer, M. K. Raghuraman, and Anne D. Donaldson. "The effect of Ku on telomere replication time is mediated by telomere length but is independent of histone tail acetylation." Molecular Biology of the Cell 22, no. 10 (May 15, 2011): 1753–65. http://dx.doi.org/10.1091/mbc.e10-06-0549.

Full text

Abstract:

DNA replication in Saccharomyces cerevisiae proceeds according to a temporal program. We have investigated the role of the telomere-binding Ku complex in specifying late replication of telomere-proximal sequences. Genome-wide analysis shows that regions extending up to 80 kb from telomeres replicate abnormally early in a yku70 mutant. We find that Ku does not appear to regulate replication time by binding replication origins directly, nor is its effect on telomere replication timing mediated by histone tail acetylation. We show that Ku instead regulates replication timing through its effect on telomere length, because deletion of the telomerase regulator Pif1 largely reverses the short telomere defect of a yku70 mutant and simultaneously rescues its replication timing defect. Consistent with this conclusion, deleting the genome integrity component Elg1 partially rescued both length and replication timing of yku70 telomeres. Telomere length–mediated control of replication timing requires the TG1–3 repeat-counting component Rif1, because a rif1 mutant replicates telomeric regions early, despite having extended TG1–3 tracts. Overall, our results suggest that the effect of Ku on telomere replication timing results from its impact on TG1–3 repeat length and support a model in which Rif1 measures telomere repeat length to ensure that telomere replication timing is correctly programmed.

APA, Harvard, Vancouver, ISO, and other styles

35

Sales, Ana H., Vincent Zheng, Maya A. Kenawy, Mark Kakembo, Lu Zhang, Vladimir Shafirovich, Suse Broyde, and Nicholas E. Geacintov. "Inhibition of E. coli RecQ Helicase Activity by Structurally Distinct DNA Lesions: Structure—Function Relationships." International Journal of Molecular Sciences 23, no. 24 (December 9, 2022): 15654. http://dx.doi.org/10.3390/ijms232415654.

Full text

Abstract:

DNA helicase unwinding activity can be inhibited by small molecules and by covalently bound DNA lesions. Little is known about the relationships between the structural features of DNA lesions and their impact on unwinding rates and processivities. Employing E.coli RecQ helicase as a model system, and various conformationally defined DNA lesions, the unwinding rate constants kobs = kU + kD, and processivities P = (kU/(kU + kD) were determined (kU, unwinding rate constant; kD, helicase-DNA dissociation rate constant). The highest kobs values were observed in the case of intercalated benzo[a]pyrene (BP)-derived adenine adducts, while kobs values of guanine adducts with minor groove or base-displaced intercalated adduct conformations were ~10–20 times smaller. Full unwinding was observed in each case with the processivity P = 1.0 (100% unwinding). The kobs values of the non-bulky lesions T(6−4)T, CPD cyclobutane thymine dimers, and a guanine oxidation product, spiroiminodihydantoin (Sp), are up to 20 times greater than some of the bulky adduct values; their unwinding efficiencies are strongly inhibited with processivities P = 0.11 (CPD), 0.062 (T(6−4)T), and 0.63 (Sp). These latter observations can be accounted for by correlated decreases in unwinding rate constants and enhancements in the helicase DNA complex dissociation rate constants.

APA, Harvard, Vancouver, ISO, and other styles

36

Pawar, Rani, Ninad Velhal, and Vijaya Puri. "Electromagnetic characterization of microwave sintered Sr1-xCaxMnO3 (0.0 ≤ x ≤ 0.4) thick films." Processing and Application of Ceramics 7, no. 1 (2013): 1–7. http://dx.doi.org/10.2298/pac1301001p.

Full text

Abstract:

Electromagnetic characteristics of microwave sintered strontium calcium manganites thick film with variation in calcium content have been investigated. The X-ray diffraction analysis reveals tetragonal perovskite structure for all the compositions. The grain size increases with the increase in calcium content. The microwave absorption, complex permittivity, permeability and conductivity are reported in the frequency range of 8.2-18 GHz. The absorption loss is larger in Ku band while insertion loss is larger in X band. The permittivity, permeability and microwave conductivity decreases from X-band to Ku-band. The almost identical values of real part of permittivity and permeability indicate possible application as materials for impedance matching.

APA, Harvard, Vancouver, ISO, and other styles

37

Ouhassan, Youssef, Seddik Bri, Boubakraoui el, and Mohamed Habibi. "Dielectric properties of ceramic composite materials based on alumina reinforced by titanium carbide." FME Transactions 48, no. 4 (2020): 908–13. http://dx.doi.org/10.5937/fme2004908o.

Full text

Abstract:

The aim of this research work is to study the dielectric and microwave properties of the three ceramic composites Al2O3-TiC, Al2O3-0.3TiC and Al2O3-0.7TiC. The results obtained show that the effective permittivity increases with the increase in the filling rate of titanium carbide TiC inclusions and their contrasts. As for the classical mixing laws, they make it possible to estimate permittivity for low volume fractions and low contrasts. The values of the real part of the complex permittivity decrease with frequency increase in the two bands X and Ku, while the imaginary part is approximately constant in the X band and takes negative values in the Ku band.

APA, Harvard, Vancouver, ISO, and other styles

38

Stankova, Katia, Katia Ivanova, Emil Mladenov, Bustanur Rosidi, Aparna Sharma, Rayna Boteva, and George Iliakis. "Conformational transitions of proteins engaged in DNA double-strand break repair, analysed by tryptophan fluorescence emission and FRET." Biochemical Journal 443, no. 3 (April 16, 2012): 701–9. http://dx.doi.org/10.1042/bj20112151.

Full text

Abstract:

We analysed protein–DNA and protein–protein interactions relevant to the repair of DNA DSBs (double-strand breaks) by NHEJ (non-homologous end-joining). Conformational transitions in mammalian DNA ligases III (LigIII) and IV (LigIV), as well as in PARP-1 [poly(ADP-ribose) polymerase-1], were analysed upon binding to double-stranded DNA by changes in tryptophan emission and FRET (Förster resonance energy transfer) from tryptophan to DNA-conjugated Alexa Fluor® 532. For LigIII, two non-equivalent high- and low-affinity DNA-binding sites are detected interacting sequentially with DNA. PARP-1 displays a single high-affinity DNA-binding site and can displace bound DNA fragments from the low-affinity site of LigIII, consistent with its mediator role in LigIII–DNA interactions. For the LX [LigIV–XRCC4 (X-ray cross-complementation group 4)] complex, a single DNA-binding site is detected. Binding of Ku to DNA was accompanied by conformational changes in the protein and intermolecular FRET from dansyl chromophores of the labelled Ku to the Alexa Fluor® chromophores of Alexa Fluor® 532-conjugated DNA. The average distance of 5.7 nm calculated from FRET data is consistent with a location of Ku at the very end of the DNA molecule. Binding of LX to Ku–DNA complexes is associated with conformational changes in Ku, translocating the protein further towards the DNA ends. The protein–protein and protein–DNA interactions detected and analysed generate a framework for the characterization of molecular interactions fundamental to the function of NHEJ pathways in higher eukaryotes.

APA, Harvard, Vancouver, ISO, and other styles

39

West, Robert B., Mariana Yaneva, and Michael R. Lieber. "Productive and Nonproductive Complexes of Ku and DNA-Dependent Protein Kinase at DNA Termini." Molecular and Cellular Biology 18, no. 10 (October 1, 1998): 5908–20. http://dx.doi.org/10.1128/mcb.18.10.5908.

Full text

Abstract:

ABSTRACT DNA-dependent protein kinase (DNA-PK) is the only eukaryotic protein kinase known to be specifically activated by double-stranded DNA (dsDNA) termini, accounting for its importance in repair of dsDNA breaks and its role in physiologic processes involving dsDNA breaks, such as V(D)J recombination. In this study we conducted kinase and binding analyses using DNA-PK on DNA termini of various lengths in the presence and absence of Ku. We confirmed our previous observations that DNA-PK can bind DNA termini in the absence of Ku, and we determined rate constants for binding. However, in the presence of Ku, DNA-PK can assume either a productive or a nonproductive configuration, depending on the length of the DNA terminus. For dsDNA greater than 26 bp, the productive mode is achieved and Ku increases the affinity of the DNA-PK for the Ku:DNA complex. The change in affinity is achieved by increases in both the kinetic association rate and reduction in the kinetic dissociation rate. For dsDNA smaller than 26 bp, the nonproductive mode, in which DNA-PK is bound to Ku:DNA but is inactive as a kinase, is assumed. Both the productive and nonproductive configurations are likely to be of physiologic importance, depending on the distance of the dsDNA break site to other protein complexes, such as nucleosomes.

APA, Harvard, Vancouver, ISO, and other styles

40

Zahid, Sayma, Murielle Seif El Dahan, Florence Iehl, Paloma Fernandez-Varela, Marie-Helene Le Du, Virginie Ropars, and Jean Baptiste Charbonnier. "The Multifaceted Roles of Ku70/80." International Journal of Molecular Sciences 22, no. 8 (April 16, 2021): 4134. http://dx.doi.org/10.3390/ijms22084134.

Full text

Abstract:

DNA double-strand breaks (DSBs) are accidental lesions generated by various endogenous or exogenous stresses. DSBs are also genetically programmed events during the V(D)J recombination process, meiosis, or other genome rearrangements, and they are intentionally generated to kill cancer during chemo- and radiotherapy. Most DSBs are processed in mammalian cells by the classical nonhomologous end-joining (c-NHEJ) pathway. Understanding the molecular basis of c-NHEJ has major outcomes in several fields, including radiobiology, cancer therapy, immune disease, and genome editing. The heterodimer Ku70/80 (Ku) is a central actor of the c-NHEJ as it rapidly recognizes broken DNA ends in the cell and protects them from nuclease activity. It subsequently recruits many c-NHEJ effectors, including nucleases, polymerases, and the DNA ligase 4 complex. Beyond its DNA repair function, Ku is also involved in several other DNA metabolism processes. Here, we review the structural and functional data on the DNA and RNA recognition properties of Ku implicated in DNA repair and in telomeres maintenance.

APA, Harvard, Vancouver, ISO, and other styles

41

Postow, Lisa, Cristina Ghenoiu, Eileen M. Woo, Andrew N. Krutchinsky, Brian T. Chait, and Hironori Funabiki. "Ku80 removal from DNA through double strand break–induced ubiquitylation." Journal of Cell Biology 182, no. 3 (August 4, 2008): 467–79. http://dx.doi.org/10.1083/jcb.200802146.

Full text

Abstract:

The Ku70/Ku80 heterodimer, or Ku, is the central component of the nonhomologous end joining (NHEJ) pathway of double strand break (DSB) repair. Because Ku forms a ring through which the DSB threads, it likely becomes topologically attached to DNA during repair. The mechanism for its removal was unknown. Using a method to identify proteins recruited to DSBs in Xenopus laevis egg extract, we show that DSB-containing DNAs accumulate members of the Skp1–Cul1–F-box complex and K48-linked polyubiquitylated proteins in addition to known repair proteins. We demonstrate that Ku80 is degraded in response to DSBs in a ubiquitin-mediated manner. Strikingly, K48-linked polyubiquitylation, but not proteasomal degradation, is required for the efficient removal of Ku80 from DNA. This removal is DNA length dependent, as Ku80 is retained on duplex oligonucleotides. Finally, NHEJ completion and removal of Ku80 from DNA are independent from one another. We propose that DSB-induced ubiquitylation of Ku80 provides a mechanism to efficiently eliminate Ku from DNA for pre- and postrepair processes.

APA, Harvard, Vancouver, ISO, and other styles

42

Patterson, Erin E., and Catherine A. Fox. "The Ku Complex in Silencing the Cryptic Mating-Type Loci of Saccharomyces cerevisiae." Genetics 180, no. 2 (August 20, 2008): 771–83. http://dx.doi.org/10.1534/genetics.108.091710.

Full text

APA, Harvard, Vancouver, ISO, and other styles

43

Suwa, A., M. Hirakata, Y. Takeda, S. A. Jesch, T. Mimori, and J. A. Hardin. "DNA-dependent protein kinase (Ku protein-p350 complex) assembles on double-stranded DNA." Proceedings of the National Academy of Sciences 91, no. 15 (July 19, 1994): 6904–8. http://dx.doi.org/10.1073/pnas.91.15.6904.

Full text

APA, Harvard, Vancouver, ISO, and other styles

44

Gepner, David, and Tyler Lawson. "Brauer groups and Galois cohomology of commutative ring spectra." Compositio Mathematica 157, no. 6 (June 2021): 1211–64. http://dx.doi.org/10.1112/s0010437x21007065.

Full text

Abstract:

In this paper we develop methods for classifying Baker, Richter, and Szymik's Azumaya algebras over a commutative ring spectrum, especially in the largely inaccessible case where the ring is nonconnective. We give obstruction-theoretic tools, constructing and classifying these algebras and their automorphisms with Goerss–Hopkins obstruction theory, and give descent-theoretic tools, applying Lurie's work on $\infty$-categories to show that a finite Galois extension of rings in the sense of Rognes becomes a homotopy fixed-point equivalence on Brauer spaces. For even-periodic ring spectra $E$, we find that the ‘algebraic’ Azumaya algebras whose coefficient ring is projective are governed by the Brauer–Wall group of $\pi _0(E)$, recovering a result of Baker, Richter, and Szymik. This allows us to calculate many examples. For example, we find that the algebraic Azumaya algebras over Lubin–Tate spectra have either four or two Morita equivalence classes, depending on whether the prime is odd or even, that all algebraic Azumaya algebras over the complex K-theory spectrum $KU$ are Morita trivial, and that the group of the Morita classes of algebraic Azumaya algebras over the localization $KU[1/2]$ is $\mathbb {Z}/8\times \mathbb {Z}/2$. Using our descent results and an obstruction theory spectral sequence, we also study Azumaya algebras over the real K-theory spectrum $KO$ which become Morita-trivial $KU$-algebras. We show that there exist exactly two Morita equivalence classes of these. The nontrivial Morita equivalence class is realized by an ‘exotic’ $KO$-algebra with the same coefficient ring as $\mathrm {End}_{KO}(KU)$. This requires a careful analysis of what happens in the homotopy fixed-point spectral sequence for the Picard space of $KU$, previously studied by Mathew and Stojanoska.

APA, Harvard, Vancouver, ISO, and other styles

45

Gunes, Cengiz. "Political Representation of Alevi Kurds in Turkey: Historical Trends and Main Transformations." Kurdish Studies 8, no. 1 (May 24, 2020): 71–90. http://dx.doi.org/10.33182/ks.v8i1.522.

Full text

Abstract:

This article explains the process of change in the political representation of Alevi Kurds in Turkey since the country held its first competitive election in 1950. It applies process tracing methodology to identify the dominant trends in Alevi Kurds’ political representation and highlights how the mode of their political participation evolved over time. The discussion presented here develops an explanation that connects the effects of key events and processes that shapes the outcome of this complex political phenomenon. The strong appeal among Alevi Kurds of the Turkish socialist movement and the political parties that are associated with the secular republican regime is discussed before the impact of the rise of Alevi and Kurdish movements on the Alevi Kurds’ political representation is assessed. The barriers Turkey’s restrictive political and legal order place on Alevi Kurds’ political representation are also highlighted. ABSTRACT IN KURMANJI Temsîliyeta siyasî ya kurdên Elewî li Tirkiyeyê: Meylên dîrokî û veguherînên esasî Ev gotar proseya guherîna temsîliyeta siyasî ya kurdên Elewî li Tirkiyeyê, ya ji wexta hilbijartina ewil ya pêşbazîdar a 1950an heta îro, rave dike. Gotar, rêbaza şopandina prosesê tetbîq dike ku meylên serdest ên di temsîliyeta siyasî ya kurdên Elewî de rave bike û li ser disekine ka şêwaza beşdarî û temsîliyeta wan bi demê re çawa vediguhere. Nîqaşa ku li vir hatiye diyarkirin ravekirineke wusa dike ku tesîra bûyerên û proseyên girîng yên ku şikl didin encama vê fenomena sîyasî ya tevlîhev bi hev ve girê dide. Daxwaza xurt a di nav kurdên Elewî yên di nav tevgerên sosyalîst ên tirk û partiyên siyasî yên têkilî rejîma komarî ya sekuler de tê nîqaşkirin berî nirxandina tesîra bilindbûna tevgerên Elewî û kurd ên li ser temsîliyeta siyasî a kurdên Elewî de. Herwiha, bal hatiye kişandin ser astengiyên nîzama qanûnî û siyasî ya sînorker a Tirkiyeyê ya ku li ser temsîliyeta kurdên Elewî bi cih dike.

APA, Harvard, Vancouver, ISO, and other styles

46

Yu, Xin, and Abram Gabriel. "Ku-Dependent and Ku-Independent End-Joining Pathways Lead to Chromosomal Rearrangements During Double-Strand Break Repair inSaccharomyces cerevisiae." Genetics 163, no. 3 (March 1, 2003): 843–56. http://dx.doi.org/10.1093/genetics/163.3.843.

Full text

Abstract:

AbstractChromosomal double-strand breaks (DSBs) can be repaired by either homology-dependent or homology-independent pathways. Nonhomologous repair mechanisms have been relatively less well studied, despite their potential importance in generating chromosomal rearrangements. We have developed a Saccharomyces cerevisiae-based assay to identify and characterize homology-independent chromosomal rearrangements associated with repair of a unique DSB generated within an engineered URA3 gene. Approximately 1% of successfully repaired cells have accompanying chromosomal rearrangements consisting of large insertions, deletions, aberrant gene conversions, or other more complex changes. We have analyzed rearrangements in isogenic wild-type, rad52, yku80, and rad52 yku80 strains, to determine the types of events that occur in the presence or absence of these key repair proteins. Deletions were found in all strain backgrounds, but insertions were dependent upon the presence of Yku80p. A rare RAD52- and YKU80-independent form of deletion was present in all strains. These events were characterized by long one-sided deletions (up to 13 kb) and extensive imperfect overlapping sequences (7-22 bp) at the junctions. Our results demonstrate that the frequency and types of repair events depend on the specific genetic context. This approach can be applied to a number of problems associated with chromosome stability.

APA, Harvard, Vancouver, ISO, and other styles

47

Snaith, Victor. "A Descent Theorem for Hermitian K-Theory." Canadian Journal of Mathematics 39, no. 4 (August 1, 1987): 835–47. http://dx.doi.org/10.4153/cjm-1987-041-5.

Full text

Abstract:

Let KO and KU respectively denote the real and complex periodic K-theory spectra [1, Part III]. Let KSC denote the spectrum representing self-conjugate K-theory [2, G]. Thus we have a fibring1.1where T is induced by complex conjugation on the unitary group.The following result is due to R. Wood [1, p. 206] and, I believe, to D. W. Anderson.1.2. PROPOSITION. Let generate the stable one-stem. Then there are weak equivalences of spectraa andb

APA, Harvard, Vancouver, ISO, and other styles

48

Tomita, Kazunori, Akira Matsuura, Thomas Caspari, Antony M. Carr, Yufuko Akamatsu, Hiroshi Iwasaki, Ken-ichi Mizuno, et al. "Competition between the Rad50 Complex and the Ku Heterodimer Reveals a Role for Exo1 in Processing Double-Strand Breaks but Not Telomeres." Molecular and Cellular Biology 23, no. 15 (August 1, 2003): 5186–97. http://dx.doi.org/10.1128/mcb.23.15.5186-5197.2003.

Full text

Abstract:

ABSTRACT The Mre11-Rad50-Nbs1(Xrs2) complex and the Ku70-Ku80 heterodimer are thought to compete with each other for binding to DNA ends. To investigate the mechanism underlying this competition, we analyzed both DNA damage sensitivity and telomere overhangs in Schizosaccharomyces pombe rad50-d, rad50-d pku70-d, rad50-d exo1-d, and pku70-d rad50-d exo1-d cells. We found that rad50 exo1 double mutants are more methyl methanesulfonate (MMS) sensitive than the respective single mutants. The MMS sensitivity of rad50-d cells was suppressed by concomitant deletion of pku70+ . However, the MMS sensitivity of the rad50 exo1 double mutant was not suppressed by the deletion of pku70+ . The G-rich overhang at telomere ends in taz1-d cells disappeared upon deletion of rad50+ , but the overhang reappeared following concomitant deletion of pku70+ . Our data suggest that the Rad50 complex can process DSB ends and telomere ends in the presence of the Ku heterodimer. However, the Ku heterodimer inhibits processing of DSB ends and telomere ends by alternative nucleases in the absence of the Rad50-Rad32 protein complex. While we have identified Exo1 as the alternative nuclease targeting DNA break sites, the identity of the nuclease acting on the telomere ends remains elusive.

APA, Harvard, Vancouver, ISO, and other styles

49

Andrews, Brooke J., Jason A. Lehman, and John J. Turchi. "Kinetic Analysis of the Ku-DNA Binding Activity Reveals a Redox-dependent Alteration in Protein Structure That Stimulates Dissociation of the Ku-DNA Complex." Journal of Biological Chemistry 281, no. 19 (March 13, 2006): 13596–603. http://dx.doi.org/10.1074/jbc.m512787200.

Full text

APA, Harvard, Vancouver, ISO, and other styles

50

Gravel, Serge, and Raymund J. Wellinger. "Maintenance of Double-Stranded Telomeric Repeats as the Critical Determinant for Cell Viability in Yeast Cells Lacking Ku." Molecular and Cellular Biology 22, no. 7 (April 1, 2002): 2182–93. http://dx.doi.org/10.1128/mcb.22.7.2182-2193.2002.

Full text

Abstract:

ABSTRACT The Saccharomyces cerevisiae Ku complex, while important for nonhomologous DNA end joining, is also necessary for maintaining wild-type telomere length and a normal chromosomal DNA end structure. Yeast cells lacking Ku can grow at 23°C but are unable to do so at elevated temperatures due to an activation of DNA damage checkpoints. To gain insights into the mechanisms affected by temperature in such strains, we isolated and characterized a new allele of the YKU70 gene, yku70-30ts . By several criteria, the Yku70-30p protein is functional at 23°C and nonfunctional at 37°C. The analyses of telomeric repeat maintenance as well as the terminal DNA end structure in strains harboring this allele alone or in strains with a combination of other mutations affecting telomere maintenance show that the altered DNA end structure in yeast cells lacking Ku is not generated in a telomerase-dependent fashion. Moreover, the single-stranded G-rich DNA on such telomeres is not detected by DNA damage checkpoints to arrest cell growth, provided that there are sufficient double-stranded telomeric repeats present. The results also demonstrate that mutations in genes negatively affecting G-strand synthesis (e.g., RIF1) or C-strand synthesis (e.g., the DNA polymerase α gene) allow for the maintenance of longer telomeric repeat tracts in cells lacking Ku. Finally, extending telomeric repeat tracts in such cells at least temporarily suppresses checkpoint activation and growth defects at higher temperatures. Thus, we hypothesize that an aspect of the coordinated synthesis of double-stranded telomeric repeats is sensitive to elevated temperatures.

APA, Harvard, Vancouver, ISO, and other styles

Journal articles on the topic 'Ku complex'

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles