Now showing items 1-20 of 88

    • Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement. 

      Patel, AB; Moore, CM; Greber, BJ; Luo, J; Zukin, SA; Ranish, J; Nogales, E (2019-12-30)
      Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a ...
    • A commercial antibody to the human condensin II subunit NCAPH2 cross-reacts with a SWI/SNF complex component. 

      Cutts, EE; Taylor, GC; Pardo, M; Yu, L; Wills, JC; Choudhary, JS; Vannini, A; Wood, AJ (2021-01-13)
      Condensin complexes compact and disentangle chromosomes in preparation for cell division. Commercially available antibodies raised against condensin subunits have been widely used to characterise their cellular interactome. ...
    • A commercial antibody to the human condensin II subunit NCAPH2 cross-reacts with a SWI/SNF complex component 

      Cutts, E; Taylor, G; Pardo, M; Yu, L; Wills, J; Choudhary, J; Vannini, A; Wood, A (2021-01-13)
      Condensin complexes compact and disentangle chromosomes in preparation for cell division. Commercially available antibodies raised against condensin subunits have been widely used to characterise their cellular interactome. ...
    • Structure of human RNA polymerase III. 

      Ramsay, EP; Abascal-Palacios, G; Daiß, JL; King, H; Gouge, J; Pilsl, M; Beuron, F; Morris, E; Gunkel, P; Engel, C; Vannini, A (2020-12-17)
      In eukaryotes, RNA Polymerase (Pol) III is specialized for the transcription of tRNAs and other short, untranslated RNAs. Pol III is a determinant of cellular growth and lifespan across eukaryotes. Upregulation of Pol III ...
    • Induction of detrimental aneuploidy in basal breast cancer cells treated by MPS1 inhibitors in combination with paclitaxel 

      Anderhub, SJ; Mak, GWY; Faisal, A; Walsh, K; Gurden, M; Day, L; Innocenti, P; Woodward, HL; Westwood, IM; Cheung, K-MJ; Naud, S; Hayes, A; Box, G; de Haven Brandon, A; Valenti, MR; O'Fee, L; Saville, H; Burke, R; van Montfort, RLM; Raynaud, FI; Eccles, SA; Blagg, J; Hoelder, S; Linardopoulos, S (AMER ASSOC CANCER RESEARCH, 2017-07-01)
    • Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13. 

      Alfieri, C; Chang, L; Barford, D (2018-07-04)
      The maintenance of genome stability during mitosis is coordinated by the spindle assembly checkpoint (SAC) through its effector the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex (APC/C, ...
    • Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication. 

      On, KF; Beuron, F; Frith, D; Snijders, AP; Morris, EP; Diffley, JFX (2014-03)
      Eukaryotic DNA replication initiates from multiple replication origins. To ensure each origin fires just once per cell cycle, initiation is divided into two biochemically discrete steps: the Mcm2-7 helicase is first loaded ...
    • Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase. 

      Coster, G; Frigola, J; Beuron, F; Morris, EP; Diffley, JFX (2014-09)
      Loading of the six related Minichromosome Maintenance (MCM) proteins as head-to-head double hexamers during DNA replication origin licensing is crucial for ensuring once-per-cell-cycle DNA replication in eukaryotic cells. ...
    • RET recognition of GDNF-GFRα1 ligand by a composite binding site promotes membrane-proximal self-association. 

      Goodman, KM; Kjær, S; Beuron, F; Knowles, PP; Nawrotek, A; Burns, EM; Purkiss, AG; George, R; Santoro, M; Morris, EP; McDonald, NQ (2014-09-18)
      The RET receptor tyrosine kinase is essential to vertebrate development and implicated in multiple human diseases. RET binds a cell surface bipartite ligand comprising a GDNF family ligand and a GFRα coreceptor, resulting ...
    • Molecular mechanisms of human IRE1 activation through dimerization and ligand binding. 

      Joshi, A; Newbatt, Y; McAndrew, PC; Stubbs, M; Burke, R; Richards, MW; Bhatia, C; Caldwell, JJ; McHardy, T; Collins, I; Bayliss, R (2015-05)
      IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although ...
    • SF3B1 mutations constitute a novel therapeutic target in breast cancer. 

      Maguire, SL; Leonidou, A; Wai, P; Marchiò, C; Ng, CK; Sapino, A; Salomon, A-V; Reis-Filho, JS; Weigelt, B; Natrajan, RC (2015-03)
      Mutations in genes encoding proteins involved in RNA splicing have been found to occur at relatively high frequencies in several tumour types including myelodysplastic syndromes, chronic lymphocytic leukaemia, uveal melanoma, ...
    • Molecular mechanism of APC/C activation by mitotic phosphorylation. 

      Zhang, S; Chang, L; Alfieri, C; Zhang, Z; Yang, J; Maslen, S; Skehel, M; Barford, D (2016-05)
      In eukaryotes, the anaphase-promoting complex (APC/C, also known as the cyclosome) regulates the ubiquitin-dependent proteolysis of specific cell-cycle proteins to coordinate chromosome segregation in mitosis and entry ...
    • Molecular basis of APC/C regulation by the spindle assembly checkpoint. 

      Alfieri, C; Chang, L; Zhang, Z; Yang, J; Maslen, S; Skehel, M; Barford, D (2016-08-10)
      In the dividing eukaryotic cell, the spindle assembly checkpoint (SAC) ensures that each daughter cell inherits an identical set of chromosomes. The SAC coordinates the correct attachment of sister chromatid kinetochores ...
    • A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase. 

      Alfieri, C; Tischer, T; Barford, D (2020-06)
      The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is ...
    • DNA origami-based single-molecule force spectroscopy elucidates RNA Polymerase III pre-initiation complex stability. 

      Kramm, K; Schröder, T; Gouge, J; Vera, AM; Gupta, K; Heiss, FB; Liedl, T; Engel, C; Berger, I; Vannini, A; Tinnefeld, P; Grohmann, D (2020-06-05)
      The TATA-binding protein (TBP) and a transcription factor (TF) IIB-like factor are important constituents of all eukaryotic initiation complexes. The reason for the emergence and strict requirement of the additional ...
    • Hybrid Gene Origination Creates Human-Virus Chimeric Proteins during Infection. 

      Ho, JSY; Angel, M; Ma, Y; Sloan, E; Wang, G; Martinez-Romero, C; Alenquer, M; Roudko, V; Chung, L; Zheng, S; Chang, M; Fstkchyan, Y; Clohisey, S; Dinan, AM; Gibbs, J; Gifford, R; Shen, R; Gu, Q; Irigoyen, N; Campisi, L; Huang, C; Zhao, N; Jones, JD; van Knippenberg, I; Zhu, Z; Moshkina, N; Meyer, L; Noel, J; Peralta, Z; Rezelj, V; Kaake, R; Rosenberg, B; Wang, B; Wei, J; Paessler, S; Wise, HM; Johnson, J; Vannini, A; Amorim, MJ; Baillie, JK; Miraldi, ER; Benner, C; Brierley, I; Digard, P; Łuksza, M; Firth, AE; Krogan, N; Greenbaum, BD; MacLeod, MK; van Bakel, H; Garcìa-Sastre, A; Yewdell, JW; Hutchinson, E; Marazzi, I (2020-06-18)
      RNA viruses are a major human health threat. The life cycles of many highly pathogenic RNA viruses like influenza A virus (IAV) and Lassa virus depends on host mRNA, because viral polymerases cleave 5'-m7G-capped host ...
    • Alternative catalytic residues in the active site of Esco acetyltransferases. 

      Ajam, T; De, I; Petkau, N; Whelan, G; Pena, V; Eichele, G (2020-06-17)
      Cohesin is a protein complex whose core subunits, Smc1, Smc3, Scc1, and SA1/SA2 form a ring-like structure encircling the DNA. Cohesins play a key role in the expression, repair, and segregation of eukaryotic genomes. ...
    • Discovery of Potent, Selective, and Orally Bioavailable Small-Molecule Modulators of the Mediator Complex-Associated Kinases CDK8 and CDK19. 

      Mallinger, A; Schiemann, K; Rink, C; Stieber, F; Calderini, M; Crumpler, S; Stubbs, M; Adeniji-Popoola, O; Poeschke, O; Busch, M; Czodrowski, P; Musil, D; Schwarz, D; Ortiz-Ruiz, M-J; Schneider, R; Thai, C; Valenti, M; de Haven Brandon, A; Burke, R; Workman, P; Dale, T; Wienke, D; Clarke, PA; Esdar, C; Raynaud, FI; Eccles, SA; Rohdich, F; Blagg, J (2016-02)
      The Mediator complex-associated cyclin-dependent kinase CDK8 has been implicated in human disease, particularly in colorectal cancer where it has been reported as a putative oncogene. Here we report the discovery of 109 ...
    • 8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors. 

      Bavetsias, V; Lanigan, RM; Ruda, GF; Atrash, B; McLaughlin, MG; Tumber, A; Mok, NY; Le Bihan, Y-V; Dempster, S; Boxall, KJ; Jeganathan, F; Hatch, SB; Savitsky, P; Velupillai, S; Krojer, T; England, KS; Sejberg, J; Thai, C; Donovan, A; Pal, A; Scozzafava, G; Bennett, JM; Kawamura, A; Johansson, C; Szykowska, A; Gileadi, C; Burgess-Brown, NA; von Delft, F; Oppermann, U; Walters, Z; Shipley, J; Raynaud, FI; Westaway, SM; Prinjha, RK; Fedorov, O; Burke, R; Schofield, CJ; Westwood, IM; Bountra, C; Müller, S; van Montfort, RLM; Brennan, PE; Blagg, J (2016-02)
      We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a ...
    • Structure-Enabled Discovery of a Stapled Peptide Inhibitor to Target the Oncogenic Transcriptional Repressor TLE1. 

      McGrath, S; Tortorici, M; Drouin, L; Solanki, S; Vidler, L; Westwood, I; Gimeson, P; Van Montfort, R; Hoelder, S (2017-07)
      TLE1 is an oncogenic transcriptional co-repressor that exerts its repressive effects through binding of transcription factors. Inhibition of this protein-protein interaction represents a putative cancer target, but no ...