Now showing items 54-73 of 88

    • 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. ...
    • Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. 

      Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; Khan, K; Lampis, A; Eason, K; Huntingford, I; Burke, R; Rata, M; Koh, D-M; Tunariu, N; Collins, D; Hulkki-Wilson, S; Ragulan, C; Spiteri, I; Moorcraft, SY; Chau, I; Rao, S; Watkins, D; Fotiadis, N; Bali, M; Darvish-Damavandi, M; Lote, H; Eltahir, Z; Smyth, EC; Begum, R; Clarke, PA; Hahne, JC; Dowsett, M; de Bono, J; Workman, P; Sadanandam, A; Fassan, M; Sansom, OJ; Eccles, S; Starling, N; Braconi, C; Sottoriva, A; Robinson, SP; Cunningham, D; Valeri, N (2018-02)
      Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ...
    • 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 ...
    • Privileged Structures and Polypharmacology within and between Protein Families. 

      Meyers, J; Chessum, NEA; Ali, S; Mok, NY; Wilding, B; Pasqua, AE; Rowlands, M; Tucker, MJ; Evans, LE; Rye, CS; O'Fee, L; Le Bihan, Y-V; Burke, R; Carter, M; Workman, P; Blagg, J; Brown, N; van Montfort, RLM; Jones, K; Cheeseman, MD (2018-12)
      Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (<b>1</b>) and the ...
    • Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach. 

      Innocenti, P; Woodward, HL; Solanki, S; Naud, S; Westwood, IM; Cronin, N; Hayes, A; Roberts, J; Henley, AT; Baker, R; Faisal, A; Mak, GW-Y; Box, G; Valenti, M; De Haven Brandon, A; O'Fee, L; Saville, H; Schmitt, J; Matijssen, B; Burke, R; van Montfort, RLM; Raynaud, FI; Eccles, SA; Linardopoulos, S; Blagg, J; Hoelder, S (2016-04-07)
      Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily ...
    • RavN is a member of a previously unrecognized group of Legionella pneumophila E3 ubiquitin ligases. 

      Lin, Y-H; Lucas, M; Evans, TR; Abascal-Palacios, G; Doms, AG; Beauchene, NA; Rojas, AL; Hierro, A; Machner, MP (2018-02-07)
      The eukaryotic ubiquitylation machinery catalyzes the covalent attachment of the small protein modifier ubiquitin to cellular target proteins in order to alter their fate. Microbial pathogens exploit this post-translational ...
    • Redox Signaling by the RNA Polymerase III TFIIB-Related Factor Brf2. 

      Gouge, J; Satia, K; Guthertz, N; Widya, M; Thompson, AJ; Cousin, P; Dergai, O; Hernandez, N; Vannini, A (2015-12)
      TFIIB-related factor 2 (Brf2) is a member of the family of TFIIB-like core transcription factors. Brf2 recruits RNA polymerase (Pol) III to type III gene-external promoters, including the U6 spliceosomal RNA and selenocysteine ...
    • Regulation of Protein Interactions by <i>M</i>ps <i>O</i>ne <i>B</i>inder (MOB1) Phosphorylation. 

      Xiong, S; Couzens, AL; Kean, MJ; Mao, DY; Guettler, S; Kurinov, I; Gingras, A-C; Sicheri, F (2017-06)
      MOB1 is a multifunctional protein best characterized for its integrative role in regulating Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. Human MOB1 binds both the upstream kinases ...
    • Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. 

      Mariotti, L; Pollock, K; Guettler, S (2017-12)
      The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled ...
    • Relaxed and active thin filament structures; a new structural basis for the regulatory mechanism. 

      Paul, DM; Squire, JM; Morris, EP (2017-03)
      The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca<sup>2+</sup> using electron microscopy and reference-free single ...
    • 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 ...
    • REVEL: An Ensemble Method for Predicting the Pathogenicity of Rare Missense Variants. 

      Ioannidis, NM; Rothstein, JH; Pejaver, V; Middha, S; McDonnell, SK; Baheti, S; Musolf, A; Li, Q; Holzinger, E; Karyadi, D; Cannon-Albright, LA; Teerlink, CC; Stanford, JL; Isaacs, WB; Xu, J; Cooney, KA; Lange, EM; Schleutker, J; Carpten, JD; Powell, IJ; Cussenot, O; Cancel-Tassin, G; Giles, GG; MacInnis, RJ; Maier, C; Hsieh, C-L; Wiklund, F; Catalona, WJ; Foulkes, WD; Mandal, D; Eeles, RA; Kote-Jarai, Z; Bustamante, CD; Schaid, DJ; Hastie, T; Ostrander, EA; Bailey-Wilson, JE; Radivojac, P; Thibodeau, SN; Whittemore, AS; Sieh, W (2016-10)
      The vast majority of coding variants are rare, and assessment of the contribution of rare variants to complex traits is hampered by low statistical power and limited functional data. Improved methods for predicting the ...
    • RNA polymerase I, bending the rules? 

      Jochem, L; Ramsay, EP; Vannini, A (2017-09)
    • 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, ...
    • Solution NMR assignment of the ARC4 domain of human tankyrase 2. 

      Zaleska, M; Pollock, K; Collins, I; Guettler, S; Pfuhl, M (2019-04)
      Tankyrases are poly(ADP-ribose)polymerases (PARPs) which recognize their substrates via their ankyrin repeat cluster (ARC) domains. The human tankyrases (TNKS/TNKS2) contain five ARCs in their extensive N-terminal region; ...
    • Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release. 

      Felisberto-Rodrigues, C; Thomas, JC; McAndrew, C; Le Bihan, Y-V; Burke, R; Workman, P; van Montfort, RLM (2019-09-13)
      DHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here, we report the biochemical characterisation of full-length human DHX8 and the catalytically ...
    • Structural and functional characterization of the human and yeast TFIIIC complex 

      Jochem, L (2019-11-30)
      TFIIIC is one of the conserved transcription factors required for RNA Polymerase (Pol) III transcription, which transcribes DNA into untranslated RNAs, such as tRNAs. However, TFIIIC's mechanistic role in Pol III regulation ...
    • Structural Basis for a Reciprocal Regulation between SCF and CSN 

      Enchev, RI; Scott, DC; da Fonseca, PCA; Schreiber, A; Monda, JK; Schulman, BA; Peter, M; Morris, EP
    • Structural Basis for Auto-Inhibition of the NDR1 Kinase Domain by an Atypically Long Activation Segment. 

      Xiong, S; Lorenzen, K; Couzens, AL; Templeton, CM; Rajendran, D; Mao, DYL; Juang, Y-C; Chiovitti, D; Kurinov, I; Guettler, S; Gingras, A-C; Sicheri, F (2018-08)
      The human NDR family kinases control diverse aspects of cell growth, and are regulated through phosphorylation and association with scaffolds such as MOB1. Here, we report the crystal structure of the human NDR1 kinase ...
    • Structural basis for translocation by AddAB helicase-nuclease and its arrest at χ sites. 

      Krajewski, WW; Fu, X; Wilkinson, M; Cronin, NB; Dillingham, MS; Wigley, DB (2014-04)
      In bacterial cells, processing of double-stranded DNA breaks for repair by homologous recombination is dependent upon the recombination hotspot sequence χ (Chi) and is catalysed by either an AddAB- or RecBCD-type ...