Now showing items 17-36 of 89

    • 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. ...
    • 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. ...
    • Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation. 

      Jones, M; Beuron, F; Borg, A; Nans, A; Earl, CP; Briggs, DC; Snijders, AP; Bowles, M; Morris, EP; Linch, M; McDonald, NQ (2020-02-28)
      The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated ...
    • Demonstrating In-Cell Target Engagement Using a Pirin Protein Degradation Probe (CCT367766). 

      Chessum, NEA; Sharp, SY; Caldwell, JJ; Pasqua, AE; Wilding, B; Colombano, G; Collins, I; Ozer, B; Richards, M; Rowlands, M; Stubbs, M; Burke, R; McAndrew, PC; Clarke, PA; Workman, P; Cheeseman, MD; Jones, K (2018-02)
      Demonstrating intracellular protein target engagement is an essential step in the development and progression of new chemical probes and potential small molecule therapeutics. However, this can be particularly challenging ...
    • Discovery of a Chemical Probe Bisamide (CCT251236): An Orally Bioavailable Efficacious Pirin Ligand from a Heat Shock Transcription Factor 1 (HSF1) Phenotypic Screen. 

      Cheeseman, MD; Chessum, NEA; Rye, CS; Pasqua, AE; Tucker, MJ; Wilding, B; Evans, LE; Lepri, S; Richards, M; Sharp, SY; Ali, S; Rowlands, M; O'Fee, L; Miah, A; Hayes, A; Henley, AT; Powers, M; Te Poele, R; De Billy, E; Pellegrino, L; Raynaud, F; Burke, R; van Montfort, RLM; Eccles, SA; Workman, P; Jones, K (2017-01)
      Phenotypic screens, which focus on measuring and quantifying discrete cellular changes rather than affinity for individual recombinant proteins, have recently attracted renewed interest as an efficient strategy for drug ...
    • The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design. 

      Couty, S; Westwood, IM; Kalusa, A; Cano, C; Travers, J; Boxall, K; Chow, CL; Burns, S; Schmitt, J; Pickard, L; Barillari, C; McAndrew, PC; Clarke, PA; Linardopoulos, S; Griffin, RJ; Aherne, GW; Raynaud, FI; Workman, P; Jones, K; van Montfort, RLM (2013-10)
      The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we ...
    • 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 ...
    • Dissecting mechanisms of resistance to targeted drug combination therapy in human colorectal cancer. 

      Clarke, PA; Roe, T; Swabey, K; Hobbs, SM; McAndrew, C; Tomlin, K; Westwood, I; Burke, R; van Montfort, R; Workman, P (2019-06)
      Genomic alterations in cancer cells result in vulnerabilities that clinicians can exploit using molecularly targeted drugs, guided by knowledge of the tumour genotype. However, the selective activity of these drugs exerts ...
    • 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 ...
    • Evaluation of APOBEC3B Recognition Motifs by NMR Reveals Preferred Substrates. 

      Liu, M; Mallinger, A; Tortorici, M; Newbatt, Y; Richards, M; Mirza, A; van Montfort, RLM; Burke, R; Blagg, J; Kaserer, T (2018-09)
      APOBEC3B (A3B) deamination activity on ssDNA is considered a contributing factor to tumor heterogeneity and drug resistance in a number of human cancers. Despite its clinical impact, little is known about A3B ssDNA substrate ...
    • Exploiting evolutionary steering to induce collateral drug sensitivity in cancer. 

      Acar, A; Nichol, D; Fernandez-Mateos, J; Cresswell, GD; Barozzi, I; Hong, SP; Trahearn, N; Spiteri, I; Stubbs, M; Burke, R; Stewart, A; Caravagna, G; Werner, B; Vlachogiannis, G; Maley, CC; Magnani, L; Valeri, N; Banerji, U; Sottoriva, A (2020-04-21)
      Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another ...
    • Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70. 

      Cheeseman, MD; Westwood, IM; Barbeau, O; Rowlands, M; Dobson, S; Jones, AM; Jeganathan, F; Burke, R; Kadi, N; Workman, P; Collins, I; van Montfort, RLM; Jones, K (2016-05-11)
      HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought ...
    • A fragment-based approach applied to a highly flexible target: Insights and challenges towards the inhibition of HSP70 isoforms. 

      Jones, AM; Westwood, IM; Osborne, JD; Matthews, TP; Cheeseman, MD; Rowlands, MG; Jeganathan, F; Burke, R; Lee, D; Kadi, N; Liu, M; Richards, M; McAndrew, C; Yahya, N; Dobson, SE; Jones, K; Workman, P; Collins, I; van Montfort, RLM (2016-10-06)
      The heat shock protein 70s (HSP70s) are molecular chaperones implicated in many cancers and of significant interest as targets for novel cancer therapies. Several HSP70 inhibitors have been reported, but because the majority ...
    • Fragment-based screening identifies molecules targeting the substrate-binding ankyrin repeat domains of tankyrase. 

      Pollock, K; Liu, M; Zaleska, M; Meniconi, M; Pfuhl, M; Collins, I; Guettler, S (2019-12-13)
      The PARP enzyme and scaffolding protein tankyrase (TNKS, TNKS2) uses its ankyrin repeat clusters (ARCs) to bind a wide range of proteins and thereby controls diverse cellular functions. A number of these are implicated in ...
    • Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. 

      Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; Aleksandrov, R; Harrell, MI; Menon, M; Brough, R; Campbell, J; Frankum, J; Ranes, M; Pemberton, HN; Rafiq, R; Fenwick, K; Swain, A; Guettler, S; Lee, J-M; Swisher, EM; Stoynov, S; Yusa, K; Ashworth, A; Lord, CJ (2018-05-10)
      Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
    • Genomic and Transcriptomic Determinants of Therapy Resistance and Immune Landscape Evolution during Anti-EGFR Treatment in Colorectal Cancer. 

      Woolston, A; Khan, K; Spain, G; Barber, LJ; Griffiths, B; Gonzalez-Exposito, R; Hornsteiner, L; Punta, M; Patil, Y; Newey, A; Mansukhani, S; Davies, MN; Furness, A; Sclafani, F; Peckitt, C; Jiménez, M; Kouvelakis, K; Ranftl, R; Begum, R; Rana, I; Thomas, J; Bryant, A; Quezada, S; Wotherspoon, A; Khan, N; Fotiadis, N; Marafioti, T; Powles, T; Lise, S; Calvo, F; Guettler, S; von Loga, K; Rao, S; Watkins, D; Starling, N; Chau, I; Sadanandam, A; Cunningham, D; Gerlinger, M (2019-07)
      Despite biomarker stratification, the anti-EGFR antibody cetuximab is only effective against a subgroup of colorectal cancers (CRCs). This genomic and transcriptomic analysis of the cetuximab resistance landscape in 35 RAS ...
    • High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers. 

      Anderhub, SJ; Mak, GW-Y; Gurden, MD; Faisal, A; Drosopoulos, K; Walsh, K; Woodward, HL; Innocenti, P; Westwood, IM; Naud, S; Hayes, A; Theofani, E; Filosto, S; Saville, H; Burke, R; van Montfort, RLM; Raynaud, FI; Blagg, J; Hoelder, S; Eccles, SA; Linardopoulos, S (2019-10)
      BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly ...
    • High-resolution cryo-EM proteasome structures in drug development. 

      Morris, EP; da Fonseca, PCA (2017-06)
      With the recent advances in biological structural electron microscopy (EM), protein structures can now be obtained by cryo-EM and single-particle analysis at resolutions that used to be achievable only by crystallographic ...
    • Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA. 

      Kong, M; Cutts, EE; Pan, D; Beuron, F; Kaliyappan, T; Xue, C; Morris, EP; Musacchio, A; Vannini, A; Greene, EC (2020-07)
      Structural maintenance of chromosomes (SMC) complexes are essential for genome organization from bacteria to humans, but their mechanisms of action remain poorly understood. Here, we characterize human SMC complexes condensin ...
    • 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 ...