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  • Journal article

  • Stem cell quiescence requires PRC2/PRC1-mediated mitochondrial checkpoint

    • Authors : Ishibashi, JR (2021)

  • Both normal and tumorous stem cells can arrest cell division, avoid apoptosis, and then regenerate lost daughter cells following acute genotoxic insult. This protective, reversible proliferative arrest, known as “quiescence,” is still poorly understood. Here, we show that mTOR-regulated mitophagy is required for radiation insult-induced quiescence in Drosophila germline stem cells (GSCs). In GSCs, depletion of mito-fission (Drp1) or mitophagy �...
  • Journal article

  • CheSPI: Chemical shift Secondary structure Population Inference

    • Authors : Nielsen, Jakob Toudahl (2021)

  • NMR chemical shifts (CSs) are delicate reporters of local protein structure, and recent advances in random coil CS (RCCS) prediction and interpretation now offer the compelling prospect of inferring small populations of structure from small deviations from RCCSs. Here, we present CheSPI, a simple and efficient method that provides unbiased and sensitive aggregate measures of local structure and disorder. It is demonstrated that CheSPI can p...
  • Journal article

  • Comparative host interactomes of the SARS-CoV-2 nonstructural protein 3 and human coronavirus homologs

    • Authors : Almasy, Katherine M. (2021)

  • Human coronaviruses have become an increasing threat to global health; three highly pathogenic strains have emerged since the early 2000s, including most recently SARS-CoV-2, the cause of COVID-19. A better understanding of the molecular mechanisms of coronavirus pathogenesis is needed, including how these highly virulent strains differ from those that cause milder, common-cold like disease. While significant progress has been made in understanding how SARS-CoV-2 ...
  • Journal article

  • Proteomic analysis identifies novel binding partners of BAP1

    • Authors : Baas, Roy (2021)

  • BRCA1-associated protein 1 (BAP1) is a tumor suppressor and its loss can result in mesothelioma, uveal and cutaneous melanoma, clear cell renal cell carcinoma and bladder cancer. BAP1 is a deubiquitinating enzyme of the UCH class that has been implicated in various cellular processes like cell growth, cell cycle progression, ferroptosis and ER metabolic stress response. ASXL proteins activate BAP1 by forming the polycomb repressive deubiqui...
  • Journal article

  • HaloTag9: an engineered protein tag to improve fluorophore performance

    • Authors : Frei, Michelle S. (2021)

  • HaloTag9 is an engineered variant of HaloTag7 with up to 40% higher brightness and increased fluorescence lifetime when labeled with fluorogenic rhodamines. Moreover, combining HaloTag9 with HaloTag7 and other fluorescent probes enabled live-cell multiplexing using a single fluorophore and the generation of a fluorescence lifetime-based biosensor. The increased brightness of HaloTag9 and its use in fluorescence lifetime multiplexing makes it a...
  • Journal article

  • Structure-based design of selective salt-inducible kinase (SIK) inhibitors

    • Authors : Tesch, Roberta (2021)

  • Salt-inducible kinases (SIKs) are key metabolic regulators. Imbalance of SIK function is associated with the development of diverse cancers, including breast, gastric and ovarian cancer. Chemical tools to clarify the roles of SIK in different diseases are, however, sparse and are generally characterized by poor kinome-wide selectivity. Here, we have adapted the pyrido[2,3-d]pyrimidin-7-one-based PAK inhibitor G-5555 for the targeting of SIK, by exploiting differences i...
  • Journal article

  • A molecular toolbox for ADP-ribosyl binding proteins

    • Authors : Tsowa, Swen (2021)

  • Proteins interacting with ADP-ribosyl groups are often involved in disease-related pathways or in viral infections, which makes them attractive targets for the development of inhibitors. Our goal was to develop a robust and accessible assay technology that is suitable for high-throughput screening and applicable to a wide range of proteins acting as either hydrolysing or non-hydrolysing binders of mono and poly-ADP-ribosyl groups. As a fou...
  • Journal article

  • Histone sequence variation in divergent eukaryotes facilitates diversity in chromatin packaging

    • Authors : Patwal, Indu (2021)

  • The histone proteins defining nucleosome structure are highly conserved in common model organisms and are frequently portrayed as uniform chromatin building blocks. We surveyed over 1700 complete eukaryotic genomes and confirm that almost all encode recognisable canonical core histones. Nevertheless, divergent eukaryotes show unrecognised diversity in histone sequences and offer an opportunity to observe the potential for nucleosome variation. Recombinant his...