07/2020 - Filament formation by the translation factor eIF2B regulates protein synthesis in starved cells
Cells exposed to starvation have to adjust their metabolism to conserve energy and protect themselves. Protein synthesis is one of the major energy-consuming processes and as such has to be tightly controlled. Many mechanistic details about how starved cells regulate the process of protein synthesis are still unknown. Here, we report that the essential translation […]
07/2020 - Drug mechanism‐of‐action discovery through the integration of pharmacological and CRISPR screens
Low success rates during drug development are due, in part, to the difficulty of defining drug mechanism‐of‐action and molecular markers of therapeutic activity. Here, we integrated 199,219 drug sensitivity measurements for 397 unique anti‐cancer drugs with genome‐wide CRISPR loss‐of‐function screens in 484 cell lines to systematically investigate cellular drug mechanism‐of‐action. We observed an enrichment for […]
07/2020 - A micronutrient with major effects on cancer cell viability
Selenium is a micronutrient essential for the generation of selenoproteins, which function predominantly by detoxifying cellular reactive oxygen species. In this issue, Carlisle et al. describe a novel mechanism whereby perturbing selenium utilization via inhibition of SEPHS2, a component of the selenocysteine-biosynthesis pathway, results in selenide poisoning and cancer cell death.
07/2020 - A Human Pluripotent Stem Cell-based Platform to Study SARS-CoV-2 Tropism and Model Virus Infection in Human Cells and Organoids
SARS-CoV-2 has caused the COVID-19 pandemic. There is an urgent need for physiological models to study SARS-CoV-2 infection using human disease-relevant cells. COVID-19 pathophysiology includes respiratory failure but involves other organ systems including gut, liver, heart, and pancreas. We present an experimental platform comprised of cell and organoid derivatives from human pluripotent stem cells (hPSCs). […]
07/2020 - Human Condensin I and II Drive Extensive ATP-Dependent Compaction of Nucleosome-Bound DNA
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 I and II and unveil the architecture of the human condensin II complex, revealing two putative DNA-entrapment sites. Using single-molecule imaging, we demonstrate that both […]