Volume 24 Issue 1, January 2022

Understanding how cancers react to poly(ADP-ribose) polymerase (PARP) trapping on DNA is crucial to thwart PARP inhibitor resistance. A recent study finds that trapped PARP1 is removed via the ubiquitin-dependent segregase p97, and that perturbing this molecular cascade increases PARP inhibitor cytotoxicity.

Lipid metabolism is crucial for the execution of ferroptosis. A new study demonstrates that the function of the lipid metabolic enzyme ACSL4 is positively regulated by phosphorylation, leading to amplification of ferroptotic cell death. These results shed new light on the regulation of ferroptosis execution in cancer cells.

Nuclear pore complexes (NPCs) facilitate the fast, yet highly selective, nucleocytoplasmic transport of molecules. A recent study describes a multicolour imaging approach to chart the paths for cargo molecules through the human NPC with real-time 3D visualization of nucleocytoplasmic transport events with high spatial and temporal precision.

Cell fate determination by H3.3 deposition in haematopoietic stem and progenitor cells is largely unexplored. Two studies jointly support the idea that H3.3 maintains haematopoiesis balance and prevents endogenous retroviral element (ERV) activation through chromatin marks and transcriptome alterations.

Kathiriya et al. report that fibrotic signalling in the lung mesenchyme leads to transdifferentiation of human alveolar type 2 cells into KRT5⁺ basal cells, providing a mechanistic explanation for the pathology associated with severe lung injuries.

Samelson et al. report that BRD2 inhibition suppresses SARS-CoV-2 infection in epithelial cells and Syrian hamsters via reducing the transcription of host cell surface receptor ACE2.

Das et al. show that the copper transporter CTR1 functions as a redox sensor in endothelial cells. CTR1 is modified after redox stress, which induces CTR1–VEGFR2 complex formation and promotes VEGFR2 signalling and angiogenesis.

Mirman et al. report that the primary function of the shieldin complex in double-strand break repair in BRCA1-deficient cells is the recruitment of the CST–Polα–primase complex to conduct fill-in synthesis.

Krastev et al. report that trapped PARP1 undergoes SUMOylation, followed by ubiquitylation, resulting in the recruitment of the p97 ATPase to remove trapped PARP1 from chromatin and prevent PARP inhibitor-induced cytotoxicity.

Han et al. report that the Hippo pathway kinases LATS1 and LATS2 phosphorylate the heavy metal response transcription factor MTF1, leading to attenuation of heavy metal response gene transcription and cellular detoxification.

Through CRISPR–Cas9 and kinase inhibitor screening, Zhang et al. show that PKCβII phosphorylates and activates ACSL4 to enhance polyunsaturated fatty acid-containing lipid biosynthesis, thereby promoting accumulation of lipid peroxidation and ferroptosis.

Guo et al. show that H3.3 prevents the premature exhaustion of HSCs and differentiation into granulocyte-macrophage progenitors by safeguarding the interplay between H3K27me3 and H3K9me3 marks.

Chowdhury, Sau and Musser report a multicolour imaging approach that enables the 3D visualization of cargo transport trajectories relative to a super-resolved nuclear pore complex scaffold in non-fixed permeabilized cells.