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After mitosis, the nucleus must be rebuilt and chromatin decondensed to permit interphase genomic functions, but decondensation mechanisms are poorly understood. Now, the traditional cytoskeletal protein actin is shown to form transient nuclear filaments that are required for chromatin decondensation and nuclear expansion at mitotic exit.
Advances in stem cell research offer unprecedented insights into human biology and opportunities for clinical translation. They also raise many questions with social and ethical implications.
Small RNAs generated at DNA break sites are implicated in mammalian DNA repair. Now, a study shows that following the formation of DNA double-strand breaks, bidirectional transcription events adjacent to the break generate small RNAs that trigger the DNA damage response by local RNA:RNA interactions.
Membrane trafficking specificity between distinct compartments ensures that cargo proteins and lipids are delivered to their target organelle. However, accurate recognition of cargo carriers by tethering factors on target membranes is poorly understood. TBC1D23 is now identified as an adaptor that links endosome-derived vesicles with golgins at the trans-Golgi.
Michelini et al. show that RNA polymerase II is recruited to double-strand breaks to induce long non-coding RNAs and the generation of small DNA damage response RNAs that promote recruitment of DNA repair factors and repair.
Baarlink et al. identify a transient pool of nuclear F-actin, the dynamics of which are controlled by cofilin-1 that accumulates after mitosis and is important for chromatin reorganization in G1.
Organoids are a powerful tool to study both physiological and disease processes. A completely synthetic matrix assembled from exchangeable modular parts has been developed and not only supports proliferation of human intestinal organoids derived from pluripotent embryonic stem cells, but also augments subsequent ad vivo implantation into injured murine colon.
A variety of non-coding RNAs have been reported as endogenous sponges for cancer-modulating miRNAs. However, miRNA trapping by transcripts with protein-coding functions is less understood. The mRNA of TYRP1 is now found to sequester the tumour suppressor miR-16 on non-canonical miRNA response elements in melanoma, thereby promoting malignant growth.
PARP inhibitors (PARPi) kill BRCA1/2-mutated cancers, which become resistant when DNA repair functions are restored. Now, MUS81 nuclease inhibition due to EZH2 downregulation is found to restore DNA replication fork protection but not repair, leading to PARPi-resistance in mutant BRCA2 cells and patients. This challenges the DNA repair dominance in synthetic lethality.
Shin et al. identify TBC1D23 as an adaptor that interacts both with golgins and endosomal WASH and is required for the delivery of endosome-derived vesicles to the trans-Golgi.
O’Farrell et al. show that class III PI3K regulates epithelial integrity through endosomal LKB1. Class III PI3K inactivation dysregulates LKB1 to alter cell polarity, and the PtdIns3P effector WDFY2 regulates LKB1.
Cdk1-mediated phosphorylation of threonine and serine residues on cell cycle regulators needs to be removed after mitosis. Hein et al. show that the known preference of the PP2A–B55 phosphatase for threonine provides temporal regulation of mitotic exit.
Liu et al. find that PKM2 methylated by CARM1 inhibits Ca2+ influx from endoplasmic reticulum to mitochondria, thus restraining mitochondrial oxidative phosphorylation while promoting aerobic glycolysis and breast cancer growth.
In the developing mouse pancreas, EGFR regulates apical polarity via PI(3)K and Rac1 and elicits different ligand-dependent effects: BTC enables β-cell commitment and EGF inhibits polarization of epithelial progenitors during the primary transition.
Cruz-Acuña et al. develop synthetic hydrogels that support the generation and expansion of viable human intestinal organoids from pluripotent stem cells and can be used as injectable vehicles for organoid engraftment and wound healing.
Boyd et al. monitored the effects of patient-derived acute myeloid leukaemia (AML) cells on human HSPCs in vivo and found that AML impairs bone marrow adipocyte differentiation, and this in turn impedes healthy endogenous haematopoiesis.
Rondinelli et al. show that EZH2-mediated H3K27me3 at stalled replication forks recruits MUS81 nuclease to facilitate fork degradation. Loss of EZH2 contributes to PARPi resistance in BRCA2-deficient tumours.
