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Activation of telomerase or alternative lengthening of telomeres (ALT) is necessary for tumours to escape from dysfunctional telomere-mediated senescence. Anti-telomerase drugs might be effective in suppressing tumour growth in approximately 85–90% of telomerase-positive cancer cells. However, there are still chances for these cells to bypass drug treatment after switching to the ALT mechanism to maintain their telomere integrity. But the mechanism underlying this switch is unknown. In this study, we used telomerase-positive cancer cells (HTC75) to discover the mechanism of the telomerase-ALT switch by inducing telomere-specific DNA damage, alpha-thalassemia X-linked syndrome protein (ATRX) knockdown and deletion of death associated protein (DAXX). Surprisingly, two important ALT hallmarks in the ALT-like HTC75 cells were observed after treatments: ALT-associated promyelocytic leukaemia bodies (APBs) and extrachromosomal circular DNA of telomeric repeats. Moreover, knocking out hTERT by utilizing the CRISPR/Cas9 technique led to telomere elongation in a telomerase-independent manner in ALT-like HTC75 cells. In summary, this is the first report to show that inducing telomeric DNA damage, disrupting the ATRX/DAXX complex and inhibiting telomerase activity in telomerase-positive cancer cells lead to the ALT switch.

All‐inorganic halide perovskite nanocrystals (PNCs) have drawn increasing attention owing to their splendid optical properties. However, such nanomaterials suffer from intrinsic instability, greatly limiting their practical application. Meanwhile, environmental regulation has restricted the emissions of volatile organic compounds (VOCs), initiating a search for alternative approaches to PNC synthesis and film forming. Herein, fiber‐spinning chemistry (FSC) is proposed for easy‐to‐perform synthesis of highly stable PNC fibrous films. The FSC process utilizes spinning fibers as reactors, reducing the generation of VOCs. This method enables the fabrication of CsPbX3 (X = Cl, Br, I) PNCs/poly(methyl methacrylate)/thermoplastic polyurethanes fibrous films at room temperature in one step, exhibiting tunable emission between 450 and 660 nm. Significantly, the in situ generation of PNCs in hydrophobic core–shell nanofibers results in highly improved fluorescence stability. PNCs/polymer fibrous films keep constant in photoluminescence (PL) after storage at atmosphere for 90 d and retain 82% PL after water immersion for 120 h (vs fluorescence quenching in 10 d in air or 5 h in water for pristine PNCs). The PNCs/polymer fibrous films endowed with superior optical stability and great flexibility show promising potentials in flexible optoelectronic applications. This work paves a facile way toward high‐performance nanoparticles/polymer fibrous films.

Telomeres and telomere-binding proteins form complex secondary nucleoprotein structures that are critical for genome integrity but can present serious challenges during telomere DNA replication. It remains unclear how telomere replication stress is resolved during S phase. Here, we show that the BUB3-BUB1 complex, a component in spindle assembly checkpoint, binds to telomeres during S phase and promotes telomere DNA replication. Loss of the BUB3-BUB1 complex results in telomere replication defects, including fragile and shortened telomeres. We also demonstrate that the telomere-binding ability of BUB3 and kinase activity of BUB1 are indispensable to BUB3-BUB1 function at telomeres. TRF2 targets BUB1-BUB3 to telomeres, and BUB1 can directly phosphorylate TRF1 and promote TRF1 recruitment of BLM helicase to overcome replication stress. Our findings have uncovered previously unknown roles for the BUB3-BUB1 complex in S phase and shed light on how proteins from diverse pathways function coordinately to ensure proper telomere replication and maintenance.