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  • During the repair of DNA breaks by homologous recombination, damaged DNA seeks out intact, similar in sequence segments to use as a template. In this issue, Piazza, Bordelet and colleagues describe three-dimensional chromosome architecture remodelling during homologous recombination and show that cohesin restricts homology search in cis, independently of sister chromatid cohesion.

    • Argyris Papantonis
    • Vassilis Roukos
    News & Views
  • FGFR-altered triple negative breast cancer (TNBC) develops adaptive resistance to FGFR inhibitor therapy. A new study shows that sustained FGFR inhibition causes SWI/SNF complex eviction at YAP-recruited enhancers followed by increased mTORC1 activity. Dual inhibition of YAP or mTORC1 and FGFR has a synergistic effect on tumour growth.

    • Krystal A. Orlando
    • Paul A. Wade
    News & Views
  • The WAVE regulatory complex is well known as an orchestrator of actin dynamics at the leading edge of migrating cells. A recent study shows how mechanical effects can regulate the WAVE complex and explains the importance of forces generated by actin filaments to control new actin generation at the leading edge.

    • Laura M. Machesky
    • Robert H. Insall
    News & Views
  • The underlying molecular and cellular mechanisms for asthma remain incompletely understood. A new study now shows that eosinophils release DNA traps that stimulate pulmonary neuroendocrine cell-mediated amplification of the allergic asthma response.

    • Barsha Dash
    • Xin Sun
    News & Views
  • Clathrin- and dynamin-independent endocytosis is considered a major ‘default’ uptake route for cells, but a recent study describes the selective recruitment of integrin-adhesion receptor cargoes via the endocytic adaptor Swip1, which promotes breast cancer invasion and metastasis.

    • Patrick T. Caswell
    News & Views
  • Cells respond to stimuli by reorganizing their contents into subcellular structures. New research demonstrates that yeast pyruvate kinase Cdc19 interacts with fructose-1,6-bisphosphate to coordinate disassembly of stress granules. These findings reveal how proteins can directly sense the cellular energy state to facilitate adaptive reorganization.

    • Christopher M. Jakobson
    • Daniel F. Jarosz
    News & Views
  • The collapse of DNA replication forks leads to the formation of single-ended DNA double-strand breaks. One would have assumed that these breaks would be repaired as soon as possible. However, a recent study suggests that a delay in DNA polymerase θ-mediated end joining until mitosis, orchestrated by BRCA2 and RAD52, favors genomic stability.

    • Michalis Petropoulos
    • Thanos D. Halazonetis
    News & Views
  • Enhancer of zeste homolog 2 (EZH2) has been shown to promote development of castration-resistant prostate cancer (CRPC) through various mechanisms. A new study now shows that a phosphorylated EZH2 interacts with the androgen receptor (AR) and reprograms AR transcriptional activity to facilitate transition of CRPC into a lineage infidelity state.

    • Li Xin
    News & Views
  • Mice deficient in the piRNA pathway display sterility only in males. Taking advantage of a more representative piRNA pathway in golden hamsters, three studies now demonstrate that the piRNA pathway is essential for fertility in hamsters of both sexes and thus strongly link this small RNA pathway to fertility regulation in both men and women.

    • Yongjuan Guan
    • P. Jeremy Wang
    News & Views
  • Stem cells are the functional units of tissue repair but do not act alone. Studies on flatworms now reveal specialized populations of differentiated cells that transiently emerge to coordinate whole-body regeneration. The stem-cell-centric view of repair processes must be revised to account for the importance of cell fate dynamics beyond the niche.

    • Stephanie J. Ellis
    • Elaine Fuchs
    News & Views
  • Tissue-resident stem cells are capable of remarkable plasticity in areas of tissue damage, where inflammatory cells accumulate as part of the reparative response. A study in the lung now provides critical insight on how inflammatory signals alter cell-to-cell Notch signalling within the airway niche to drive stem cell plasticity.

    • Jaymin J. Kathiriya
    • Tien Peng
    News & Views
  • With advanced high-throughput technologies, scientists can now use transcriptional signatures to study melanocytes as they become cancer. A new study identifies transcriptional programs at single-cell resolution across platforms and species, which enables prediction of melanoma prognosis and response to immune-checkpoint inhibitor therapy.

    • Alicia M. McConnell
    • Leonard I. Zon
    News & Views
  • Lineage-specific gene expression programs in multicellular organisms are controlled by balanced ON and OFF signals, amongst which heterochromatin regulates expression by restricting activation cues. A study now provides insights into mammalian heterochromatin organisation, function and interplay with lineage-specific transcription factors.

    • Adam Burton
    • Maria-Elena Torres-Padilla
    News & Views
  • Cells rely on two main pathways to repair DNA lesions, homologous recombination and non-homologous end-joining, and how they decide to use one machinery over the other is not clear. A recent study identifies ASTE1 as a regulator controlling pathway choice.

    • Yizhou Joseph He
    • Dipanjan Chowdhury
    News & Views
  • LKB1 is frequently mutated in lung, cervical and other types of cancers. To determine how LKB1 inactivation contributes to lung cancer progression, Pierce et al. employed a chromatin accessibility assay to reveal Sox17 as a key transcription factor downstream of LKB1, promoting lung cancer metastasis.

    • Skirmantas Kriaucionis
    News & Views
  • Neuronal mitochondria perturbation elicits a mitochondrial unfolded protein response (UPRmt) in peripheral tissues cell non-autonomously, dependent on the Wnt signalling pathway. A study now reveals that a Wnt-mediated increase in maternally inherited mitochondria DNA is responsible for transgenerational UPRmt induced by neuronal mitochondria perturbation.

    • Mooncheol Park
    • Meng C. Wang
    News & Views
  • Many endocytic uptake events depend on the ‘pinchase’ activity of dynamin. By measuring the orientation of single gold nanorods, a new study reveals that invaginated clathrin-coated endocytic pits undergo a strong rotational twist prior to or concomitant with their detachment.

    • Ludger Johannes
    • Cesar Augusto Valades-Cruz
    News & Views
  • A new study shows that the SARS-CoV-2 nucleocapsid protein represses the antiviral type I interferon response through direct interaction with the signalling adaptor protein MAVS. Targeting this process might be a useful therapeutic strategy to boost immunity against COVID-19.

    • Alessia Zotta
    • Alexander Hooftman
    • Luke A. J. O’Neill
    News & Views
  • A form of programmed cell death, necroptosis, in intestinal epithelial cells initiates mucosal inflammation. A study now finds that prostanoid EP4 receptor signalling interferes with RIPK1–RIPK3-dependent MLKL activation, thereby inhibiting necroptosis and accelerating resolution of inflammation.

    • Nicole C. Kaneider
    • Arthur Kaser
    News & Views
  • Intestinal organoids have been used to model development of the crypt–villus axis and uncover signalling pathways that govern the stem-cell niche and induce differentiation. Two studies now take advantage of intestinal organoids to measure the mechanical forces that drive morphogenesis of the crypt and fate specification of its resident cells.

    • Celeste M. Nelson
    News & Views