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Members of the polo-like kinase (PLK) family are crucial regulators of cell cycle progression, centriole duplication, mitosis, cytokinesis and the DNA damage response. Recent structural and molecular studies have revealed how such processes depend on the tight regulation of PLK abundance, activity, localization and interactions with other proteins, and how dysregulation may be associated with disease.

Polo-like kinase 1 is a key regulator of mitosis and is a candidate for drug development to treat cancer. Here, reduced expression of polo-like kinase 1 in adult mice has a minor impact on animal physiology, suggesting that polo-like kinase 1 inhibitors may be useful in the killing of tumour cells while sparing normal cells.

CRISPR-based gene drives have the potential to spread within populations and are considered as promising vector control tools. Here the authors show an anti-drive mosquito strain that prevents the spread and collapse of a population suppression gene drive in laboratory Anopheles mosquito large cage trials in complex ecological and behavioral conditions.

The Cdc2 (also called Cdk1) kinase is first activated at the centrosome to initiate mitosis in human cells. Hagan and colleagues demonstrate that in fission yeast, Cdc2 and Polo kinase activation at the spindle pole body remotely controls not only mitotic commitment but also ‘new end take off’, the initiation of bipolar growth in G2.

The molecular mechanisms underlying drug resistance in relapsed or refractory (rr) acute myeloid leukemia (AML) remain to be explored. Here, the use of bulk and single cell multi-omics and ex vivo drug profiling for 21 rrAML patients reveals mechanisms of resistance to the Bcl-2 inhibitor venetoclax and treatment vulnerabilities.

Andrew Jackson, Peter Nürnberg and colleagues identify mutations in PLK4 and TUBGCP6 in individuals with microcephaly, primordial dwarfism, retinopathy and other congenital anomalies. These findings extend the spectrum of human phenotypes associated with centriole dysfunction.

The balance between proliferation and differentiation is essential not only for the generation and maintenance of tissues, but also to prevent uncontrolled cell division and tumorigenesis. The mitotic kinase Aurora A coordinates cell-cycle events and asymmetric division by regulating localization of the cell fate determinant Numb through remodelling of the conserved PAR polarity complex.

Phosphatase enzymes are challenging to study due to a lack of specific inhibitors. Here, authors develop a chemical-genetic system to inhibit and characterize a major Ser/Thr phosphatase complex, and suggest this strategy, termed directSLiMs, could be used to inhibit other “undruggable” enzymes.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Experimental analysis of gene drive population dynamics has mostly been limited to small cage trials. Here the authors, to fill the gap between lab based studies and field studies, use large indoor cages and see population suppression without the emergence of resistant alleles

Lim et al. reconstitute in vitro the transition between metaphase and anaphase-like spindle midzone architectures and dissect the role of PRC1 phosphorylation by PLK and CDK1 in reorganizing the central spindle during mitosis.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Increasing reliance on antigen tests for SARS-CoV-2 screening may risk selection for variants not detected by these tests. Here, the authors identify a variant of this type circulating in Italy, estimate the potential impact of failure to detect the variant, and model testing strategies to mitigate the risk.

The CENP-A chaperone HJURP associates with Mis18α, Mis18β, and M18BP1 to target centromeres and deposit new CENP-A. Here the authors provide evidence that two repeats in human HJURP previously proposed to be functionally distinct are interchangeable and bind concomitantly to the 4:2:2 Mis18α:Mis18β:M18BP1 complex without dissociating it.

To minimize recombination losses and therefore increase the conversion efficiency of crystalline silicon solar cells, researchers have relied on passivating contacts. Here, the authors demonstrate a hole-selective passivating contact that exploits the firing step currently employed in industrial manufacturing.

SKAP and Astrin form a heterodimer that localizes to spindle microtubules and to mature microtubule-kinetochore attachments during mitosis. Here, the authors identify molecular requirements for the inter-subunit interaction of SKAP and Astrin and kinetochore recruitment.

Cyclin B1 and cyclin B2 regulate chromosome segregation through two distinct mechanisms.

Non-invasive monitoring of solid tumour growth in mice is difficult. In this study, the authors develop a system for monitoring the secretion of luciferase either from Gaussia princeps or Cypridina noctiluca in the blood of mice harbouring luciferase-labelled tumour cells, thus providing a system to monitor two different cell populations in vivo.

A survey of potency and efficacy of 2,025 clinically relevant two-drug combinations against 125 molecularly characterized breast, colorectal and pancreatic cancer cell lines identifies rare synergistic effects of anticancer drugs, informing rational combination treatments for specific cancer subtypes.

In a screen of 324 human cancer cell lines and utilising a systematic target prioritization framework, the Werner syndrome ATP-dependent helicase is shown to be a synthetic lethal target in tumours from multiple cancer types with microsatellite instability, providing a new target for cancer drug development.

Chromosomal instability leads to aneuploidy, a state of karyotype imbalance. By inducing controlled chromosome mis-segregation, Santaguida and colleagues show that aneuploidy can also instigate chromosomal instability.

Precision oncology relies on model systems that reflect the genomic heterogeneity of human cancers. Here the authors characterize a panel of 151 colorectal cancer cell lines with respect to genetic mutations, expression profiles and drug sensitivity to identify new therapeutic targets.

The life of RNAs is governed by a series of transcriptional and post-transcriptional steps. Here, authors developed Nanodynamo, an experimental and computational workflow for studying how the coordinated action of these steps shapes breast cancer gene expression programs at the subcellular level.

Clathrin light chains (CLCa and CLCb) are major constituents of clathrin-coated vesicles. Here authors find and structurally characterize the selective interaction between CLCa and the actin motor protein myosin VI which act together to generate the force that leads to invagination and fission at the apical surface.

Cells respond to increasing concentrations of EGF by altering the balance between EGFR phosphorylation and ubiquitination. Here the authors show that the establishment of an EGFR signaling threshold requires both a multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR.

The spindle-assembly checkpoint is a safety device that monitors the attachment of spindle microtubules to kinetochores and ensures the fidelity of chromosome segregation in mitosis. Molecular studies are finally starting to reveal the mechanisms of checkpoint activation and inactivation.

Observations from the JWST of the second brightest GRB ever detected, GRB 230307A, indicate that it belongs to the class of long-duration GRBs resulting from compact object mergers, with the decay of lanthanides powering the longlasting optical and infrared emission.

The burden of mosaic chromosomal alterations in blood-derived DNA, a type of clonal hematopoiesis, is associated with an increased risk for diverse types of infections, including sepsis and pneumonia.

A sex-distorter gene drive causes population collapse in the malaria mosquito.

Hundreds of computational resources have been developed that can be applied to repurposing existing drugs for new indications, making it challenging to select the right resource for a specific project. To help address this challenge, this article provides an overview of computational approaches to drug repurposing based on a comprehensive survey of available resources classified into hierarchical categories for a web catalogue, and presents an expert evaluation of selected resources, as well as case studies to illustrate their application.

A possible kilonova associated with a nearby, long-duration gamma-ray burst suggests that gamma-ray bursts with long and complex light curves can be spawned from the merger of two compact objects, contrary to the established gamma-ray burst paradigm.

A combination of real-world evidence and a reanalysis of phase 3 clinical trial data unveils KRAS codon G12 mutations as a biomarker of resistance to trifluridine/tipiracil in metastatic colorectal cancer.

PIP4Ks are phosphoinositide kinases often dysregulated in cancer. Here Poli and colleagues find that PIP4K2B is downregulated on soft substrates, and its depletion leads to altered nuclear mechanical properties and defects in cell spreading and motility.

Primary biliary cirrhosis is an autoimmune liver disease with poor therapeutic options. Here Cordell et al. a perform meta-analysis of European genome-wide association studies identifying six novel risk loci and a number of potential therapeutic pathways.

Gioia, Tavella et al. show that severe acute respiratory syndrome coronavirus 2 causes DNA damage through CHK1 degradation and impairs 53BP1 recruitment to DNA lesions. The induced DNA damage is associated with expression of pro-inflammatory cytokines and senescence markers.

With no cell lines available, investigating the aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs) has proved problematic. Here, Oikawa et al. establish a model of hFL-HCCs as a transplantable tumour line maintained in immune-compromised mice, which proves rich in cancer stem cells.