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To perch safely, large birds minimize the distance flown after stalling when swooping up from a dive to a perch, but not the time or energy required.

Biochemical and structural analysis demonstrate that simultaneous detection of poly-lysine in the exit tunnel and poly(A) in the decoding center allows ribosomes to detect aberrant mRNAs, stall elongation and trigger downstream quality control pathways.

Scientists demonstrate an optical analogue of aerodynamic lift, in which an airfoil-shaped refractive object can be controlled through the radiation pressure induced by refracted and reflected rays of light.

Myosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Here, the authors show that a single phosphorylation event can modulate actin-activated ATPase activity and change the mechanical properties of myosin-VI.

Encounters between the replication and transcription machineries occur frequently in bacterial cells and are detrimental to fitness. Here, Grossman, Wang and colleagues review the two different types of replication–transcription conflict and describe the mechanisms that bacteria use to prevent and resolve these conflicts.

DNA analysis of ancient dental calculus samples revealed distinct oral microbial communities, including the archaeon Methanobrevibacter, which was associated with hygiene, diet and health.

During gene transcription, RNA polymerase (Pol) II moves forward along DNA and synthesizes mRNA. However, Pol II can also move backwards and stall, which is important for regulatory purposes or when the polymerase hits an obstacle such as a nucleosome. This arrested state is reactivated by the transcription factor TFIIS. Here, a crystal structure is presented of a backtracked yeast Pol II complex in which the backtracked RNA can be observed, plus a structure of a backtracked complex that contains TFIIS. A model is presented for Pol II backtracking, arrest and reactivation during transcription elongation.

Compound MMV006833 inhibits ring-stage development of Plasmodium falciparum. Here, the authors show that it targets lipid transfer enzyme PfSTART1 and prevents PfSTART1 from expanding the vacuole membrane encasing the parasite after red blood cell invasion, thereby blocking parasite growth.

As the rates of replication and transcription are different, the machineries that carry out these processes are bound to clash on DNA. In contrast to results from head-on collisions, co-directional encounters have been shown to have mild effects in vitro, requiring no additional replication restart factors. It is now shown that in bacterial cells, both types of events require the activities of restart proteins to resume replication when a transcription complex is encountered.

Grant Stewart, Andrew Jackson, Christopher Mathew, Fowzan Alkuraya and colleagues identify a novel replication fork protein, DONSON, which is important for maintaining genome stability. Mutations in DONSON cause microcephalic dwarfism and lead to stalled replication forks and DNA damage.

The authors review the role of glycosylation and its subtypes in DNA and RNA-sensing pathways within host innate immunity.

Here, Geoghegan, Evelyn et al. provide a lattice light-sheet microscopy based 4D imaging pipeline to quantitatively investigate Plasmodium spp. invasion and show that the nascent parasitophorous vacuole is predominantly formed from host’s erythrocyte membrane and undergoes continuous remodeling throughout invasion.

Mutations in the BAF SWI/SNF complex subunits are frequent in cancers but selective therapeutic approaches are not available yet. Here, the authors demonstrate that defects ofARID1Aand other subunits sensitizes cancer cells to the DNA checkpoint kinase inhibitor ATR in a synthetic lethal manner.

The ‘collateral’ homozygous deletion of essential redundant housekeeping genes in cancer genomes is shown to confer therapeutic vulnerability on cancer cells with the deletion, without affecting genomically intact normal non-cancerous cells, suggesting new therapeutic opportunities.

Physical non-equilibria can drive cycles of replication and selection chemistries that play a role in the prebiotic replication of DNA and RNA. This Perspective offers insights from astrophysics, geoscience and microfluidics on how various environments on early Earth could have hosted such reactions.

Synthetic lethality has emerged as a novel approach to treat cancer. Inhibitors of poly (ADP-ribose) polymerase, a target that has synthetic lethality withBRCAmutations, have already shown promise in clinical trials. The authors of this Review describe the clinical application of synthetic lethality for patients with breast cancer, and discuss biomarkers that can be used to select patients who will respond to this therapy. Other potential genes that could be involved in synthetic lethality, and are thus new targets, are also explored.

To correct the market failure around pediatric cell and gene therapies, the authors propose a new model to lead late-stage development and commercialize these therapies outside traditional routes.

Replication stress is a cause of genome instability in cancer cells. This Review discusses strategies to increase replicative stress by inhibiting the checkpoint kinases that coordinate DNA damage response and cell cycle, as well as combination strategies with other targeted therapies.

Inhibitors of poly(ADP-ribose)polymerase (PARP) have shown promise as therapeutic agents for the treatment of ovarian cancers with mutations inBRCA1 or BRCA2. By exploiting the synthetic lethal interaction that exists between PARP inhibition and BRCA mutations, these agents specifically kill cancer cells by targeting their DNA repair system. The authors of this Review describe the importance of BRCAmutations for the efficacy of PARP inhibitors. They also discuss the preclinical and clinical trial results of PARP inhibitors, the challenges related to the use of these agents, and future directions.

Alan Herbert discusses the properties of Z-DNA and Z-RNA, interactions with ADAR and other Z-binding proteins, and the role these elements play in disease. He also discusses the implication of Z-forming sites in genome evolution.

Recent studies have provided insights into the mechanisms that regulate DNA repair in specific cell-cycle phases and the pathways that ensure cell-cycle progression or arrest in normal and cancerous cells. Understanding how DNA repair is modulated during the cell cycle has important applications.

Inglese et al. develop a predictive model that computes multi-regional statistical morpho-functional mesoscopic traits from T1-weighted magnetic resonance imaging scans. Their model reliably discriminates people with Alzheimer’s disease-related pathologies from those without.