Search

Bacterial homologous recombination involves the actions of RadA and RecA to promote single-stranded DNA integration. Here the authors report the structure of RadA fromStreptococcus pneumoniaeand demonstrate that it acts as a hexameric DnaB-type helicase.

Tuberculosis is a major global health threat. Here, the authors develop a single-cell drug discovery approach and identify a compound that tunes bacterial phenotypic variation. This enhances the activity of anti-tubercular drugs against the pathogen.

CRISPR-Cas immunity systems safeguard prokaryotic genomes by inhibiting the invasion of mobile genetic elements. Here, the authors show that insertion sequences can efficiently insert into cas genes, thus inactivating CRISPR defenses and increasing bacterial susceptibility to foreign DNA invasion.

Genome engineering in bacteria remains a complex multistep process. Here, the authors developed make-or-break Prime Editing, a precise method for genetic modification in Streptococcus pneumoniae that enables high-throughput and scalable genome editing.

Prophage induction is a fundamental process in the phage life cycle. Here the authors show that the final stage of prophage induction in Staphylococcus aureus is controlled by the ClpX protease, unveiling and unexpected role for ClpX in phage biology.

Many bacteria release DNA and membrane vesicles through unclear mechanisms. Here, the authors show that a prophage endolysin is involved in the explosive lysis of a sub-population of cells in Pseudomonas aeruginosa, releasing cytoplasmic content and membrane fragments that rapidly form membrane vesicles.

Genetic evidence has implicated the SOS-induced translesion DNA polymerase DinB (Pol IV) in error-prone recombination. Now biochemical analyses show that Pol IV outcompetes high-fidelity polymerases during the extension of D-loop recombination intermediates under SOS response conditions, providing new insight into the mechanism of stress-induced mutations in Escherichia coli.

The HOP2-MND1 heterodimer is essential for homologous recombination. Here, Bugreev et al. analyse its mechanism of action in vitroand show that HOP2-MND1 stabilizes an active conformation of Rad51, thus triggering DNA strand exchange.

Random DNA mutagenesis provides genetic diversity both in nature and the laboratory. Here, Badran and Liu present a potent, inducible, broad-spectrum and vector-based mutagenesis system in E. coli that surpasses the mutational efficiency and spectra of the most widely used in vivo and in vitromutagenesis methods.

Horizontal gene transfer is important for bacterial evolution but the molecular basis of its fitness costs remain unclear. Here the authors show that fitness costs produced by a plasmid in P. aeruginosaare alleviated by mutations in recently acquired genes encoded in mobile genetic elements.

Biocontainment is a key to developing safe genetically-engineered microbes (GEMs). Here the authors demonstrate genetically stable CRISPR-based kill switches that control GEMs’ viability in animal hosts, enabling their safe biomedical applications.

Experimental evolution in engineered Escherichia coli shows that amplification-mediated gene expression tuning, resulting from intrinsic instability of copy-number mutations, is a mechanism of gene expression regulation in fluctuating environments.

VVD-133214, a clinical-stage, covalent allosteric inhibitor of the helicase WRN, was well tolerated in mice and led to robust tumour regression in multiple microsatellite-instability-high colorectal cancer cell lines and patient-derived xenograft models.

Dimethylsulphide (DMS) is a volatile compound produced by marine microbes through degradation of dimethylsulphoniopropionate (DMSP). Here, Carrión et al.describe an alternative pathway for DMS production from methanethiol that is widespread among bacteria, especially from soil environments.

Structure-specific endonucleases play an important role in several DNA repair pathways. Here the authors present structures of the endonuclease XPF-ERCC1 in complex with SLX4, SLX4IP, and DNA. Combined with functional analysis, these results provide insight into the mechanisms of XPF-ERCC1 recruitment and activation during DNA repair.

Structural and mechanistic data of the ADP-ribosyltransferase DarT demonstrate the role of ADP-ribosylation of DNA by this enzyme in generating toxicity and regulating cellular signalling processes in bacteria.

Nucleosome-remodelling complexes can slide or eject histones, or incorporate histone variants, but they share an ATPase–translocase 'motor' and a common DNA translocation mechanism. In a unifying 'hourglass' model of remodeller function, the different remodeller subfamilies use different modules for targeting to nucleosomes but converge on a DNA translocation mechanism and then diverge again to achieve various outcomes.

The oncogenic chromatin remodeler ALC1 (amplification in liver cancer 1), also known as CHD1L is an ATP-dependent chromatin remodeler that relaxes chromatin and plays an important role in the poly(ADP-ribose) polymerase 1 -mediated DNA repair pathway. Here, the authors present the ALC1 crystal structure and a cryo-EM structure of ALC1 bound to a nucleosome, which reveal that ALC1 is autoinhibited and how it becomes activated.

Otoupal et al. use a systematic approach to investigate the effects of fitness neutral gene perturbations and antibiotic synergy in Escherichia coli. These neutral fitness interactions worked as co-therapies in a Salmonella enterica infection and informed the design of re-sensitization therapies in multi-drug resistant E. coli and Klebisiella pneumoniae clinical isolates.

Dmc1 is a Rad51 paralog with a central role in meiotic recombination. Both Rad51 and Dmc1 form filaments on single-stranded DNA that can promote strand exchange with similar efficiencies. Now, D loops formed with DMC1 are shown to be more resistant to dissociation by BLM or RAD54 than those formed with RAD51.

Prophages are quiescent bacterial viruses that, when activated, produce viral particles and kill their host cells. Here, Haaber et al. show that these viral particles can mediate the transfer of antibiotic resistance genes from neighbouring cells back to the remaining prophage-containing cells.

Deletion of cellular NAD+ via Sir2-depentent NADase provides immunity against phage infection in the Sir2-HerA immune system. Here the authors reveal supramolecular assembly for the allosteric activation on Sir2 NADase function in the Sir2-HerA antiphage system.

Here the authors fuse hRad51 and variants thereof to Cas9 nickase to facilitate homology-directed repair without generating double strand breaks, minimizing indel formation and off-target editing. This tool represents progress towards the goal of performing HDR without an excess of undesired side products.

The ATP-dependent chromatin assembly factor (ACF) generates and maintains nucleosome spacing by constantly moving a nucleosome towards the longer flanking DNA faster than the shorter flanking DNA. But how the enzyme moves back and forth between both sides of a nucleosome to accomplish bidirectional movement is unknown. Nucleosome movement is now shown to depend cooperatively on two ACF molecules, indicating that ACF functions as a dimer of ATPases.