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UvrD acts in nucleotide excision repair by using its helicase/translocase activity to induce RNA polymerase backtracking, enabling repair enzymes to access DNA lesions.

Duan and Kaushik et al. reveal the structural basis of how Escherichia coli and Thermus thermophilus RNA polymerases initiate transcription from Np₄A alarmones producing Np₄-capped transcripts. The caps form various interactions with a polymerase during initial steps, influencing capping efficiency.

An ultra-high-resolution chromatin organization map of E. coli, using Micro-C, reveals intricate chromatin structures involved in the silencing of horizontally transferred genes and those associated with active operons.

Conditional cysteine restriction in mice causes substantial weight loss, exceeding that seen with essential amino acid restriction, by activating the integrated stress and oxidative stress responses, and by unexpectedly depleting coenzyme A, leading to metabolic inefficiency.

Here, using cryo-EM and biochemical methods, the authors demonstrate that second messenger (p)ppGpp regulates the bacterial RNA polymerase by binding to a site that is functionally relevant during transcriptional elongation but not initiation. Moreover, they demonstrate that binding to that site bears functional implications for nucleotide excision DNA repair and genome stability.

A collection of RNA polymerase mutants spanning all possible substitutions of the rifampicin binding site is generated and characterized, increasing our understanding of antibiotic mechanisms and bacterial physiology.

The exact mechanism by which cellular RNA polymerases translocate and maintain exceptionally high fidelity during transcription remains an important unresolved issue. Two recent structural studies of yeast RNA polymerase II in complex with its potent inhibitor, the fungal toxin α-amanitin, address this matter by describing crucial and surprising details about the dynamic organization of the enzyme catalytic center.

Direct time-resolved single-molecule observations of promoter search by Escherichia coli RNA polymerase indicate no evidence of facilitated diffusion, according to a new report.

Here, using proteomics, next-generation sequencing, biochemistry and cryo-EM, the authors delineate the role of CedA as an unconventional transcription factor in Escherichia coli, which protects from different stressors, including antibiotics, by regulating the transcriptional landscape.

Transcription-Coupled DNA repair has been classically defined as the preferential repair of the template strand (TS) over the non-template strand (NTS). Here the authors challenge this classic model of TCR by using a genome-wide repair assay, CPD-seq, as well as RNA-seq, to show that TCR occurs across the entire E. coli genome – including NTS and intergenic regions.

Computational, molecular and structural analyses reveal the presence of bacterial histones that bind DNA to form dense, DNA-enveloping fibres in Bdellovibrio bacteriovorus.

Integrated structure–function studies show that transcription-coupled DNA repair (TCR)—rather than global genomic repair—is responsible for most chromosomal repair events in bacteria, and that TCR mainly occurs independently of the Mfd translocase.

Maximum-depth sequencing (MDS), a new method of detecting extremely rare variants within a bacterial population, is used to show that mutation rates in Escherichia coli vary across the genome by at least an order of magnitude, and also to uncover mechanisms of antibiotic-induced mutagenesis.

A genome-wide Tn-seq analysis of the rpoB H526Y mutant, a rifampicin-resistant Escherichia coli strain, identifies non-essential genes that modulate the fitness cost of mutations in the bacterial RNA polymerase that confer antibiotic resistance.

Hydrogen sulfide (H2S) production in Escherichia coli is controlled by the sulfurtransferase 3MST. Here, the authors describe an alternative mechanism for H2S biosynthesis via activation of the thiosulfate sulfurtransferase PspE, a process mediated by the transcription factor YcjW.

Glycogen is a storage form of glucose in cells. Here, Gusarovet al. show that glycogen-derived glucose can be used to quickly regenerate the antioxidant glutathione and that inhibiting glycogen synthesis extends C. eleganslifespan, whereas glycogen accumulation drives organismal ageing in worms.

Reactive oxygen species are required for the long lifespan, and glutathione is an antioxidant. Here the authors show that limiting the consumption of dietary thiols, including those naturally derived from the microbiota, increases proteotoxic stress resistance in worms and human cells, and extends C. elegans lifespan.

A crystal structure of the antibiotic myxopyronin bound to bacterial RNA polymerase (RNAP) reveals insights into how the antibiotic binds to the transcription initiation complex and the mechanism of open complex formation.

Cryo-EM analysis of the human CST–Polα/primase complex reveals a metazoan-specific mode of interaction between CST and DNA polymerase α that is proposed to function in telomeric recruitment of Polα/primase for C-strand maintenance.

Rho is a general transcription termination factor in bacteria, but the mechanism by which it disrupts the RNA polymerase (RNAP) elongation complex is unknown. Here, Rho is shown to bind tightly to the RNAP throughout the transcription cycle, with the formation of the RNAP–Rho complex being crucial for termination. Furthermore, RNAP is proposed to have an active role in Rho termination through an allosteric mechanism.

Polycomb Repressive Complex 2 (PRC2) is a histone methyltransferase whose silencing activity is regulated in part by the selective incorporation of its catalytic subunits EZH1 or EZH2. Here, the authors capture an EZH1-containing PRC2 dimer on a nucleosome, demonstrating significant conformational changes during the process.

Structures of Cdc48 with heterodimeric cofactor Ufd1–Npl4 reveal the location of Npl4's MPN domain above Cdc48’s central pore, thus suggesting how Npl4 engages with polyubiquitinated substrates and promotes their translocation into the ATPase.

Small molecules and peptide inhibitors have their benefits and faults when it comes to inhibiting protein-protein interactions. Here, the authors designed a peptoid-peptide hybrid that inhibited β-catenin/TCF interactions, leading to inhibition of Wnt signalling in models of prostate cancer.

The cryo-EM structure of DNA-assembled histone pairs Hβ-Hα and Hδ-Hγ from Marseillevirus, a nucleocytoplasmic large DNA virus, reveals that these proteins form viral nucleosomes with highly conserved features when compared to canonical eukaryotic nucleosomes.

To ensure replication success, DNA polymerases must negotiate encounters with actively transcribing RNA polymerases that share the genome. This Review highlights the strategies used by prokaryotic and eukaryotic cells to minimize the consequences of collisions between replication forks and transcription complexes to effect faithful DNA replication without compromising gene expression.

Transcriptional pausing can be achieved by 6-nitropiperonyloxymethyl modification, which can halt RNAP without causing backtracking and be efficiently removed by short illumination with a moderately intense UV light.

Ruff et al. demonstrate that phosphorylation of the androgen receptor and 14-3-3 ζ by PIM1 kinase coordinates their interaction and chromatin occupancy at genes involved in cell migration and invasion. The authors conclude that PIM1 phosphorylation of these substrates regulates the AR transcriptome in prostate cancer cells.