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The challenge of transforming organized DNA structures into their metallized counterparts persists in the scientific field. Herein, the authors report the solution structure of a silver-metallized DNA duplex containing 7-deazapurines, demonstrating a methodology to create Ag-DNA systems with silver-modified Watson-Crick base pairs that retain their original organization.

dG•dT and rG•rU ‘wobble’ mispairs in DNA and RNA transiently form base pairs with Watson–Crick geometry via tautomerization and ionization with probabilities that correlate with misincorporation probabilities during replication and translation.

tRNAs contain many chemical modifications that regulate their function. Integrating smFRET and cryo-EM approaches, this work demonstrates that m¹G37 in tRNA^ProL stabilizes its conformation in the ribosomal P site in a manner that suppresses mRNA frameshifting and ensures translation fidelity.

Cytosine modifications within genomic DNA can serve as important epigenetic markers, but sequencing them at single-base resolution requires chemical modification-selective C-to-T code conversion with potential complex analysis. Now an unnatural base pair enables the sequencing of an epigenetic modification—5-formylcytosine—at single-base resolution within a Sanger sequencing format.

Pol ι forms Hoogsteen base pairs with the incoming nucleotide. Here, the authors use time-lapse X-ray crystallography to show that Hoogsten base pairing is maintained within the pol ι active site throughout the nucleotide incorporation reaction.

Replicative errors contribute to genetic diversity needed for evolution but in high frequency lead to genomic stability. Here, NMR is used to show via a kinetic model that DNA dynamics can determine the misincorporation of A•G and A•8OG mismatches.

The authors discover a homeostatic process termed interstasis, in which an increased concentration of proteins within RNA–protein condensates induces the sequestration of their own mRNAs.

A high-throughput assay that introduces mismatched base pairs into the DNA sequence shows that mismatches can increase transcription factor binding affinity by prepaying some of the energetic cost of distorting the DNA.

m⁶A RNA post-transcriptional modification changes RNA hybridization kinetics. Here the authors show that the methylamino group can adopt syn-conformation pairing with uridine with a mismatch-like conformation in RNA duplex. They also develop a quantitative model that predicts how m6A affects the kinetics of hybridization.

The results of the Fifth RNA-Puzzles contest highlights advances in RNA three-dimensional structure prediction and uncovers new insights into RNA folding and structure.

Topoisomerase 2 (Top2) is known to resolve DNA topological stress through double strand breaks (DSBs), yet Top2 inhibition has been reported to result in a significant amount of single-strand breaks (SSBs). Here the authors develop CC-seq—a method that allows direct mapping of both Top2-linked SSBs and DSBs—and reveal a significant impact of primary DNA sequence on Top2 directed cleavage.

Alterations in DNA methylation patterns are known as predictors of cancer diagnosis. Here, the authors develop a method to analyze both symmetric- and hemi-methylated regions in plasma cell free DNA and show its utility in detecting both liver and brain cancer.

DNA is found in a dynamic equilibrium between standard Watson-Crick (WC) base pairs and non-standard Hoogsteen (HG) base pairs. Here the authors describe the influence of echinomycin and actinomycin D ligands binding on the HG-WC base pair dynamics in DNA.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

The authors find subtype-specific influenza cross-reactivity patterns, including rapid declines for A(H3N2) within 6 years, sustained responses for A(H1N1)pdm09 and increased cross-reactive responses in humans after repeated A(H3N2) exposure.

The Strand-seq method independently sequences each parental strand of template DNA from single proliferating cells. It can be used to detect sister chromatid exchange and other chromosomal abnormalities at high resolution and to correct contig misorientations in genome assemblies, with potential for strand-inheritance and haplotyping studies.

The authors present the crystal structure of the MTR1 ribozyme that transfers the methyl group from O⁶-methylguanine to an adenine N1 in the target RNA and propose a catalytic mechanism based upon proximity, orientation and general acid catalysis.

Excited conformation state of biomolecule is transient and high-energy conformation state. Here the authors use NMR spectroscopy and computational modeling to reveal the 3D structure of HIV-1 TAR RNA excited conformational state.

The transcription factors TCF1 and LEF1 promote self-renewal and regulatory functions in B-1a cells.

Crystal structures of the ribozyme SAMURI reveal the alkyltransferase mechanism and show N³-modified adenosine and dealkylated cofactor in the active site, allowing for a comparison with riboswitches that bind S-adenosylmethionine but do not catalyze methyl transfer.

Adult stem cells often reside in specialized niches that they exit upon injury. Here they show that in Drosophila, after damage the gut-associated trachea produces the PDGF-VEGF-related ligand Pvf1, which acts as a guidance cue directing ISC migration toward injury sites.

CLEM-Reg automates the three-dimensional alignment of volume correlative light and electron microscopy datasets by leveraging probabilistic point cloud registration techniques for fast and accurate results across diverse datasets.

Mutagenic lesions such as those that give rise to cancer frequently segregate—unrepaired—during cell division, resulting in phasing of multiple alleles across generations of daughter cells and consequent tumour heterogeneity.

EpiGBS (epi-genotyping by sequencing) constructs de novo references using reduced representation bisulfite sequencing followed by variant calling and methylation detection.

Lu et al. perform systematic functional analyses using data from the TRACERx cohort of patients with non-small-cell lung cancer and delineate how FAT1 regulates homologous recombination repair, chromosomal instability and whole-genome doubling with distinct mechanisms.

The twister ribozyme is a recently discovered self-cleaving RNA that has wide distribution in bacteria and eukaryotes. A crystal structure of a twister ribozyme reveals a double-pseudoknot core that positions a conserved guanine near the scissile phosphate where it participates in general acid-base catalysis.

In Myeloiddysplastic syndromes, CEBPA mutations are linked to disease progression and AML. Here, the authors use somatic reprogramming and genome editing to generate isogenic cell lines from an MDS patient, identifying CEBPA bZIP domain disruption as causative for disease progression.

Turajlic and colleagues assess longitudinal antibody and cellular immune responses against SARS-CoV-2 variants of concern in patients with cancer, following either recovery from SARS-CoV-2 infection or vaccination, in two back-to-back reports from the CAPTURE study.

The secondary structure of miRNA precursor sequences is known to affect processing by DICER-like proteins. Here Rojas et al. show that additional sequence features also play a regulatory role in plants with nucleotide identity at unpaired positions substantially impacting processing efficiency.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

FIKK effector kinases underwent rapid evolutionary expansion and are a druggable target in Plasmodium falciparum.

Rev1 is a specialized translesion synthesis DNA polymerase involved in the bypass DNA damage during DNA replication. Here, the authors determine the structural basis for preferential incorporation of dCTP by Rev1 during bypass of DNA damage.

Profiling of human DNA polymerase Polε and Polα demonstrates their roles in leading and lagging strand DNA synthesis, and their independent measures allowed accurate predictions of replication dynamics and effects of transcription.

The crystal structure of the methyltransferase ribozyme MTR1 reveals a cofactor-binding site reminiscent of purine riboswitches and suggests a catalytic mechanism involving nucleobase protonation, resulting in accelerated methyl transfer rates.

A study reports on the DNA methylation dynamics during embryogenesis in marsupials, showing that these differ from those occurring during embryogenesis in eutherian mammals.

The authors present an extensive profile of host transcriptional respones to a diverse group of pathogens and allergens. In doing so, they identify TH1, type I IFN, TH17, and TH2 responses, that underlie each immune response in both the blood and lung, which represents a global profile of host-pathogen immune responses.

Hoogsteen (HG) base pairs occur transiently within DNA and exhibit altered non Watson–Crick (WC)-pairing geometries with the potential to govern sequence-dependent DNA processes. Here, Alvey et al.show that HG base pairing occurs within diverse sequence contexts and define the energetic landscapes that favour WC-to-HG transitions.