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Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.

DNA ligase 1 (LIG1) finalizes eukaryotic nuclear DNA synthesis by sealing Okazaki fragments using DNA end-joining reactions. Here the authors, by studying an engineered low-fidelity LIG1, reveal that LIG1 is a highly accurate DNA ligase in vivo.

DNA replication in the human genome occurs preferentially at initiation zones (IZs). Here, the authors identify TRESLIN-MTBP as a limiting factor for replication initiation whose loading onto DNA-bound MCM defines IZs. This process establishes IZs and replication timing in human cells.

G-quadruplexes (G4s) are stable structures that can disrupt genome stability and are dissolved by helicases. Here the authors present the structure of the yeast helicase Pif1 bound to a G4 and reveal a conserved G4 interacting region.

In vitro reconstitution of translesion synthesis–mediated replication fork restart shows how DNA Pol η is recruited to bypass a CPD lesion on the leading strand in the context of the yeast replisome.

Telomeres are endogenous cellular targets of DNA ADP-ribosylation (DNA-ADPr). TARG1-regulated DNA-ADPr is coupled to lagging telomere DNA strand synthesis, and persistent DNA-ADPr, due to TARG1 deficiency, leads to telomere shortening and fragility.

In the absence of RNase H2, ribonucleotides incorporated during DNA replication can be processed by Top1. This activity is directed to the nascent leading strand, because gaps in the lagging strand would limit torsional tension.

Genetic and genomic analyses show that S. cerevisiae DNA polymerase δ extrinsically proofreads for errors by polymerase ε and itself, and demonstrate that the symmetry of replication fidelity is achieved via coordinated efforts of intrinsic and extrinsic proofreading and DNA mismatch repair.

DNA polymerases epsilon and delta, respectively, perform the majority of leading and lagging strand replication of the eukaryotic nuclear genome. Here the authors map the ribonucleotide fingerprints of the polymerases to show the special roles of polymerase delta on both strands during replication initiation and termination.

The current model for B-family DNA polymerases in archaea is one of single-subunit enzymes in contrast to the multi-subunit complexes in eukaryotes. Here the authors show that PolB1 fromSulfolobus solfataricusexists as a heterotrimeric complex in cell extracts.

CFAP20 has a key role in rescuing RNA polymerase II complexes that have arrested during DNA transcription, limiting the accumulation of R-loops and preventing collisions between the transcription and replication machinery.

A method for single-molecule imaging at high protein concentrations is presented and demonstrated in the context of DNA replication in cell extracts.

Flap Endonuclease 1 is a DNA replication and repair enzyme indispensable for maintaining genomic stability. Here the authors provide mechanistic details on how FEN1 selects for 5′-flaps and promotes catalysis to avoid large-scale repeat expansion by a process termed ‘phosphate steering’.

The termination of DNA replication involves convergence of replication forks, the completion of DNA synthesis, replisome disassembly and the decatenation of daughter DNA molecules. Recent discoveries illustrate how replisome disassembly in eukaryotes is controlled by E3 ubiquitin ligases and how this activity is regulated to avoid genome instability.

The emRiboSeq sequencing method is used to track polymerase activity genome-wide in vivo; despite Okazaki fragment processing, DNA synthesized by error-prone polymerase-α (Pol-α) is retained in vivo and comprises ∼1.5% of the genome, establishing Pol-α as an important source of genomic variability and providing a mechanism for site-specific variation in nucleotide substitution rates.

HydEn-seq, a new sequencing method that maps the distribution of ribonucleotides misincorporated by low-fidelity DNA polymerases in budding yeast, reveals unexpected strand-specific replication patterns in both nuclear and mitochondrial genomes.

Defects in DNA mismatch repair (MMR) have been linked to inherited and sporadic cancers. Here the authors demonstrate that the DNA repair protein Rad27 (human FEN1) functions in one of three redundant mispair excision pathways, where its flap endonuclease activity catalyzes mispair excision.

DNA ligase 1 finalizes nuclear DNA replication by accurately sealing nicks generated during Okazaki Fragment Maturation. Here, Williams et al employ a low fidelity DNA ligase 1 variant to study mutation rates and specificity across the yeast genome

FBH1 is a DNA helicase and ubiquitin ligase that reverses stalled replication forks and limits RAD51 association with chromatin. Here, the authors describe the biochemical requirements for DNA unwinding and fork reversal activities and a cryo-EM structure of the SCF^FBH1 complex bound to a DNA fork.

DNA sliding clamps are ring-shaped proteins that encircle DNA and harbour polymerases and other factors that promote processive DNA replication. Here the authors use X-ray crystallography, NMR and MD simulations to propose a model for a PCNA sliding mechanism that relies on short-lived polar interactions.

A large cross-population atlas of gene–environment interactions reveals how age, sex and lifestyle shape genetic effects, heritability, prediction accuracy and disease biology, with implications for personalized medicine and drug development.

KCTD10 interacts with the DNA replication machinery and the RNA polymerase complex, inducing ubiquitination and removal of the transcription machinery in the event of co-directional transcription–replication conflicts.

Here the authors present the structure of Replication Protein A (RPA) in Archaea. The RPA structure from P. abyssi has been determined in presence and absence of DNA, providing insights into the evolution of this replication factor in eukaryotes

DNA polymerases δ and ε (Pols δ and ε) are thought to be responsible for lagging and leading strand synthesis, respectively. Here the authors present evidence that Pol δ contributes to the initiation of leading strand replication in budding yeast by synthesizing DNA of both strands at replication origins.

Mammalian DNA replication relies on various helicases and nucleases to ensure accurate genetic duplication, but how these enzymes are properly directed is unclear. Here, the authors identify USP50 as a key protein for promoting ongoing replication, restarting stalled forks, maintaining telomeres, and ensuring cell survival.

The authors develop an EM-based method to directly visualize R-loops. Applying this method to transcription-replication conflicts in human and bacterial cells, they show that DNA:RNA hybrids accumulate primarily behind replication forks, and are linked to fork slowing and fork reversal.

The influence of chromatin structure on the DNA replication programme is reciprocated by replication-coupled mechanisms that re-establish chromatin on newly formed DNA. The tight coupling of these processes is essential for promoting integrity of the genome and epigenome, with possible implications for ageing and cancer.

Polymerase exclusion of ribonucleotides during DNA replication is imperfect. New data indicate that DNA polymerase ϵ incorporates into DNA ribonucleotides that are repaired by an RNase H2–dependent process and that defective repair results in replicative stress and genome instability.

In mice, a low-protein diet leads to a gut-microbiota-driven remodelling of adipose tissue towards brown fat, showing that gut microorganisms have a role in detecting and responding to a lack of protein.

Optical aberrations limit the resolution and reliability of many fluorescence microscopy techniques. Atsushi Matsuda and colleagues report a computational adaptive optics method that restores image quality and corrects aberration-related distortions without additional hardware.

The electron transfer from aluminum to hematite in a thermite reaction is investigated here using femtosecond extreme-ultraviolet spectroscopy, offering insights into charge flow in energetic materials and laying the basis for studying chemical reactions in the solid state at the femtosecond timescale.

Tissue regeneration is of great interest; however the number of times a given tissue can regenerate is unknown. Now, Eguchiet al. demonstrate that the lens of the Japanese newt—Cynops pyrrhogaster—can regenerate 18 times over a 16-year period, and that the new lenses are similar to those of control adult animals.

The replication of telomeres poses unique problems, which the cell solves through specific mechanisms that coordinate the synthesis of the leading and lagging strands at telomeres. These mechanisms integrate the conventional replication machinery, telomere maintenance systems, DNA response pathways and chromosomal organization.

Ribonucleotides are incorporated into DNA by various mechanisms, including by DNA polymerases during replication. Such ribonucleotides may have physiological functions, but their presence is typically associated with diverse structural aberrations and interferes with fundamental processes, including DNA replication, repair and transcription. Thus, efficient mechanisms of ribonucleotide removal are key to maintaining genomic integrity and functionality.

Site-directed seamless modification of bacterial artificial chromosomes is enhanced more than tenfold in efficiency by improving the counterselection step. A set of plasmids and oligonucleotide design software also make this E. coli recombineering approach markedly faster and easier.