DNA metabolism articles within Nature

The cryogenic-electron microscopy structure of the D. thermocuniculi IsrB protein in complex with its cognate ωRNA and a target DNA shows that the RNA-dominant IsrB effector complex shares a common scaffold with the protein-dominant Cas9 effector complex.

Structures of the ATP-hydrolysing RuvAB complex captured in multiple conformations provide mechanistic insights into coordinated ATPase and motor activity during DNA recombination.

CRISPR-associated transposons exploit a proofreading checkpoint to ensure high-fidelity selection of genomic sites for DNA insertion through specific recruitment of TnsC oligomers by the Cascade complex.

Cryo-electron microscopy structures of human telomerase and telomerase in complex with TPP1 provide insights into the interactions of these proteins and their activities.

Cryo-electron microscopy structures of Cas9 during mismatch cleavage provide insight into the mechanisms that control off-target effects of Cas9, which will aid in the future design of high-fidelity Cas9 variants with reduced off-target cleavage.

Endogenous formaldehyde accumulation reveals Cockayne syndrome in mice and stimulates production of the anorexiogenic peptide GDF15 in proximal tubule cells.

By developing a new eccDNA purification and profiling method, the study revealed close-to-random genomic origination, mechanism of biogenesis and function of eccDNAs. 

Structures of the Cas4–Cas1–Cas2 complex from Geobacter sulfurreducens show that a 3′-overhang in the protospacer adjacent motif is required for complex assembly and spacer insertion into the CRISPR array.

RNA transcripts stimulate homologous recombination through the formation of DR-loops, intermediate structures that contain both DNA–DNA and DNA–RNA hybrids.

Reconstitution of the activation of the MLH1–MLH3 endonuclease shows how crossovers are formed during meiosis.

Single-molecule fluorescence resonance energy transfer and real-time confocal laser tracking with fluorescence correlation spectroscopy together characterize how individual lac repressor molecules bypass operator sites while exploring the DNA surface at microsecond timescales.

Whole-genome sequencing of the strains of the Saccharomyces cerevisiae gene-knockout collection reveals the effects of the deletion of non-essential genes on genome stability.

ORBIT (origami-rotor-based imaging and tracking) is used to track the DNA rotation that results from DNA unwinding by RecBCD helicase and transcription by RNAP at a single-molecule scale and millisecond time resolution.

53BP1 and shieldin recruit the CTC1–STN1–TEN1 complex and polymerase-α to sites of DNA damage to help control the repair of double-strand breaks.

A mechanism for the unfolding of guanine-rich DNA ‘quadruplexes’ by helicases is suggested, based on the structure of a DNA-bound helicase.

Detailed structures of yeast RNA polymerase III and its initiation complex shed light on how the transcription of essential non-coding RNAs begins and allow comparisons with other RNA polymerases.

A new DNA ‘base editor’ can change targeted A•T base pairs to G•C, allowing disease-associated mutations to be corrected and disease-suppressing mutations to be introduced into cells.

The mechanism by which formaldehyde, a potent DNA and protein crosslinking agent, is generated from folate is described, with implications for the treatment of certain cancers.

Methylation at the 6 position of adenosine (m⁶A) in RNA is rapidly and transiently induced at DNA damage sites in response to ultraviolet irradiation.

Enzymes of the nucleotide salvage pathway are shown to have substrate selectivity that protects newly synthesized DNA from random incorporation of epigenetically modified forms of cytosine; a subset of cancer cell lines that overexpress cytidine deaminase (CDA) are sensitive to treatment with 5hmdC or 5fdC (oxidized forms of 5-methyl-cytosine), which leads to DNA damage and cell death, indicating the chemotherapeutic potential of these nucleoside variants for CDA-overexpressing cancers.

Structural and biochemical studies of RNA polymerase II (Pol II) assembled on DNA containing 5-carboxycytosine reveals that Pol II can sense the oxidized methylation state of DNA and transiently slows down during transcription.

In the bacterial immunity system CRISPR, spacer acquisition is facilitated near replication-termination regions.

It has long been a goal to reconstitute eukaryotic DNA replication; here a purified in vitro system from budding yeast containing 16 factors, themselves composed of 42 polypeptides, fulfils the staged process of origin-dependent initiation, including its regulation by kinases.

Crystal structure of the RNA-guided endonuclease Cas9 bound to a guide RNA and a target DNA duplex reveals how base-specific recognition of a short motif known as PAM in the DNA target results in localized strand separation in the DNA immediately upstream of the PAM, allowing the target DNA strand to hybridize to the guide RNA.

Triphosphates of hydrophobic nucleotides d5SICS and dNaM are imported into Escherichia coli by an exogenous algal nucleotide triphosphate transporter and then used by an endogenous polymerase to replicate, and faithfully maintain over many generations of growth, a plasmid containing the d5SICS–dNaM unnatural base pair.

The Tet family of dioxygenase enzymes convert 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine, which has an effect on gene expression; here the structure of NgTet1, a Tet-like protein with the same activity as mammalian Tet1, is determined, showing that NgTet1 uses a base-flipping mechanism to access 5-methylcytosine.

In vitro and in vivo, the yeast Pif1 helicase is able to unwind four-stranded G-quadruplex (G4) DNA efficiently and suppress the genomic instability that occurs at such structures; these G4 maintenance activities are conserved among evolutionarily diverse Pif1 family helicases, including human PIF1, demonstrating the importance of this activity throughout evolution.

The long-awaited structure of a telomerase holoenzyme, from Tetrahymena, has been obtained by electron microscopy; affinity labelling of subunits and modelling with NMR and crystal structures of various components allowed the identification of the catalytic core and subunit interactions, and the functional role of the subunits in telomerase processivity was enabled by performing the first reconstitution of the holoenzyme in vitro.

A bout of exercise sees methyl groups removed from metabolic genes.