Volume 30 Issue 5, May 2023

The enzymatic activity of PARP1—which adds chains of (poly-ADP)-ribose (PAR) to proteins—initiates DNA repair by leading to more-accessible chromatin and recruitment of PAR-dependent DNA-repair proteins. New work shows that these PARP1-catalysed functions are redirected by the auxiliary factor HPF1 in cells.

Cilia — or flagella, as they are interchangeably termed — are appendage-like organelles extending from eukaryotic cells. Several recent structural studies on intraflagellar transport (IFT) trains shed light on these fascinating complexes, including their assembly mechanism, stability, cargo recruitment and evolution.

We determined the structure of the Polα–primase complex trapped in a DNA elongation state. Cryo-electron microscopy showed that primase has a role in facilitating the timely termination of primer DNA elongation by Polα by hanging on the primer–template complex.

Single-molecule live-cell imaging of the transcription dynamics in budding yeast cells revealed that the remodeling of different nucleosomes in the promoter of a gene regulates various kinetic steps of transcription. The measurements also showed that the TATA-binding protein competes with promoter-associated nucleosomes around the TATA element to activate transcription.

Here, the authors solve the cryogenic electron microscopy structure of a human primosome to shed light on the mechanism by which RNA–DNA primers are synthesized for the initiation of DNA replication and the structural basis of the primer length limitation.

In situ cryo-electron tomography reveals the molecular structure of intraflagellar transport (IFT) protein complexes and their assembly into the anterograde IFT trains that build cilia.

Here, using cryo-EM, the authors detail how the yeast co-transcriptional assembly of the large ribosomal subunit involves a quality-control checkpoint. Ribosome-assembly factors implement this checkpoint by probing the formation and ensuring the co-operative stabilization of correctly folded ribosomal RNA.

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.

Here the authors determine the cryo-EM structure of native fibrillin microfibrils and observe how inherited genetic mutations in the microfibrils contribute to disease by disrupting a regulatory TGFβ-binding site.

Here, the authors biochemically demonstrate how the Smc5/6 SMC compartment holds a DNA loop by topologically entrapping DNA in two SMC subcompartments and the kleisin compartment. This mechanism requires the Nse5/6 loader to open the neck gate before DNA entrance.

Zhang et al. describe structures, diverse function and subunit-specific pharmacology of three major GluN2C- and GluN2D-incorporated NMDA receptors known to exist in the brain.

Here, the authors solve a series of cryo-EM structures of the Swi2/Snf2 family transcription regulator Mot1 to show how this remodeler uses energy to displace the transcription initiation factor TBP from its gene promoters.

Using cryo-EM, the authors study the RecF–DNA, RecFR–DNA, RecOR–DNA and RecFOR–DNA complexes. Combining the information from these structures, they provide new insight in how the RecFOR proteins cooperate to recognize ss–ds junctions and promote bacterial recombination.

The authors solve cryo-EM structures of the alkaline pH-induced insulin receptor-related receptor (IRR), providing clues into its activation mechanism by pH.

Here, the authors use cryo-EM to study cotranslational protein folding by the eukaryotic RAC complex and its conformational dynamics on the 80S ribosome

Smith, Zentout et al. investigate the role of HPF1 in DNA repair using live-cell imaging methods and find that HPF1-dependent histone ADP-ribosylation drives early process in DNA repair, including chromatin relaxation and repair factor recruitment.

Using single-molecule transcription imaging upon perturbations to nucleosome remodelers, the transcription factor and the transcriptional machinery, Brouwer et al. reveal how remodeling of promoter nucleosomes regulates the kinetics of transcription.

Here the authors apply low-input methyl RNA immunoprecipitation and sequencing to map the N⁶-methyladenosine landscape during mouse oocyte and early embryo development. They show that RNAs derived from retrotransposons are often N⁶-methyladenosine marked and so are many genes important for the maternal-to-zygotic transition.