Volume 29 Issue 9, September 2022

The mechanisms by which translesion DNA polymerases mediate DNA repair are incompletely understood. A new study shows that Escherichia coli DNA polymerase IV is concentrated at the sites of arrested DNA synthesis by an interaction with SSB, the major single-stranded DNA-binding protein, specifically at stalled but not ongoing replication forks.

New cryo-EM structures of the FANCD2–FANCI complex provide insights into how phosphorylation of FANCI facilitates DNA clamping to prime the complex for monoubiquitination and recruitment of downstream factors in the Fanconi anemia pathway of DNA damage repair.

Kottur et al. present high-resolution structures of SARS-CoV-2 nsp14 N7-MTase that will aid in the development of new antivirals against this and other pathogenic coronaviruses.

The cryo-EM structure of CRL7^FBXW8 shows that CUL7–RBX1 binds FBXW8–SKP1 in an F-box-independent manner. Bridged by FBXW8–SKP1, CRL7^FBXW8 forms a multi-cullin E3 ligase complex with neddylated CUL1–RBX1, which ubiquitinates a substrate recruited to CUL7.

The cryo-EM structures reveal orphan receptor GPR119 as the receptor for LPC. The structures with biochemical and functional data highlight evidence for LPC function in glucose regulation, and provide templates for drug design targeting GPR119.

A new method for mRNA profiling of ribosome load defines the pan-genomic interplay of transcriptional and translational regulation mediated by environment-sensing HIF and mTOR pathways in kidney cancer cells, offering insights into rational therapy.

Sijacki et al. show how phosphorylation of FANCI by the ATR DNA damage kinase primes the FANCD2–FANCI clamp for ubiquitination. Phosphorylation promotes closure of the clamp, exposing a lysine for ubiquitination to initiate DNA cross-link repair.

Kane et al. show that cohesin is required for long-range, but not shorter-range, enhancer function at the Shh locus, implicating loop extrusion as a mechanism for keeping enhancer and target genes sufficiently close together for effective enhancer–promoter communication.

The authors show that histone deacetylation maintains a high density of H3K9me3 methylated histones that transmit epigenetic memory for self-propagation of heterochromatin, which is critical for preventing untimely gene expression during development.

The Braun lab shows that the conserved nuclear membrane protein Lem2 interacts with the MTREC complex of the nuclear-exosome pathway to promote recruitment and degradation of ncRNAs and meiotic transcripts at the nuclear periphery in Schizosaccharomyces pombe.

Episomal DNA silencing by Smc5/6 is a three-step process, with the first step involving Smc5/6 binding to and entrapment of the DNA, followed by recruitment of Smc5/6 to promyelocytic leukemia nuclear bodies by SLF2. The third step requires Nse2 but not its SUMO ligase activity.

Escherichia coli SSB enriches Pol IV polymerase at lesion-stalled replication forks, promoting translesion synthesis. Loss of this enrichment increases repriming of DNA synthesis, revealing a pivotal role of SSB in the pathway choice of stalled replication forks.

The AAA-ATPase Drg1 assembles at the pre-60S ribosomal particle to release the ribosomal maturation factor Rlp24. Here, single-particle cryo-EM and 3D variability analysis dynamically visualize Rlp24 release by hand-over-hand substrate translocation.