Reviews & Analysis

Cryo-EM analysis reveals the mechanism by which chromatin is compacted at the centromere by the H3 histone variant CENP-N. Intriguingly, despite the structural differences between CENP-N and linker H1 histones, both appear to similarly compact higher-order nucleosome structures.

Eukaryotes possess several clamp loaders comprising four common subunits and a fifth subunit unique to each complex. The RFC-A–E clamp loader loads the PCNA clamp at 3′-recessed structures for DNA replication. However, swapping a single subunit, Rad24, for RFC-A yields a clamp loader that prefers the 911 clamp and 5′-recessed DNA. Three new studies reveal detailed views of the clamp loading reaction and provide insights into substrate preferences of each loader.

The molecular mechanisms by which a few molecules of the long non-coding RNA Xist silence genes on the entire X chromosome are poorly understood. New evidence suggests that dimeric foci of Xist seed the formation of large protein assemblies that contain a wide spectrum of proteins, such as SPEN (SHARP), CIZ1, CELF, PTBP1 and components of Polycomb repressive complexes 1 and 2. These assemblies, each of which may contain hundreds to thousands of molecules of proteins, extend spatially beyond each focus of Xist, which explains how this long non-coding RNA triggers silencing across an entire chromosome.

The class II phosphatidylinositol 3-kinases (PI3Ks) serve important roles in diverse cellular processes. The lab of Volker Haucke has now determined high-resolution structures of mouse PI3KC2α in both active and inactive conformations, elucidating the autoregulatory mechanism of class II PI3K activation.

Growing evidence suggests that many ribosome-targeting antibiotics inhibit protein synthesis context specifically, which has important implications for drug development. New work reveals the structural basis of context-specific action of the classic translation inhibitor chloramphenicol and the oxazolidinones linezolid and radezolid.

An elegant cryo-EM and biophysical study unveils the conformational changes of the E. coli MutS mismatch repair factor. This provides a nice follow-up to the recent report from the same group characterizing how MutS scans DNA without initiating repair on correctly base-paired DNA and recruits MutL upon encountering a mismatch.

Retinal photoreceptor cyclic nucleotide-gated (CNG) ion channels convert light signals to electrical signals in the eye. Their structures have been solved at ~3 Å resolution by cryo-EM; the asymmetric subunit assembly of heteromeric CNG channels produces a unique ion-permeation pathway with an unusual gating apparatus that indicates distinct subunit contributions for ligand-dependent channel activation.