Reviews & Analysis

Polyglutamine (polyGln) expansions induce protein misfolding and aggregation into fibrillar deposits, which are believed to underlie forms of neurodegeneration through a mechanism involving gain of toxic function. Polyalalanine expansions are now shown to differ from polyGln in kinetics of aggregation, morphology of aggregates and mechanism of toxicity.

The mechanisms guiding the substrate specificity of kinases are still poorly understood. Two recent reports provide further insights into how the epidermal growth factor receptor (EGFR) tyrosine kinase recognizes targets by identifying a new consensus motif that requires a Src-mediated priming phosphorylation.

In this Perspective, the authors discuss how recent innovations in single-molecule fluorescence approaches now permit protein dynamics to be monitored in increasingly complex biological systems and cellular environments.

Telomerase is a unique reverse transcriptase in that it repetitively uses a short piece of its RNA component as template to synthesize DNA. A new crystal structure of a part of the Tetrahymena telomerase ribonucleoprotein reveals how reverse transcription is limited to this specific template region.

Newly synthesized 60S ribosomal subunits are licensed for translation through the release of the antiassociation factor eIF6. A new study shows by cryo–electron microscopy how eIF6 eviction results from a long-range allosteric cascade that involves SBDS, the protein mutated in Shwachman-Diamond syndrome.

Cancer cells that lack telomerase activity can maintain telomere lengths that permit continued proliferation via a recombination-based pathway called alternative lengthening of telomeres (ALT). This Review summarizes recent insights into the mechanism of ALT function and how it is repressed in normal cells to permit telomere attrition that limits replication.

Transcription of telomeres generates long noncoding RNAs (lncRNAs) composed of telomeric repeat sequences (TERRA) that hybridize with telomeric DNA and are components of telomeric heterochromatin. This Perspective considers the physiological roles of TERRA in telomere homeostasis and proposes that TERRA's functions are determined by the state of its telomere targets.

Telomerase recruitment and activity are regulated by telomere-bound proteins that protect the chromosome ends. In this Perspective, the authors discuss recent advances in understanding how the interactions of shelterin and telomerase components contribute to telomere-length homeostasis.

The shelterin complex sequesters the linear ends of chromosomes and prevents telomeres from being recognized as DNA double-strand breaks. In this Review, the authors discuss the complex interactions between shelterin components and DNA damage–response factors and consider shelterin's emerging roles as regulators of genome integrity and cell fate.

Genetic mutations that compromise telomere-length maintenance give rise to a group of related human diseases called telomere biology disorders. This Review discusses the molecular functions impaired by disease-associated mutations as well as modes of inheritance and clinical manifestations.

The crystal structure of a prokaryotic proton-driven fumarate transporter, the first for the diverse SLC26 transporter family, reveals a rare transmembrane-segment topology. The opposite orientation of two short central helices leads to the formation of a dipole-mediated anion-binding site, which is made alternately accessible to either side of the membrane through the rocking movement of the core and gate domains of the transporter.

How is cellular cargo delivered at the right time and the right place, in response to the right signal? A key new piece in this fascinating biological puzzle has just been revealed.

The cellular 'alarmone' molecule ZTP accumulates when a critical cellular metabolic pathway is starved for substrate. The high-resolution structure of ZTP bound to its RNA-based sensor reveals unexpected strategies used by RNA to specifically recognize small-molecule ligands within the complex cellular mixture.

Two studies using chromosome conformation capture (3C) analyses in the Gram-positive bacterium Bacillus subtilis have revealed a global pattern of chromosome organization that originates from loading sites of the Smc–ScpAB complex. Loading Smc–ScpAB at a single genomic location is sufficient to promote genome-wide folding of DNA into a well-defined structure.

Export of effector proteins is crucial for the virulence program of the malaria parasite Plasmodium falciparum. A crystal structure of the Plasmodium vivax processing enzyme essential for protein export reveals noncanonical aspartic protease features and provides an avenue for antimalarial drug development.

Totipotency, the ability of early embryonic cells to generate a complete adult organism as well as extraembryonic tissue, is a fleeting property found only in very early embryonic cells. A breakthrough study now shows that inhibition of DNA replication–linked nucleosome assembly causes embryonic stem cells to resemble totipotent cells. Notably, inhibition of chromatin assembly stimulates reprogramming during somatic-cell nuclear transfer experiments.

Plants protect themselves from fluctuating high-light conditions by dissipating a large part of their absorbed energy as heat, in a process that requires the protein PsbS. The structure of PsbS opens new possibilities for understanding the mechanism of photoprotection in plants.