Review Articles

In this Review, the authors consider the functions of key clock transcription factors and the epigenetic regulatory mechanisms that direct circadian gene expression in mammalian cells.

Clock proteins are controlled by multiple post-translational modifications during the circadian cycle. In this Review, the authors examine how post-translational modifications influence the stability, interactions and activity of mammalian clock proteins and how they contribute to proper clock function or are altered in circadian disorders.

This review explores the molecular basis of metabolic and gene-expression oscillations in the yeast Saccharomyces cerevisiae and describes how they relate to other biological time-keeping mechanisms, such as circadian rhythms.

This Review examines the molecular mechanisms underlying the plant circadian clock, highlighting the functions of transcriptional circuits and post-translational regulation in timing and describing how clock components integrate and respond to environmental signals.

In this Review, the authors discuss recent advances in understanding how post-translational modifications of the RNA polymerase II C-terminal domain (CTD) regulate transcription and RNA processing events and control gene expression.

Numerous recent crystal and cryo-EM structures have greatly advanced understanding of the functional mechanisms of neurotransmitter-gated ion channels. This Review discusses the structural basis of activation and desensitization mechanisms in glutamate and cysteine-loop receptors.

ABC transporters use ATP hydrolysis to translocate substrates across cell membranes. Kaspar Locher reviews the mechanistic diversity of ABC transporters, as has emerged from recent structural studies, and discusses future directions for investigation of ABC-transporter-catalyzed reactions.

The synaptonemal complex (SC) connects homologous chromosomes in meiotic prophase, thus promoting genetic exchange and ensuring accurate chromosomal segregation at anaphase. In this Review, the authors discuss the structural organization of the SC and how its assembly, maintenance and disassembly are regulated in yeast and metazoans.

In this Review, the authors discuss emerging mechanisms of how the replication machinery of mammalian cells overcomes replication-fork obstacles, thus ensuring faithful genome duplication.

A comprehensive review of the discovery and molecular dissection of the eukaryotic ribosome-associated quality-control pathway for degradation of nascent proteins arising from interrupted translation.

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.

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 ribosome is a complex molecular machine that is central to protein synthesis. This Review highlights the various roles of noncoding RNAs during the different steps of ribosome biogenesis and discusses the consequences for ribosome function.

RNA interference (RNAi) is a process by which small noncoding RNAs direct molecular machinery to silence gene expression. In this Review, Ipsaro and Joshua-Tor discuss the mechanisms and structures that govern RNAi in higher organisms.

Recent structural progress on prokaryotic and eukaryotic Argonaute proteins is reviewed here, along with the insights obtained into guide and target binding and target cleavage. Comprehensive phylogenetic analyses lead to a map of Argonaute's evolutionary paths, relating structural features and physiological roles.

Ubiquitin E3 ligases catalyze the final step of the ubiquitination cascade, promoting the transfer of ubiquitin from the E2 to the substrate target. Recent structural and biochemical studies have given insights in the catalytic mechanisms of all three E3 ligase classes, as discussed in this Review.

Ubiquitin and ubiquitin-like (UBL) modifications occur primarily on lysine residues of target proteins to stimulate downstream signals. This Review discusses current knowledge of lysine specificity in ubiquitin and UBL targeting, with particular focus on the systems in which a detailed mechanism of modification and downstream signaling has been validated biochemically.

DNA metabolism is regulated by the ubiquitin and SUMO modifications, but DNA also influences whether and when these modifications occur. This Review describes the mutual interactions between DNA, ubiquitin and SUMO that occur in DNA-associated processes.

Whereas the proteasome degrades individual proteins modified with ubiquitin chains, autophagy degrades many proteins and organelles en masse. A pair of ubiquitin-like proteins (UBLs), Atg8 and Atg12, regulate autophagy-mediated degradation in a manner completely distinct from that of ubiquitin in the proteasome pathway, as discussed in this Review.