Review Articles

Break-induced replication (BIR) is a crucial DNA double-strand break-repair pathway, but it also introduces mutations linked to cancer and genetic disorders. This Review discusses BIR regulation in mammalian cells, its roles in human disease and its potential uses in genome engineering.

Here, the authors comprehensively discuss the different mechanisms for origin licensing in yeast and human cells. Importantly, they present intuitive videos illustrating such mechanisms with unprecedented detail.

In this Review, the authors discuss the physiological and biophysical functions of structurally related TMC, TMEM16 and TMEM63 families, with an aim to elucidate the mechanisms that control ion channel gating and mechanisms for scrambling lipids in the lipid membranes.

Szalay et al. discuss cross-kingdom similarities and differences in 3D chromatin folding in relation to gene regulation, including in bacteria, archaea, mammals and plants. This comparison reveals certain factors as ancestral sculptors of the genome, but also that evolution tolerates considerable variety in genome organization.

Here, the authors examine and discuss the functional complexity and cellular implications of X–Y pairs, homologous genes expressed in the human sex chromosomes.

In this Review, the authors present an overview of our current understanding of the relationship between DNA methylation and three-dimensional chromatin architecture, discussing the extent to which DNA methylation may regulate the folding of the genome.

Here, the authors discuss the various roles of the HUSH transcriptional silencing complex and its dysregulation in disease.

In this Review, the authors discuss the various ways that alternative splicing sculpts the landscape of protein interactions with their partners, essentially all types of biomolecules, and the implications of alternative interactions at the molecular, cellular and disease level.

The Review provides an overview of ion-channel insecticide targets, with a focus on their mechanisms of action, and offers a perspective for structure-based development of insecticides.

In this Review, the authors present and discuss the mechanistic and functional implications of new cryo-EM structures of telomerase from different species, contextualizing the new insights in light of existing functional analyses and decades-long hypotheses and conundrums.

Here, the authors describe the composition, architecture, functions and mechanisms of the SMC (structural maintenance of chromosomes) complex Smc5/6 in chromosomal replication and repair, as well as its involvement in disease.

In this Review, the authors provide a comprehensive overview of recent structural studies of the cGAS–STING complex, discussing pertinent functional and mechanistic implications.

Amplification of oncogene expression through extrachromosomal DNA is a common feature of many cancers and is associated with poor outcomes. Hung et al. review how regulation of extrachromosomal DNA gene expression is linked to alterations in chromatin structure and changes in contacts with DNA regulatory elements.

The organization of multiple steps of the RNA life cycle in phase-separated condensates presents a framework for understanding how sequestration of RNA-binding proteins and RNAs modulates gene expression.

Sfeir and colleagues consider recent insights into the pathways that process and repair damaged mitochondrial genomes, nuclear–mitochondrial cross-talk during mtDNA stress, and links between mtDNA dysfunction and innate immunity.

Small molecules that hijack the cellular protein ubiquitination machinery to selectively degrade proteins of interest have emerged as therapeutic modalities and powerful research tools. This Review summarizes recent developments in this field, with a focus on the use of degraders as research tools.

Lauberth and Sartorelli consider and discuss recent insights into the biogenesis and function of enhancer RNAs and the key roles they play in the regulation of gene expression.

Technological advances have led to new insights into genome-wide arrangements of nucleosomes along the DNA and the folding of the chromosome fiber in nuclear space, revealing unexpected diversity.

Husmann and Gozani review the biochemical and biological activities of histone lysine methyltransferases and their connections to human diseases, focusing on cancer.

Zaware and Zhou review the current understanding of bromodomain biology and discuss the latest development of small-molecule inhibitors that target these protein domains as emerging therapies for cancer and inflammatory disorders.