Reviews & Analysis

Structure-specific endonucleases (SSEs) function in concert with other DNA-remodelling enzymes and cell cycle control machineries in processes such as DNA adduct repair, Holliday junction processing and the response to replication stress. As SSEs have specificity for DNA structures rather than sequence, tight regulation of their activity is important to ensure genome stability.

Planar cell polarity — the asymmetric distribution of proteins in the plane of a cell sheet — dictates the orientation of various subcellular structures and drives collective cell rearrangements. Better understanding of this conserved axis of polarity can shed light on the mechanisms of morphogenetic processes and explain the underlying causes of human birth defects.

The carboxy-terminal domain (CTD) of RNA polymerase II is a repetitive and unstructured domain that is dynamically modified by post-translational modifications, which collectively constitute the 'CTD code'. Recent studies have revealed how CTD function is also promoted by phase separation in the presence of other low-complexity domains.

In addition to membrane-bound organelles, eukaryotic cells feature various membraneless compartments, including the centrosome, the nucleolus and various granules. Many of these compartments form through liquid–liquid phase separation, and the principles, mechanisms and regulation of their assembly as well as their cellular functions are now beginning to emerge.

Insights into eukaryotic, bacterial and archaeal RNA-based regulatory systems, including microRNAs, small interfering RNAs, clustered regularly interspaced short palindromic repeats (CRISPR) RNA and small RNAs that are dependent on the RNA chaperone protein Hfq, have revealed that they achieve specificity using similar strategies. Specifically, the presentation of short 'seed sequences' within a ribonucleoprotein complex facilitates the search for and recognition of targets.

Three microtubule nucleation pathways — initiated from centrosomes, chromatin and existing spindle microtubules — contribute to the assembly of a functional mitotic spindle in animal cells to ensure accurate chromosome segregation. Recent findings have shed light on their relative contributions to building the spindle and on adaptation of the spindle to variations in cell size and shape.

Core histone proteins are deposited on chromatin during DNA replication, whereas their replication-independent variants are deposited throughout the cell cycle by specific chaperones and chromatin remodellers. This dynamic deposition of histone variants has important roles in cell fate specification and has been implicated in development and tumorigenesis.

The nuclear envelope is more than a static barrier between the nuclear and cytoplasmic compartments. It is very dynamic and undergoes extensive remodelling in response to mechanical challenges as well as during cell division, growth and differentiation.

Telomere shortening and loss of telomere protection can have a tumour-suppressive effect by mediating proliferation arrest. Ultimately, however, these processes can cause a state of extensive genome instability known as telomere crisis, which can facilitate tumorigenesis by causing oncogenic chromosomal rearrangements, including chromothripsis, kataegis and tetraploidization.

Bromodomains (BRDs) are domains found in diverse proteins that recognize acetylated Lys residues, primarily on histones. Hence, BRD-containing proteins serve as readers of protein acetylation and engage in the regulation of gene expression. Recent studies have provided new insights into the physiological roles of BRD-containing proteins and their deregulation in cancer.

Histone chaperones safeguard the chromatin template and shield histones from promiscuous interactions to ensure their proper storage, transport, post-translational modification, nucleosome assembly and turnover.

In response to steroid ligands, glucocorticoid receptor (GR) activates or represses gene expression in a highly context-specific manner. New evidence suggests that the conformation of GR is allosterically modulated by contextual signals, including DNA sequences, ligands, post-translational modifications and other transcription regulators, and that this supports the assembly of distinct transcription complexes.