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This study provides insights into the chromatin-looping-dependent and chromatin-looping-independent roles of cohesin and CTCF in controlling gene regulation.

Acetylation of histone lysine residues correlates with transcription activation, but it is currently debated whether histone acetylation is a cause or a consequence of transcription. Here, the authors show how global protein acetylation remains unaltered after acute inhibition of transcription, indicating that histone acetylation is not merely a consequence of transcription.

In a quantitative proteomics approach, Mailand, Choudhary and colleagues characterize ultraviolet-regulated ubiquitylation sites and identify a role for double mono-ubiquitylation of PCNA-associated factor PAF15 in bypassing replication-blocking lesions in DNA.

Histone H2B N-terminus multisite lysine acetylation (H2BNTac) is identified as a signature of active enhancers. H2BNTac-positive putative enhancers are validated using orthogonal enhancer activity assays.

Defects in the DNA replication checkpoint can lead to genomic instability and cancer. Here the authors show that Cmr1/WDR76 participates in the DNA replication stress response and—along with several other components—defines a new cellular compartment that forms during cellular stress.

Signalling networks regulate the biology of cells and organisms in normal and disease states. Large-scale 'precision proteomics' based on mass spectrometry now enables the system-wide characterization of signalling events, including the quantitative changes of thousands of proteins and their post-translational modifications, in response to any perturbation.

Many human proteins are regulated by lysine acetylation, but the degree of acetylation at individual sites is poorly characterized. Here, the authors measure acetylation stoichiometry in the HeLa cell proteome, providing a resource to assess mechanistic constraints on acetylation-mediated protein regulation.

The MYST acetyltransferase HBO1 is a critical regulator in maintaining leukaemia stem cells, and a small-molecule inhibitor of HBO1 is developed that shows efficacy against a range of acute myeloid leukaemia cells.

The F-box DNA helicase 1 (FBH1) is implicated in suppression of homologous recombination (HR), but the precise mechanism is unclear. Here, the authors show that FBH1 can ubiquitylate RAD51, a central player in HR, and controls the subcellular localization of RAD51.

Recent technical advances are expanding our understanding of how lysine acetylation, as well as other metabolite-sensitive acylations, regulates various cellular processes. Emerging findings point to new functions for different acylations and deacylating enzymes, and clarify the intricate link between lysine acetylation and cellular metabolism.

Mother cells recycle parental MCMs and simultaneously synthesize nascent MCMs, both of which are inherited by daughter cells, in which the former are preferentially used to form active replisomes and the latter adjust the pace of replisome movement to minimize errors during DNA replication.

HDAC6 modulates acetylation at multiple lysine residues in the N-terminal intrinsically disordered region of RNA helicase DDX3X to regulate liquid–liquid phase separation and stress granule maturation.

UV-light-induced DNA damage affects RNA metabolism but the underlying signalling pathways are largely unexplored. Here, the authors show that UV light triggers p38-MK2-mediated phosphorylation of the NELF complex, promoting its release from chromatin and concurrent transcriptional elongation.

The AAA ATPase p97 (VCP) is thought to remove specific proteins from chromatin at sites of DNA damage, to allow proper repair or processing, but how p97 targets those sites was unclear. The protein DVC1 is now shown to localize to sites of replication stress and UV-light damage, and to be required for p97 recruitment. DVC1's localization to DNA damage sites requires its UBZ domain and PCNA-interacting motif but not PCNA ubiquitination. DVC1 deficiency caused retention of error-prone translesion polymerase η at foci after UV-light damage and increased mutagenesis levels.

Comprehensive analysis of changes in protein acetylation in response to lysine deacetylase inhibitors uncovers inhibitor specificities.

At the initiation of DNA double-strand break repair, a number of ubiquitylation events occur; here, the RNF8 ubiquitin E3 ligase and the ubiquitin-conjugating E2 enzyme, UBC13, are shown to primarily modify H1-type linker histones, via a K63 linkage.

A potent and selective catalytic inhibitor of p300/CBP histone acetyltransferases suppresses tumour proliferation across multiple cell lineages, illustrating the therapeutic potential of drug-like small molecules that target histone acetyltransferases.

Non-histone-lysine acetylation affects protein functions by modulating protein stability, interactions, subcellular localization and enzymatic activity and through crosstalk with other post-translational modifications. Acetylation regulates many cellular processes, such as transcription, DNA repair, signal transduction, protein folding and autophagy.