Search

For several decades the MCM2-7 proteins, the core of the DNA replicative helicase, eluded detection at DNA replication sites. Here, the authors solve this conundrum by gene editing, which enables visualization of replication dynamics in living cells.

Super-resolution microscopy demonstrates how changes in the 3D organization of chromatin protect DNA against excessive degradation following damage.

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.

DNA damage arising from replication stress is well studied, but the effect of mitotic errors on genome integrity is less understood. Here the authors knock down 47 mitotic regulators and record how they impact on DNA breakage events, providing a resource for future studies on the relation between cell division and genome integrity.

Spies et al. report that 53BP1 nuclear bodies restrain duplication of under-replicated DNA until the late S phase, thus promoting RAD52-mediated repair of these lesions.

Intrinsically disordered proteins can phase separate from the soluble intracellular space. Here the authors show that the nucleic acid-mimicking biopolymer poly(ADP-ribose) (PAR) nucleates intracellular liquid demixing and orchestrates the earliest cellular responses to DNA breakage.

A new study reveals that 53BP1 influences high-fidelity homology-directed repair by showing that its depletion in the presence of increasing DNA-damage levels triggers a shift from RAD51-dependent gene conversion, an error-free process, to RAD52-mediated single-strand annealing, which is mutagenic.

DNA damage induces silencing of ribosomal RNA (rRNA) transcription. Stucki and colleagues reveal that rRNA silencing is an ATM-dependent pan-nuclear response to irradiation, in which the nucleolar protein Treacle targets DNA-damage protein NBS1 to nucleoli.

A new study reports that androgen signaling induces DNA double-strand breaks and TMPRSS2-ERG rearrangements through androgen receptor–mediated recruitment of topoisomerase 2B. These findings shed light on the generation of the most common fusion oncogene in human cancer.

Cyclin D1 is one of the drivers of the cell cycle, and its deregulation may promote the development of tumours. Surprisingly, this protein also mediates the repair of damaged DNA, a mechanism that commonly prevents cancer. See Letter p.230

Modifications of DNA-associated histone proteins maintain genome integrity. On damage to DNA, phosphorylation of histone H2A.X determines whether repair is justified or if the damaged cell must die.

Chromosomal breaks destabilize the genome and can cause developmental defects and diseases such as cancer. New work suggests that, shortly after DNA damage, dissociation of the histone binding protein HP1β from chromatin facilitates restoration of genome integrity.

Cellular senescence, the permanent state of cell-cycle arrest, is emerging as an intrinsic barrier against tumorigenesis and a mechanism contributing to organismal ageing. Unexpected findings now identify multiple secreted inflammatory cytokines, their cognate receptors and positive-feedback loops with corresponding transcription factors, as key mediators of both oncogene-induced and replicative senescence.

Signalling by ubiquitin, SUMO and other ubiquitin-like modifiers (UBLs), and crosstalk between these modifications, underlies cellular responses to DNA double-strand breaks (DSBs). Important insights have been gained into the mechanisms by which ubiquitin and UBLs regulate protein interactions at DSB sites to enable accurate repair in mammalian cells, thereby protecting genome integrity.

The tumour suppressor FBW7 is the substrate recognition component of the SCF-type ubiquitin ligase that degrades several proto-oncogenes, including MYC and cyclin E. How do the numerous cancer-associated mutations inFBW7and its substrates contribute to tumorigenesis?

Replication perturbation causes replication fork reversal (remodelling). Recent studies have visualized replication forks in metazoan cells and identified fork remodelling factors, showing fork reversal to be a global and regulated process with potential effects on replication termination, genome stability and the DNA damage response.