DNA damage response articles from across Nature Portfolio

The tumor suppressor p53 is the guardian of the genome. Here, the authors use comprehensive approaches to demonstrate that transient p53 activity induces revival stem cells to promote the regeneration of severely irradiated intestinal epithelium in mice.

Here the authors show that PARP2 drives telomere fragility by orchestrating the Break-induced replication (BIR) pathway. This promotes DNA end resection and DNA synthesis via the regulation of POLD3.

Nuclear DNA damage downstream of mitochondrial ROS is often cited to contribute to cancer initiation and aging. However, here the authors show that although H₂O₂ induces DNA mutations when produced near DNA, it does not when released by mitochondria.

Learning results in persistent double-stranded DNA breaks, nuclear rupture and release of DNA fragments and histones within hippocampal CA1 neurons that, following TLR9-mediated DNA damage repair, results in their recruitment to memory circuits.

Here, the authors characterise the zinc finger protein ZNF827 as a single stranded DNA binding protein that accumulates at stalled replication forks to activate the ATR-CHK1 pathway and engage homologous-recombination mediated DNA repair.

Eukaryotes possess several clamp loaders comprising four common subunits and a fifth subunit unique to each complex. The RFC-A–E clamp loader loads the PCNA clamp at 3′-recessed structures for DNA replication. However, swapping a single subunit, Rad24, for RFC-A yields a clamp loader that prefers the 911 clamp and 5′-recessed DNA. Three new studies reveal detailed views of the clamp loading reaction and provide insights into substrate preferences of each loader.

Understanding how cancers react to poly(ADP-ribose) polymerase (PARP) trapping on DNA is crucial to thwart PARP inhibitor resistance. A recent study finds that trapped PARP1 is removed via the ubiquitin-dependent segregase p97, and that perturbing this molecular cascade increases PARP inhibitor cytotoxicity.

Light from a lab’s windows and lamps illuminated the path to the discovery of DNA repair.