DNA lesions that persist in mitosis threaten genome stability. These lesions recruit TOPBP1-CIP2A, a complex crucial to tether and process damaged DNA on mitotic chromosomes. Importantly, CIP2A is syn...

Lebrec et al. present a FRET-based cGAS reporter and show that cGAS activation by genotoxic stress is rare and uncoupled from micronuclei. The study implicates R-loop structures and subtypes of chroma...

Li et al. present cryo-EM structures of the ATR–ATRIP complex bound to the ATR-activating domains of TOPBP1 and ETAA1; these reveal distinct binding modes and allosteric mechanism of activation for TO...

This paper introduces breakage–replication/fusion, a genomic rearrangement process underpinning three patterns of copy-number gains found in cancer and other diseases.

DNA damage can lead to cell death. Here, the authors show that a simple cut on either strand of DNA can inactivate bacterial chromosome replication. Surprisingly, only a core set of recombination prot...

DNA damage threatens genome stability, but its dynamics in living systems remain difficult to track. Here, the authors engineer MCPH1-based protein probes that specifically recognize γH2AX, enabling r...

Protein-protein interactions (PPIs) drive virtually all biological processes, yet most PPIs have not been identified and even more remain structurally unresolved. We developed a two-step computational...

Genome alterations arise from inaccurate DNA repair, accumulating into distinct mutational signatures. Here, we investigate the role of every genomically encoded gene in double-strand break (DSB) repa...

Perturbed DNA replication can lead to incompletely replicated DNA when cells enter mitosis and can interfere with chromosome segregation. Cells therefore require mechanisms to resolve these lesions du...

How cells ensure that they enter mitosis after completing replication of their genome is not fully resolved. Sobkowiak et al. describe a checkpoint involving REV7. This checkpoint has mechanistic similarities to the spindle anaphase checkpoint mediated by…

Here the authors reveal how telomeres signal mitotic stress. A key protein network alters their structure exposing telomere ends to signal mitotic stress, ultimately triggering a controlled DNA damage...

The WEE1 kinase negatively regulates CDK1/2 to control DNA replication and mitotic entry. Genetic factors that determine sensitivity to WEE1 inhibitors (WEE1i) are largely unknown. A genome-wide inser...

Tumor cells upregulate compensatory buffering genes following tumor suppressor loss. These genes may represent new synthetic lethal partners that could be harnessed therapeutically.

Schmid and Walter train a classifier that discerns functionally relevant structure predictions in proteome-wide protein-protein interaction (PPI) screens using AlphaFold-Multimer, and they use this co...

The University of Cologne is one of the oldest and largest universities in Germany. With its six Faculties covering a broad spectrum of disciplines and its i...

DNA replication is essential to life and ensures the accurate transmission of genetic information, which is significantly disturbed during cancer development and chemotherapy. While DNA replication is...

Extrachromosomal DNA (ecDNA) are circular DNA bodies that play critical roles in tumor progression and treatment resistance by amplifying oncogenes across a wide range of cancer types. ecDNA lack cent...

The Center for Epigenetic Cell Memory (EpiC) is a new Center of Excellence that will be established based on funding by the Danish National Research Foundation.

Social DNAing Webinar Series, sponsored by the Cancer Genomics and Epigenomics Program at Columbia University, aims to provide a virtual meeting room for the genomic instability community worldwide.

Rudalska et al. describe a novel class of p38α inhibitors with increased target residence time. They explore the drugs’ specificity, pharmacokinetics and toxicity profile and show that they are effica...

In this study, the authors show that DNA-damage-mediated transcriptional stress induces NF-κB through IRAK1, allowing damaged cells with impaired transcription to initiate an inflammatory response wit...

Maintaining genome integrity is an essential and challenging process. RAD51 recombinase, the central player of several crucial processes in repairing DNA and protecting genome integrity, forms filamen...

NAR Cancer is pleased to partner with the high-visibility Social DNAing webinar series, hosted by Columbia University, to present their 5th anniversary virtual

Abstract. Poly(ADP‐ribose) polymerase (PARP) inhibitors (PARPis) are currently used to treat BRCA1/2 mutant cancers. Although PARPi sensitivity has been at

Abstract. Poly(ADP‐ribose) polymerase (PARP) inhibitors (PARPis) are currently used to treat BRCA1/2 mutant cancers. Although PARPi sensitivity has been at

Aneuploidy is a hallmark of cancer and developmental disorders such as Down syndrome. Understanding how cells accomplish faithful chromosome segregation and how chromosomal instability (CIN) impacts …