DNA damage checkpoints articles from across Nature Portfolio

Sae2 phosphorylation by CDK and checkpoint kinases tunes MRX nuclease activity and Rad53 phosphorylation, allowing cells to couple DNA end clipping and checkpoint attenuation to safeguard genome stability.

Break-induced replication (BIR) repairs broken DNA but can also destabilize genomes. The authors identify 33 new genes controlling BIR completion, showing that spindle assembly and spindle positioning checkpoints coordinate repair, and that nuclear pore proteins regulate BIR at multiple steps.

SLFN11 is a predictive marker of chemosensitivity that results in elevated replication stress, but how it regulates replication fork dynamics remains unclear. Here, the authors use super-resolution microscopy to determine how SLFN11 inhibits the function of RFWD3- PRIMPOL to suppress fork restart.

Transcription-replication conflicts (TRCs) promote tumor aggressiveness by affecting genome stability. Here, the authors identify ANP32E as driver of TRCs in breast cancer, causing R-loop accumulation and genomic instability, which elicit vulnerability to ATR inhibition.

SAMHD1 promotes the degradation of nascent DNA strands to protect against aberrant activation of the pro-inflammatory cGAS–STING pathway by self DNA.

The optimization and diversification of methods for manipulating the genome will enable new therapeutic solutions.

The expression of two DNA repair factors improves the recombination of single-stranded oligodeoxynucleotides with Cas9-induced double-strand breaks, facilitating precise and efficient gene editing.

DNA damage-induced histone degradation results in decreased nucleosome occupancy, which promotes homologous recombination by enhancing the dynamicity of chromatin.

DNA supercoiling and the formation of loops suppresses the ATR checkpoint and is required for proper replication of centromeric DNA.