Single-strand DNA breaks articles from across Nature Portfolio

Gene editing is still hampered by unintended genomic alterations. Here the authors propose a method for correcting heterozygous mutations that employs multiple nicks induced by Cas9 nickase and the homologous chromosome as an endogenous repair template (NICER): this rarely induces unintended genomic alterations.

An enzymatic repair system is described which repairs nicked DNA in DNA libraries, and simulations of damage and repair suggests this enzymatic repair step is beneficial for DNA data storage.

Replication stress is a cause of genome instability in cancer cells. This Review discusses strategies to increase replicative stress by inhibiting the checkpoint kinases that coordinate DNA damage response and cell cycle, as well as combination strategies with other targeted therapies.

The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.

Biochemical and cell-based assays reveal that PARP inhibitors impede the maturation of nascent DNA strands during DNA replication, and implicate unligated Okazaki fragments and other nascent strand discontinuities in the cytotoxicity of these anti-cancer compounds.

Adamowicz et al. report that toxic PARP1 activity, induced by ataxia-associated mutations in XRCC1, impairs the recovery of global transcription during DNA base excision repair by promoting aberrant recruitment and activity of the histone ubiquitin protease USP3.

Fleming and Burrows discuss similarities between a gene-regulating DNA modification and a mutagenic one, which share a common intermediate when removed through base excision repair.

Unexpected high levels of recurrent DNA single-strand break repair were detected in enhancer regions of post-mitotic neurons.

Ribonucleotides that are misincorporated into DNA during replication are removed by topoisomerase 1, which generates 3′-terminal adducts that are not amenable to DNA repair and thus compromise genome stability. A recent report by Li et al. reveals that Apn2/APE2 resolves such blocked 3′ termini, thereby suppressing topoisomerase 1–induced mutations at ribonucleotide monophosphate sites within the genome.