Non-homologous-end joining articles from across Nature Portfolio

Nonhomologous end joining (NHEJ), the primary pathway of vertebrate DNA double strand-break (DSB) repair, directly re-ligates broken DNA ends with minimal errors. In this study, the authors identify structural interactions of the NHEJ-specific DNA Ligase IV (Lig4) that prioritize ligation and promote NHEJ fidelity.

DNA double-strand breaks (DSBs) are highly mutagenic making them central to many pathologies. Here, the authors developed a highly sensitive sequencing approach to study DSB mutagenesis, yielding insights into mutagenic outcomes and characterising their underlying mechanisms.

Deshpande et al show that MRN nuclease-dependent processing of DNA ends in human cells occurs at sites bound by DNA-PK. Chromatin immunoprecipitation analysis of DNA-PK, MRN, and CtIP supports a sequential model of pathway choice.

Through a genome-wide CRISPR synthetic viability screen for PARP-inhibitor resistance, Chen and Ge et al. show that transmembrane nuclease NUMEN directs double-stranded DNA break repair pathway choice at the nuclear periphery.

Cryo-EM structures of human DNA-dependent protein kinase in intermediate and active states reveal the molecular mechanism of the allosteric activation of the atypical kinase complex, explaining why it is DNA dependent.

Shieldin is a newly characterized protein complex that functions downstream of 53BP1 in promoting NHEJ

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.

In a recent paper published in Cell Research, a cryo-EM structure reveals the interface between DNA-PKcs and the Ku70/80:DNA complex, together forming the DNA-dependent protein kinase holoenzyme in non-homologous DNA end joining. Insight from this structure suggests how an allosteric rearrangement of DNA-PKcs driven by Ku70/80:DNA binding regulates kinase activity in this largest member of a family of structurally homologous phosphoinositide 3-kinase-related protein kinases that includes mTOR, ATR, and ATM.

The noncoding RNA LINP1 acts as a scaffold that links Ku and DNA-PKcs and enables efficient DNA double-strand-break repair through nonhomologous end joining (NHEJ), thereby enhancing the resistance of triple-negative breast cancer cells to radiation and chemotherapies.