# Ku70/Ku80 threading on DNA ends enables APLF bridging of breaks in single-molecule study

- Published: 2026-11-05 00:57 UTC
- Section: Life & Health › Biology & biochemistry
- Tags: APLF, Ku70/Ku80 heterodimer, non-homologous end joining, synapsis of DNA ends, double-strand break repair, mass photometry, atomic force microscopy, optical tweezers, magnetic tweezers, lncRNA NIHCOLE
- URL: https://realtech.media/news/rt-c5e3653ecb6c0f8875ccf460_ku70_ku80_threading/

**Oxford and Madrid groups showed that APLF bridges DNA ends only when at least two Ku70/Ku80 heterodimers are threaded onto each end, which limits bridging to DNA-bound Ku.**

![Ku70/Ku80 threading on DNA ends enables APLF bridging of breaks in single-molecule study](https://thumb.wikimedia.org/wikipedia/commons/thumb/0/0f/Cluster_of_PAOs.jpg/1920px-Cluster_of_PAOs.jpg?utm_source=commons.wikimedia.org&utm_campaign=imageinfo&utm_content=thumbnail)
*BJMWW, Wikimedia Commons, CC BY 4.0*

A team from the University of Oxford, the Centro Nacional de Biotecnología (CNB-CSIC) and the Spanish National Cancer Research Center (CNIO) in Madrid has described how the protein APLF brings together the two ends of a DNA double-strand break. The study was published on 3 November 2026 in Nature Communications; the corresponding authors are Fernando Moreno-Herrero and Philipp Kukura [1]. The authors combined mass photometry, atomic force microscopy, and magnetic and optical tweezers [1].

## The synapsis problem

Repair of double-strand breaks by non-homologous end joining requires synapsis, the bringing together of DNA ends [1]. APLF is emerging as an important repair factor and can form synaptic bridges in the presence of the Ku70/Ku80 heterodimer [1]. Until now, only a single one-to-one interaction between Ku70/Ku80 and APLF had been reported, which, according to the authors, is fundamentally insufficient for synapsis [1]. It also remained unclear how APLF-mediated bridging of Ku70/Ku80 heterodimers is prevented where there are no breaks [1].

The single-molecule measurements showed that APLF-mediated synapsis requires threading of at least two Ku70/Ku80 heterodimers per DNA end [1]. According to the authors, this follows from the need for two poly(ADP-ribose)-binding zinc fingers in APLF to interact simultaneously with threaded, poly(ADP-ribosyl)ated Ku70/Ku80 on a single DNA [1].

## NIHCOLE and multivalency

The group also examined the long non-coding RNA NIHCOLE. They report evidence that it binds up to four Ku70/Ku80 cooperatively [1]. The authors describe this as consistent with a mechanism that raises synapsis efficiency by bridging two Ku70/Ku80 heterodimers bound on both sides of the break [1].

From these results the authors propose a model for the physiological significance of Ku70/Ku80 threading. In it, multivalency works as a regulatory mechanism that restricts APLF-mediated bridging to DNA-bound Ku70/Ku80 [1]. The results were obtained with single-molecule techniques; the model is the authors' proposal.

## Sources

1. [Nature Communications](https://doi.org/10.1038/s41467-026-78843-9)

---

Source: RealTech, realtech.media — https://realtech.media/news/rt-c5e3653ecb6c0f8875ccf460_ku70_ku80_threading/