ArticleNature communications2026
DNA end configurations dictate synaptic complex formation during NHEJ-mediated end bridging.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- End processing in NHEJ by Polymerase λ and PNKP is coordinated during short-range synapsis.Nature communications · 2026Article
- AID self-assembly and multistranded DNA binding drive synapsis in class switch recombination.Nucleic acids research · 2026Article
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Synapsis, the physical bridging of two broken DNA ends, is a critical step in non-homologous DNA end joining (NHEJ), the primary pathway for repairing DNA double-strand breaks (DSBs) in vertebrates. While NHEJ synapsis has been well characterized using blunt-ended DNA, how diverse DNA end configurations influence synaptic complex formation remains much less clear. Here, using single-molecule FRET, we show that end configurations play a decisive role in synapsis pathway choice, with end pairing compensating for XLF in facilitating synaptic complex transitions. Notably, 3-nucleotide (nt) microhomology at DNA ends significantly enhances close synaptic (CS) complex formation mediated by Ku70-Ku80 (Ku) and XRCC4-Ligase IV (X4L4), even in the absence of XLF. Although XLF is nonessential for synapsis with 3-nt microhomology, it further promotes CS formation when present. The FRET analysis reveals that the single-stranded and double-stranded junctions of the DNA ends are in close contact within the primary CS complex, while the overhangs flip out of the duplex, potentially stabilizing the complex. These findings underscore the pivotal role of DNA end configurations in regulating synapsis and their broader implications for NHEJ repair efficiency and fidelity.
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