DNA end configurations dictate synaptic complex formation during NHEJ-mediated end bridging
Chenyang Zhang1, Weiwei Jin2, Yuhao Jiang1
1Institute of Molecular and Translational Medicine (IMTM), and Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, China.
Nature Communications
|January 16, 2026
Summary
DNA end configuration dictates non-homologous DNA end joining (NHEJ) synapsis. Microhomology enhances complex formation, influencing DNA repair efficiency and fidelity.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Non-homologous DNA end joining (NHEJ) repairs DNA double-strand breaks (DSBs) in vertebrates.
- Synapsis, the bridging of broken DNA ends, is crucial for NHEJ.
- The influence of diverse DNA end configurations on synapsis is poorly understood.
Purpose of the Study:
- To investigate how DNA end configurations affect NHEJ synapsis.
- To determine the role of microhomology and XLF in synaptic complex formation.
Main Methods:
- Single-molecule Förster Resonance Energy Transfer (smFRET) was employed.
- Analysis of synaptic complex formation with varying DNA end configurations.
Main Results:
- DNA end configurations decisively influence synapsis pathway choice.
- 3-nucleotide (nt) microhomology significantly enhances close synaptic (CS) complex formation by Ku70-Ku80 (Ku) and XRCC4-Ligase IV (X4L4), even without XLF.
- XLF promotes CS formation but is nonessential with 3-nt microhomology.
Conclusions:
- DNA end configurations are pivotal regulators of NHEJ synapsis.
- Microhomology enhances NHEJ synapsis by promoting CS complex formation.
- Findings have implications for NHEJ repair efficiency and fidelity.
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