Key Findings:
- Dynamic and Multi-Protein Nature of NHEJ Synapsis: NHEJ synapsis is highly dynamic and involves multi-protein assemblies that facilitate the precise alignment of broken DNA ends. Single-molecule studies, such as smFRET, reveal that this process is tightly regulated, with deficiencies potentially causing chromosomal translocations and genomic instability, as seen in radiation-induced damage models.
- Role of Single-Molecule Techniques: smFRET and other single-molecule methods have enabled real-time observation of synapsis mechanisms, uncovering how proteins mediate end-to-end bridging. These techniques demonstrate that synapsis efficiency depends on molecular interactions that can be disrupted in disease contexts, such as cancer or radiation exposure.
- Coupling with Other NHEJ Steps: The review identifies that synapsis is closely coupled with subsequent steps in NHEJ, such as end processing and ligation. This integration ensures coordinated repair but may introduce vulnerabilities under stress, like genotoxic conditions, where errors accumulate.
Significance:
The insights from single-molecule studies of NHEJ synapsis are crucial for advancing DNA repair research and therapeutic applications. Understanding the molecular mechanisms helps elucidate how DSB repair failures contribute to diseases like cancer, as deficiencies in synapsis are linked to chromosomal abnormalities observed in radiation-induced damage (e.g., from cardiac CT scans or cancer therapies) . This knowledge could inform targeted therapies to enhance repair fidelity, potentially reducing risks from genomic instability. Additionally, the review's focus on techniques like smFRET highlights their role in probing fundamental biological processes, with implications for developing new diagnostic tools or radiation-sensitizing agents in oncology. Overall, this work underscores the importance of synapsis in maintaining genomic integrity and opens avenues for interdisciplinary research in biophysics and biomedicine.
The work entitled “
Single-Molecule Techniques in Studying the Molecular Mechanisms of DNA Synapsis in Non-Homologous End-Joining Repair”was published on
Biophysics Reports (published on Mar. 2025).
DOI:
10.52601/bpr.2024.240043