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First Fluorescent Probe for TREX1 Enables Real-Time Tracking of DNA Repair and Immune Regulation in Cancer Cells
Ying Sun1, Jinghui Zheng1, Yupei Zhang1
1Beijing National Laboratory for Molecular Sciences and MOE Key Laboratory of Bioorganic Chemistry and Molecular Engineering, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
Analytical Chemistry
|June 16, 2025
Summary
Researchers developed a new fluorescent probe to track Three Prime Repair Exonuclease 1 (TREX1) dynamics in real-time. This tool reveals TREX1
Area of Science:
- Molecular Biology
- Cancer Research
- Immunology
Background:
- Three Prime Repair Exonuclease 1 (TREX1) is a key 3' exonuclease in human cells.
- TREX1 plays critical roles in autoimmune regulation and cancer immunity.
- Existing methods are insufficient for real-time tracking of endogenous TREX1 in living cells.
Purpose of the Study:
- To develop a novel molecular tool for quantifying TREX1 activity and dynamics in living cells.
- To investigate the subcellular localization and real-time dynamics of TREX1 in normal and cancer cells.
- To explore TREX1 expression patterns in tumor tissues and their relation to cancer immunity.
Main Methods:
- Development of a dual-modified DNA fluorescent probe (Probe-TREX1).
- Live-cell imaging to track TREX1 activity and subcellular localization.
- Quantification of TREX1 levels in tumor and adjacent non-tumor tissues.
Main Results:
- Probe-TREX1 enables rapid quantification and live-cell imaging of TREX1 activity.
- TREX1 levels are comparable or higher in the nucleus than in the cytoplasm of normal and cancer cells.
- Anticancer drug stimulation leads to rapid increases in nuclear TREX1, particularly in euchromatin.
- TREX1 expression is lower in specific tumor tissues (hepatoblastoma) compared to adjacent non-tumor tissues.
Conclusions:
- The developed Probe-TREX1 is a valuable tool for studying TREX1 dynamics and functions.
- TREX1 plays a significant role in the nucleus, especially under anticancer drug treatment.
- TREX1's complex and varied roles in DNA repair and immune response across different tumor types warrant further investigation.
- This tool has potential applications in evaluating and improving cancer therapies.
