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Updated: Jan 10, 2026
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Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
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Identification and Characterization of eccDNA in HepG2 Cells Under DOX-Induced DNA Damage
Jinyuan Zhang1, Yuguo Li1, Weijie Chen1
1School of Life Sciences and Engineering, Southwest Jiaotong University, Chengdu 610031, China.
International Journal of Molecular Sciences
|November 27, 2025
Summary
DNA damage increases extrachromosomal circular DNA (eccDNA) in liver cancer cells. These eccDNAs, particularly mobile enhancer eccDNAs (ME-eccDNAs), show altered chromatin and gene expression, impacting cancer progression.
Area of Science:
- Genomics
- Cancer Biology
- Epigenetics
Background:
- Extrachromosomal circular DNA (eccDNA) plays a role in cancer development.
- Mechanisms of eccDNA regulation under DNA damage in cancer are not well understood.
Purpose of the Study:
- To investigate eccDNA changes and transcriptional regulation following DNA damage in hepatocellular carcinoma (HCC) cells.
- To characterize the biogenesis and chromatin features of eccDNA under genotoxic stress.
Main Methods:
- Doxorubicin-induced DNA damage in HepG2 cells.
- Circle-seq for eccDNA profiling.
- RNA-seq and ATAC-seq for gene expression and chromatin accessibility.
- Hi-C and H3K27ac ChIP-seq for enhancer activity analysis.
Main Results:
- DNA damage significantly increased eccDNA number, length, and density.
- Gene expression on eccDNA correlated positively with eccDNA copy number post-damage.
- eccDNAs originated from hypomethylated, low GC content regions.
- Mobile enhancer eccDNAs (ME-eccDNAs) showed enhanced chromatin interactions and H3K27ac enrichment.
Conclusions:
- DNA damage drives eccDNA biogenesis and alters their transcriptional regulatory functions in HCC.
- ME-eccDNAs emerge as key players in DNA damage response and cancer progression.
- This study provides a systematic elucidation of DNA damage-induced eccDNA mechanisms in liver cancer.
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