Extrachromosomal DNA (ecDNA)
ecDNA (Extrachromosomal DNA): Small, circular DNA fragments found in cancer cells that amplify oncogene activity, driving tumor growth and resistance to chemotherapy.
CHK1 serves as a critical DNA damage response protein primarily found in cancer cells with extrachromosomal DNA. When inhibited, it triggers selective destruction of these cancer cells, presenting a promising avenue for precision-targeted cancer treatment strategies.
Why in News
- New studies in Nature reveal how ecDNA drives cancer growth and drug resistance.
- Findings challenge Mendel’s laws of genetics, particularly the law of independent assortment.
What is ecDNA?
- Definition: Small, circular DNA fragments separated from chromosomes, floating in the nucleus.
- Formation:
- Caused by DNA damage (e.g., chromothripsis or replication errors).
- Contains multiple copies of oncogenes, which promote tumor growth.
- Prevalence:
- Present in 40% of cancer cell lines and up to 90% of brain tumor samples.
- Increases after treatments like chemotherapy.
Role of ecDNA in Cancer
- Promotes Tumor Growth: Amplifies oncogene expression by forming hubs within the nucleus.
- Drug Resistance: Oncogenes transcribed from ecDNA are 4x more active than from chromosomal DNA.
Violation of Mendel’s Law
- Normal genes follow Mendel’s independent assortment during cell division.
- ecDNA Clustering: Passed in clusters during cell division, allowing cancer cells to preserve favorable genetic combinations (termed the “jackpot effect”).
Vulnerability of ecDNA-driven Cancer
- ecDNA creates stress on cellular machinery, leading to DNA damage.
- Cancer cells rely heavily on CHK1 protein for repair.
- Potential Therapy: Drug BBI-2779 blocks CHK1, selectively killing ecDNA-dependent cancer cells and reducing tumor size.
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Source: The Hindu