Abstract
Extrachromosomal circular DNA (eccDNA) is a type of double-stranded circular DNA that is derived and free from chromosomes. It has a strong heterogeneity in sequence, length, and origin and has been identified in both normal and cancer cells. Although many studies suggested its potential roles in various physiological and pathological procedures including aging, telomere and rDNA maintenance, drug resistance, and tumorigenesis, the functional relevance of eccDNA remains to be elucidated. Recently, due to technological advancements, accumulated evidence highlighted that eccDNA plays an important role in cancers by regulating the expression of oncogenes, chromosome accessibility, genome replication, immune response, and cellular communications. Here, we review the features, biogenesis, physiological functions, potential functions in cancer, and research methods of eccDNAs with a focus on some open problems in the field and provide a perspective on how eccDNAs evolve specific functions out of the chaos in cells.
Highlights
EccDNA refers to a type of double-stranded circular DNA that is derived and free from chromosomes
According to the size and origin, Extrachromosomal circular DNA (eccDNA) can be categorized into mitochondria DNAs, episomes, double minutes (DMs) (100kb∼3 mega bases (Mb)), telomeric circle (t-circles), small polydispersed circular DNA (100bp∼10 kb), and microDNA (100–400 bp) (Wang M et al, 2021).Some studies revealed that episomes can be polymerized into DMs in cancer cells suggesting the possibility that one type of eccDNA can be transformed to others by polymerization or fragmentation with subsequent recircularization (Wahl et al, 1984; Carroll et al, 1988)
Extracellular free eccDNAs are more stable than linear cell-free DNAs and have been detected in cancer tissues and peripheral blood of cancer patients (Kumar et al, 2017), suggesting the potential applying them as a novel type of biomarkers in liquid biopsy for the early detection of diseases, the monitoring of drug treatment response, and cancer survival
Summary
EccDNA refers to a type of double-stranded circular DNA that is derived and free from chromosomes. A recent study supported an even distribution model in drug-induced apoptosis cells (Wang Y et al, 2021).
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