Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Apr;34(4):270-278.
doi: 10.1016/j.tig.2017.12.010. Epub 2018 Jan 9.

Discoveries of Extrachromosomal Circles of DNA in Normal and Tumor Cells

Teressa Paulsen  1 , Pankaj Kumar  1 , M Murat Koseoglu  1 , Anindya Dutta  2
Affiliations
Review

Discoveries of Extrachromosomal Circles of DNA in Normal and Tumor Cells

Teressa Paulsen et al. Trends Genet. 2018 Apr.

Abstract

While the vast majority of cellular DNA in eukaryotes is contained in long linear strands in chromosomes, we have long recognized some exceptions like mitochondrial DNA, plasmids in yeasts, and double minutes (DMs) in cancer cells where the DNA is present in extrachromosomal circles. In addition, specialized extrachromosomal circles of DNA (eccDNA) have been noted to arise from repetitive genomic sequences like telomeric DNA or rDNA. Recently eccDNA arising from unique (nonrepetitive) DNA have been discovered in normal and malignant cells, raising interesting questions about their biogenesis, function and clinical utility. Here, we review recent results and future directions of inquiry on these new forms of eccDNA.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Junctional tag
Schematic representation of eccDNA and junctional sequence genesis from linear DNA. The two ends of linear DNA get ligated and ligation event creates a new junctional sequence which is not present in parent linear DNA; The sequencing reads partially mapping to the left and right side of ligation point are the junctional sequence. Because the junctional sequence is not present in linear DNA it acts as a discriminatory feature within computer algorithms to validate that the DNA fragment was within a circular DNA molecule [27, 28, 49]. The paired end reads pairs where one read completely maps inside the body of circle and other second reads maps on the junctional sequence are used for the final validation of circular nature of the starting DNA fragment.
Figure 2
Figure 2. Examples of how eccDNA is formed
(A) Replication slippage creates a loop on the template strand through mis-priming of a dissociated polymerase at the wrong direct repeat. The loop is then excised and ligated into a circle, leaving a microdeletion on the chromosome. (B) Replication slippage creates a loop in the product strand which is then excised and ligated into a circle, but no microdeletion is left on the chromosome. An R-loop displaces the non-template strand and allows the direct repeats on the unpaired strand to form into a loop which is then excised and ligated into a circle. Alternatively (not shown), the RNA paired DNA strand could be excised, released from the RNA and ligated between direct repeats to form a circle. In either case, the gap in the chromosomal DNA is repaired by gap filling and leaves no deletions on the chromosome. (C) ODERA mechanism of eccDNA formation. Replication slippage on pairs of inverted repeats and ligation forms a single-strand circle, e.g. [54]. (D) Double strand break within a repeat region with a proximal homologous repeat sequence is repaired by homologous recombination. The small fragment forms a circle, while the chromosome suffers a microdeletion. An example of this is in [34].
Figure 3
Figure 3. Functions of eccDNA in mammalian cells
The known functions of eccDNA are listed in black text; the hypothesized roles of eccDNA are listed in grey text.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Hotta Y, Bassel A. Molecular Size and Circularity of DNA in Cells of Mammals and Higher Plants. Proc Natl Acad Sci U S A. 1965;53:356–62. - PMC - PubMed
    1. Cox D, et al. Minute Chromatin Bodies in Malignant Tumours of Childhood. Lancet. 1965;1(7402):55–8. - PubMed
    1. Radloff R, et al. A dye-buoyant-density method for the detection and isolation of closed circular duplex DNA: the closed circular DNA in HeLa cells. Proc Natl Acad Sci U S A. 1967;57(5):1514–21. - PMC - PubMed
    1. Agsteribbe E, et al. Circular DNA from mitochondria of Neurospora crassa. Biochim Biophys Acta. 1972;269(2):299–303. - PubMed
    1. Billheimer FE, Avers CJ. Nuclear and mitochondrial DNA from wild-type and petite yeast: circularity, length, and buoyant density. Proc Natl Acad Sci U S A. 1969;64(2):739–46. - PMC - PubMed

MeSH terms

LinkOut - more resources