circular dna


Summary: Any of the covalently closed DNA molecules found in bacteria, many viruses, mitochondria, plastids, and plasmids. Small, polydisperse circular DNA's have also been observed in a number of eukaryotic organisms and are suggested to have homology with chromosomal DNA and the capacity to be inserted into, and excised from, chromosomal DNA. It is a fragment of DNA formed by a process of looping out and deletion, containing a constant region of the mu heavy chain and the 3'-part of the mu switch region. Circular DNA is a normal product of rearrangement among gene segments encoding the variable regions of immunoglobulin light and heavy chains, as well as the T-cell receptor. (Riger et al., Glossary of Genetics, 5th ed & Segen, Dictionary of Modern Medicine, 1992)

Top Publications

  1. Abd Alla A, Cousserans F, Parker A, Jehle J, Parker N, Vlak J, et al. Genome analysis of a Glossina pallidipes salivary gland hypertrophy virus reveals a novel, large, double-stranded circular DNA virus. J Virol. 2008;82:4595-611 pubmed publisher
    ..The GpSGHV genome is a double-stranded circular DNA molecule of 190,032 bp containing 160 nonoverlapping open reading frames (ORFs), which are distributed equally ..
  2. Kanter D, Bruck I, Kaplan D. Mcm subunits can assemble into two different active unwinding complexes. J Biol Chem. 2008;283:31172-82 pubmed publisher
    ..The Mcm4/Mcm7 and Mcm4/Mcm6/Mcm7 assemblies can open to load onto circular DNA to initiate unwinding...
  3. Dahl F, Gullberg M, Stenberg J, Landegren U, Nilsson M. Multiplex amplification enabled by selective circularization of large sets of genomic DNA fragments. Nucleic Acids Res. 2005;33:e71 pubmed
    ..Eighty-nine percent of the selectors generated PCR products that hybridized to the expected positions on the array, while little or no amplification artifacts were observed. ..
  4. Stenberg J, Dahl F, Landegren U, Nilsson M. PieceMaker: selection of DNA fragments for selector-guided multiplex amplification. Nucleic Acids Res. 2005;33:e72 pubmed
    ..The PieceMaker program alleviates this problem by selecting restriction enzymes to generate suitable fragments for selection, and generating the output data required to design the selector probes. ..
  5. Du Q, Kotlyar A, Vologodskii A. Kinking the double helix by bending deformation. Nucleic Acids Res. 2008;36:1120-8 pubmed
    ..Our results suggest that strong DNA bending initiates kink formation while preserving base pairing. ..
  6. Petrova V, Chitteni Pattu S, Drees J, Inman R, Cox M. An SOS inhibitor that binds to free RecA protein: the PsiB protein. Mol Cell. 2009;36:121-30 pubmed publisher
    ..However, PsiB binds to RecA protein that is free in solution. The RecA-PsiB complex impedes formation of RecA nucleoprotein filaments on DNA. ..
  7. Sung J, Wong M, Bowden S, Liew C, Hui A, Wong V, et al. Intrahepatic hepatitis B virus covalently closed circular DNA can be a predictor of sustained response to therapy. Gastroenterology. 2005;128:1890-7 pubmed
    ..Intrahepatic HBV cccDNA and intrahepatic total HBV DNA levels at the end of therapy are superior to serum HBV DNA as surrogates of sustained virologic response. ..
  8. Benevides J, Serban D, Thomas G. Structural perturbations induced in linear and circular DNA by the architectural protein HU from Bacillus stearothermophilus. Biochemistry. 2006;45:5359-66 pubmed
    ..This model is consistent with the wide range of DNA bending angles reported in crystal structures of HU-DNA complexes. ..
  9. Bader M, Ohlebusch E. Sorting by weighted reversals, transpositions, and inverted transpositions. J Comput Biol. 2007;14:615-36 pubmed
    ..In this paper, we provide a 1.5-approximation algorithm for sorting by weighted reversals, transpositions and inverted transpositions for biologically realistic weights. ..

More Information


  1. Cohen Z, Bacharach E, Lavi S. Mouse major satellite DNA is prone to eccDNA formation via DNA Ligase IV-dependent pathway. Oncogene. 2006;25:4515-24 pubmed
    Elevated levels of extrachromosomal circular DNA (eccDNA or spcDNA) are closely associated with genomic instability and aging. Despite extensive studies, the mechanism of its generation in mammalian cells is unknown...
  2. Cohen S, Agmon N, Yacobi K, Mislovati M, Segal D. Evidence for rolling circle replication of tandem genes in Drosophila. Nucleic Acids Res. 2005;33:4519-26 pubmed
    Extrachromosomal circular DNA (eccDNA) is one characteristic of the plasticity of the eukaryotic genome. It is found in various organisms and contains sequences derived primarily from repetitive chromosomal DNA...
  3. Gao W, Hu J. Formation of hepatitis B virus covalently closed circular DNA: removal of genome-linked protein. J Virol. 2007;81:6164-74 pubmed
    ..Interestingly, PF-RC DNA, in contrast to RT-linked RC DNA, contained, almost exclusively, mature plus-strand DNA, suggesting that the RT protein was removed preferentially from mature RC DNA...
  4. Wang Y, Morse D. The plastid-encoded psbA gene in the dinoflagellate Gonyaulax is not encoded on a minicircle. Gene. 2006;371:206-10 pubmed
    ..In particular, the psbA gene is associated with DNA of roughly 50-150 kb and appears to have an unusually high complexity. ..
  5. Guo H, Jiang D, Zhou T, Cuconati A, Block T, Guo J. Characterization of the intracellular deproteinized relaxed circular DNA of hepatitis B virus: an intermediate of covalently closed circular DNA formation. J Virol. 2007;81:12472-84 pubmed
    Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is formed by conversion of capsid-associated relaxed circular DNA (rcDNA) via unknown mechanisms and exists in the nucleus of the infected hepatocyte as a minichromosome ..
  6. Cohen S, Segal D. Extrachromosomal circular DNA in eukaryotes: possible involvement in the plasticity of tandem repeats. Cytogenet Genome Res. 2009;124:327-38 pubmed publisher
    Extrachromosomal circular DNA (eccDNA) is ubiquitous in eukaryotic organisms, and has been noted for more than 3 decades...
  7. Guo Y, Li Y, Mu S, Zhang J, Yan Z. Evidence that methylation of hepatitis B virus covalently closed circular DNA in liver tissues of patients with chronic hepatitis B modulates HBV replication. J Med Virol. 2009;81:1177-83 pubmed publisher
    ..The aim of this study was to compare the methylation status of the intrahepatic covalently closed circular DNA (cccDNA) CpG island 2 and HBV replication capability...
  8. Sturm M, Roday S, Schramm V. Circular DNA and DNA/RNA hybrid molecules as scaffolds for ricin inhibitor design. J Am Chem Soc. 2007;129:5544-50 pubmed
    ..Truncated stem-loop versions of the 28S rRNA are RTA substrates. Here, we investigate circular DNA and DNA/RNA hybrid GAGA sequence oligonucleotides as minimal substrates and inhibitor scaffolds for RTA ..
  9. Hui C, Bowden S, Jackson K, Au W, Fong D, Lie A, et al. Clinical significance of intrahepatic hepatitis B virus covalently closed circular DNA in chronic hepatitis B patients who received cytotoxic chemotherapy. Blood. 2005;105:2616-7 pubmed
  10. Bochman M, Schwacha A. The Mcm2-7 complex has in vitro helicase activity. Mol Cell. 2008;31:287-93 pubmed publisher
    ..Our results show that purified Mcm2-7 acts as a helicase, provides functional evidence of a Mcm2/5 gate, and lays the foundation for future mechanistic studies of this critical factor. ..
  11. Micheletti C, Marenduzzo D, Orlandini E, Sumners D. Simulations of knotting in confined circular DNA. Biophys J. 2008;95:3591-9 pubmed publisher
    ..discrepancy due to the insufficient confinement of the equilibrium simulation or does it indicate that out-of-equilibrium mechanisms (such as rotation by packaging motors) affect the genome organization, hence its knot spectrum in P4? ..
  12. Di Giusto D, Wlassoff W, Gooding J, Messerle B, King G. Proximity extension of circular DNA aptamers with real-time protein detection. Nucleic Acids Res. 2005;33:e64 pubmed
    ..Here we report upon a property specific to circular DNA aptamers: their intrinsic compatibility with a highly sensitive protein detection method termed the 'proximity ..
  13. Takkenberg R, Zaaijer H, Menting S, Weegink C, Terpstra V, Cornelissen M, et al. Detection of hepatitis B virus covalently closed circular DNA in paraffin-embedded and cryo-preserved liver biopsies of chronic hepatitis B patients. Eur J Gastroenterol Hepatol. 2010;22:952-60 pubmed publisher
    Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) may become an important predictor for treatment outcome or long-term follow-up...
  14. Arsuaga J, Vazquez M, McGuirk P, Trigueros S, Sumners D, Roca J. DNA knots reveal a chiral organization of DNA in phage capsids. Proc Natl Acad Sci U S A. 2005;102:9165-9 pubmed
    ..These results indicate that the packaging geometry of the DNA inside the viral capsid is writhe-directed. ..
  15. Jarvius J, Melin J, Göransson J, Stenberg J, Fredriksson S, Gonzalez Rey C, et al. Digital quantification using amplified single-molecule detection. Nat Methods. 2006;3:725-7 pubmed
    ..We apply the method for sensitive detection and quantification of the bacterial pathogen Vibrio cholerae. ..
  16. Bennett M, Woolford L, Stevens H, Van Ranst M, Oldfield T, Slaven M, et al. Genomic characterization of a novel virus found in papillomatous lesions from a southern brown bandicoot (Isoodon obesulus) in Western Australia. Virology. 2008;376:173-82 pubmed publisher
    ..The discovery of BPCV2 provides evidence of virus-host co-speciation between BPCVs and marsupial bandicoots and has important implications for the phylogeny and taxonomy of circular double-stranded DNA viruses infecting vertebrates...
  17. Alsallaq R, Zhou H. Protein association with circular DNA: rate enhancement by nonspecific binding. J Chem Phys. 2008;128:115108 pubmed publisher
    ..nonspecific-binding-facilitated diffusion-controlled rate of association of a protein with a specific site on a circular DNA is derived. Nonspecific binding is modeled by a short-range attractive surface potential...
  18. Suzuki F, Miyakoshi H, Kobayashi M, Kumada H. Correlation between serum hepatitis B virus core-related antigen and intrahepatic covalently closed circular DNA in chronic hepatitis B patients. J Med Virol. 2009;81:27-33 pubmed publisher
    ..and viral status by the analysis of serum HBeAg, HBsAg, peripheral HBV DNA, and intrahepatic covalently closed circular DNA (cccDNA) in 57 chronic hepatitis B patients...
  19. Yuan C, Lou X, Rhoades E, Chen H, Archer L. T4 DNA ligase is more than an effective trap of cyclized dsDNA. Nucleic Acids Res. 2007;35:5294-302 pubmed
    ..For short dsDNA fragments, however, the population of DNA-ligase complexes at typical ATP concentrations used in DNA cyclization studies is determined to be large enough to dominate the cyclization reaction. ..
  20. Blinkova O, Victoria J, Li Y, Keele B, Sanz C, Ndjango J, et al. Novel circular DNA viruses in stool samples of wild-living chimpanzees. J Gen Virol. 2010;91:74-86 pubmed publisher
    ..Sequences encoding proteins distantly related to the replicase protein of single-stranded circular DNA viruses were identified. Inverse PCR was used to amplify and sequence multiple small circular DNA viral genomes...
  21. Zellinger B, Akimcheva S, Puizina J, Schirato M, Riha K. Ku suppresses formation of telomeric circles and alternative telomere lengthening in Arabidopsis. Mol Cell. 2007;27:163-9 pubmed
    ..However, telomeres in ku mutants are fully functional, indicating that telomerase efficiently heals ongoing terminal deletions arising from excision of the t circles. ..
  22. Sato M, Ohtsuka M, Ohmi Y. Usefulness of repeated GenomiPhi, a phi29 DNA polymerase-based rolling circle amplification kit, for generation of large amounts of plasmid DNA. Biomol Eng. 2005;22:129-32 pubmed
    ..We demonstrated that repeated RCA (at least three times) is useful for high-fidelity amplification of large amounts of plasmid DNA...
  23. Mazet Wagner A, Baclet M, Loustaud Ratti V, Denis F, Alain S. Real-time PCR quantitation of hepatitis B virus total DNA and covalently closed circular DNA in peripheral blood mononuclear cells from hepatitis B virus-infected patients. J Virol Methods. 2006;138:70-9 pubmed
    ..The specificity of the methodology was increased by prior treatment with an enzyme that digests relaxed circular DNA, and the elimination of background signals from virus adsorbed to the surface of PBMCs...
  24. Demurtas D, Amzallag A, Rawdon E, Maddocks J, Dubochet J, Stasiak A. Bending modes of DNA directly addressed by cryo-electron microscopy of DNA minicircles. Nucleic Acids Res. 2009;37:2882-93 pubmed publisher
    ..We corroborate the results of cryo-EM studies by using Bal31 nuclease to probe for the existence of kinks in 94-bp-long minicircles. ..
  25. Wang Z, Wilner O, Willner I. Self-assembly of aptamer-circular DNA nanostructures for controlled biocatalysis. Nano Lett. 2009;9:4098-102 pubmed publisher
    Two kinds of circular DNA components are generated by the hybridization of short nucleic acids with the 3' and 5' ends of single-stranded DNA chains...
  26. Briggs G, Yu J, Mahdi A, Lloyd R. The RdgC protein employs a novel mechanism involving a finger domain to bind to circular DNA. Nucleic Acids Res. 2010;38:6433-46 pubmed publisher
    ..that destabilizing either interface has a serious effect on in vivo function, even though a stable complex with circular DNA was still observed. We conclude that tight binding is required for inhibition of RecA activity...
  27. Gueudin M, Braun J, Plantier J, Simon F. HIV-1 and HIV-2 produce different amounts of 2-long terminal repeat circular DNA in vitro. AIDS. 2008;22:2543-5 pubmed publisher
    We assessed HIV-1 and HIV-2 2-long terminal repeat (LTR) circular DNA production in peripheral blood mononuclear cells, MT4-CXCR4 cells and HeLa-CXCR4-CCR5 cells in vitro, relative to the respective total amounts of HIV DNA...
  28. Johne R, Muller H, Rector A, Van Ranst M, Stevens H. Rolling-circle amplification of viral DNA genomes using phi29 polymerase. Trends Microbiol. 2009;17:205-11 pubmed publisher
    ..Recently, the bacteriophage phi29 DNA polymerase has been used for the efficient amplification of circular DNA viral genomes without the need of specific primers by a rolling-circle amplification (RCA) mechanism...
  29. Fernandes F, Pereira L, Freitas A. CSA: an efficient algorithm to improve circular DNA multiple alignment. BMC Bioinformatics. 2009;10:230 pubmed publisher
    ..alignment algorithms have been proposed to date, they all deal with linear DNA and cannot handle directly circular DNA. Researchers interested in aligning circular DNA sequences must first rotate them to the "right" ..
  30. Lutgehetmann M, Volz T, Köpke A, Broja T, Tigges E, Lohse A, et al. In vivo proliferation of hepadnavirus-infected hepatocytes induces loss of covalently closed circular DNA in mice. Hepatology. 2010;52:16-24 pubmed publisher
    Chronic hepatitis B virus (HBV) infection is maintained by the presence of covalently closed circular DNA (cccDNA), the template of viral transcription and replication...
  31. Lin L, Wong V, Zhou H, Chan H, Gui H, Guo S, et al. Relationship between serum hepatitis B virus DNA and surface antigen with covalently closed circular DNA in HBeAg-negative patients. J Med Virol. 2010;82:1494-500 pubmed publisher
    Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is responsible for viral persistence...
  32. Gillim Ross L, Cara A, Klotman M. HIV-1 extrachromosomal 2-LTR circular DNA is long-lived in human macrophages. Viral Immunol. 2005;18:190-6 pubmed
    ..Furthermore, exrachromosomal circular DNA in this cell population could be a source of persisent viral protein expression.
  33. Miles L, Agresta B, Khan M, Tang S, Levin J, Powell M. Effect of polypurine tract (PPT) mutations on human immunodeficiency virus type 1 replication: a virus with a completely randomized PPT retains low infectivity. J Virol. 2005;79:6859-67 pubmed
    ..Together, these experiments confirm that the 3' end of the PPT is important for plus-strand priming and that a virus that completely lacks a PPT can replicate at a low level. ..
  34. Humpolickova J, Stepanek M, Kral T, Benda A, Prochazka K, Hof M. On mechanism of intermediate-sized circular DNA compaction mediated by spermine: contribution of fluorescence lifetime correlation spectroscopy. J Fluoresc. 2008;18:679-84 pubmed publisher
    ..Furthermore, we show that it allows for observation of the equilibrium state transition dynamics. ..
  35. Koumandou V, Howe C. The copy number of chloroplast gene minicircles changes dramatically with growth phase in the dinoflagellate Amphidinium operculatum. Protist. 2007;158:89-103 pubmed
    The chloroplast genome of algae and plants typically comprises a circular DNA molecule of 100-200kb, which harbours approximately 120 genes, and is present in 50-100 copies per chloroplast...
  36. Amzallag A, Vaillant C, Jacob M, Unser M, Bednar J, Kahn J, et al. 3D reconstruction and comparison of shapes of DNA minicircles observed by cryo-electron microscopy. Nucleic Acids Res. 2006;34:e125 pubmed
    ..We conclude that the presence of the TATA box sequence, which is believed to be easily bent, does not significantly affect the observed shapes. ..
  37. Delelis O, Petit C, Leh H, Mbemba G, Mouscadet J, Sonigo P. A novel function for spumaretrovirus integrase: an early requirement for integrase-mediated cleavage of 2 LTR circles. Retrovirology. 2005;2:31 pubmed
    ..More generally, it suggests to reassess 2-LTR circles as functional intermediates in the retrovirus cycle and to reconsider the idea that formation of the integrated provirus is an essential step of retrovirus production...
  38. Margeridon S, Carrouée Durantel S, Chemin I, Barraud L, Zoulim F, Trepo C, et al. Rolling circle amplification, a powerful tool for genetic and functional studies of complete hepatitis B virus genomes from low-level infections and for directly probing covalently closed circular DNA. Antimicrob Agents Chemother. 2008;52:3068-73 pubmed publisher
    ..Covalently closed circular DNA (cccDNA) from liver biopsies could be amplified directly from as few as 13 copies, using RCA, followed by a ..
  39. Schmidt H, Taubert H, Lange H, Kriese K, Schmitt W, Hoffmann S, et al. Small polydispersed circular DNA contains strains of mobile genetic elements and occurs more frequently in permanent cell lines of malignant tumors than in normal lymphocytes. Oncol Rep. 2009;22:393-400 pubmed
    Small polydispersed circular DNA (spcDNA) belongs to the extrachromosomal pool of DNA and is composed of heterogeneous DNA circles...
  40. Chou Y, Jeng K, Chen M, Liu H, Liu T, Chen Y, et al. Evaluation of transcriptional efficiency of hepatitis B virus covalently closed circular DNA by reverse transcription-PCR combined with the restriction enzyme digestion method. J Virol. 2005;79:1813-23 pubmed
    Virus persistence in chronic hepatitis B patients is due to the sustaining level of covalently closed circular DNA (cccDNA) within the nuclei of infected hepatocytes. In this study, we used a modified 1...
  41. Groff Vindman C, Cesare A, Natarajan S, Griffith J, McEachern M. Recombination at long mutant telomeres produces tiny single- and double-stranded telomeric circles. Mol Cell Biol. 2005;25:4406-12 pubmed
    ..The very small circles seen here are both predicted products of telomere rapid deletion, a process observed in both human and yeast cells, and predicted templates for roll-and-spread RTE. ..
  42. Lenci I, Marcuccilli F, Tisone G, Di Paolo D, Tariciotti L, Ciotti M, et al. Total and covalently closed circular DNA detection in liver tissue of long-term survivors transplanted for HBV-related cirrhosis. Dig Liver Dis. 2010;42:578-84 pubmed publisher
    ..cccDNA should be considered a new additional diagnostic tool, also to identify patients at low risk of HBV recurrence after liver transplantation. ..
  43. Guo H, Mao R, Block T, Guo J. Production and function of the cytoplasmic deproteinized relaxed circular DNA of hepadnaviruses. J Virol. 2010;84:387-96 pubmed publisher
    ..viral DNA polymerase ought to be an essential step in the formation of hepadnavirus covalently closed circular DNA (cccDNA)...
  44. Zhang Y, Theele D, Summers J. Age-related differences in amplification of covalently closed circular DNA at early times after duck hepatitis B virus infection of ducks. J Virol. 2005;79:9896-903 pubmed
    ..We suggest that lower virus replication is due to a less rapid covalently closed circular DNA amplification, leading to lower viremias and a slower spread of infection in the liver, and that the slower ..
  45. Le Mire M, Miller D, Foster W, Burrell C, Jilbert A. Covalently closed circular DNA is the predominant form of duck hepatitis B virus DNA that persists following transient infection. J Virol. 2005;79:12242-52 pubmed
    ..These findings further characterize a second form of hepadnavirus persistence in a suppressed or inactive state, quite distinct from the classical chronic carrier state...
  46. Wong D, Yuen M, Poon R, Yuen J, Fung J, Lai C. Quantification of hepatitis B virus covalently closed circular DNA in patients with hepatocellular carcinoma. J Hepatol. 2006;45:553-9 pubmed
    This study aimed to measure the intrahepatic total hepatitis B virus (HBV) DNA and covalently closed circular DNA (cccDNA) levels in tumor and non-tumor tissues in hepatocellular carcinoma (HCC) patients...
  47. Cohen Z, Lavi S. Replication independent formation of extrachromosomal circular DNA in mammalian cell-free system. PLoS ONE. 2009;4:e6126 pubmed publisher
    Extrachromosomal circular DNA (eccDNA) is a pool of circular double stranded DNA molecules found in all eukaryotic cells and composed of repeated chromosomal sequences...
  48. Wong D, Yuen M, Ngai V, Fung J, Lai C. One-year entecavir or lamivudine therapy results in reduction of hepatitis B virus intrahepatic covalently closed circular DNA levels. Antivir Ther. 2006;11:909-16 pubmed
    ..However, the effects of these two antiviral agents on intrahepatic total HBV DNA and covalently closed circular DNA (cccDNA) are not known...
  49. Lohmann J, Stougaard M, Koch J. A new enzymatic route for production of long 5'-phosphorylated oligonucleotides using suicide cassettes and rolling circle DNA synthesis. BMC Biotechnol. 2007;7:49 pubmed
    ..Furthermore, the hairpin can be removed by cleavage with the Mly I restriction enzyme. We have named such hairpin structures "suicide cassettes". ..
  50. Cohen S, Houben A, Segal D. Extrachromosomal circular DNA derived from tandemly repeated genomic sequences in plants. Plant J. 2008;53:1027-34 pubmed
    Extrachromosomal circular DNA (eccDNA) is one characteristic of the plasticity of the eukaryotic genome. It was found in various non-plant organisms from yeast to humans...
  51. Zimmerman K, Fischer K, Joyce M, Tyrrell D. Zinc finger proteins designed to specifically target duck hepatitis B virus covalently closed circular DNA inhibit viral transcription in tissue culture. J Virol. 2008;82:8013-21 pubmed publisher
    ..In summary, designed ZFPs are able to bind to the DHBV enhancer and interfere with viral transcription, resulting in decreased production of viral products and progeny virus genomes...
  52. Navrátilová A, Koblizkova A, Macas J. Survey of extrachromosomal circular DNA derived from plant satellite repeats. BMC Plant Biol. 2008;8:90 pubmed publisher
    ..been proposed that amplification and homogenization of satellite DNA could be facilitated by extrachromosomal circular DNA (eccDNA) molecules originated by recombination-based excision from satellite repeat arrays...
  53. Burnier Y, Dorier J, Stasiak A. DNA supercoiling inhibits DNA knotting. Nucleic Acids Res. 2008;36:4956-63 pubmed publisher
    ..DNA supercoiling, such as found in bacterial cells, creates a situation where intramolecular passages leading to knotting are opposed by the free-energy change connected to transitions from unknotted to knotted circular DNA molecules.