Biology:Extrachromosomal Circular DNA
Extrachromosomal circular DNA (eccDNA) is circular DNA found in the nuclei of plant and animal cells, including human cells, in addition to chromosomal DNA. eccDNA can be from 200 up to 5 million base pairs in length.[1][2] eccDNA has been found in the nuclei of human cancer cells and shown to carry many copies of driver oncogenes which are transcribed in tumour cells.[3] Based on this evidence it is thought that eccDNA contributes to cancer growth.
Subtypes
MicroDNA is the most abundant subtype of Extrachromosomal Circular DNA (eccDNA) in humans.[2][4] They are 200-400 base pairs in length are enriched in genic sequences and CpG islands. MicroDNA have been detected the bloodstream of cancer patients and may become a biomarker for detection of cancer.[5] Further, microDNA formation has been tied to chemotherapeutic treatment.[6][7]
Double minutes are small fragments of extrachromosomal DNA, which have been observed in a large number of human tumors including breast, lung, ovary, colon, and most notably, neuroblastoma. They are a manifestation of gene amplification during the development of tumors, which give the cells selective advantages for growth and survival. They frequently harbor amplified oncogenes and genes involved in drug resistance. Double minutes, like actual chromosomes, are composed of chromatin and replicate in the nucleus of the cell during cell division. Unlike typical chromosomes, they are composed of circular fragments of DNA, up to only a few million base pairs in size and contain no centromere or telomere.
See also
- Extrachromosomal DNA
- Extrachromosomal rDNA circle
- Selfish genetic elements
- microDNA
- Double minute
References
- ↑ "Circular DNA throws biologists for a loop". Science 356 (6342): 996. June 2017. doi:10.1126/science.356.6342.996. PMID 28596318.
- ↑ 2.0 2.1 "Production of Extrachromosomal MicroDNAs Is Linked to Mismatch Repair Pathways and Transcriptional Activity". Cell Reports 11 (11): 1749–59. June 2015. doi:10.1016/j.celrep.2015.05.020. PMID 26051933.
- ↑ "Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity". Nature 543 (7643): 122–125. March 2017. doi:10.1038/nature21356. PMID 28178237.
- ↑ "Extrachromosomal microDNAs and chromosomal microdeletions in normal tissues". Science 336 (6077): 82–6. April 2012. doi:10.1126/science.1213307. PMID 22403181.
- ↑ "Normal and Cancerous Tissues Release Extrachromosomal Circular DNA (eccDNA) into the Circulation". Molecular Cancer Research 15 (9): 1197–1205. September 2017. doi:10.1158/1541-7786.MCR-17-0095. PMID 28550083.
- ↑ "Characterization of the microDNA through the response to chemotherapeutics in lymphoblastoid cell lines". PLOS One 12 (9): e0184365. 2017. doi:10.1371/journal.pone.0184365. PMID 28877255.
- ↑ "Discoveries of Extrachromosomal Circles of DNA in Normal and Tumor Cells". Trends in Genetics 34 (4): 270–278. April 2018. doi:10.1016/j.tig.2017.12.010. PMID 29329720.
- Baskin, F; Rosenberg, RN; Dev, V (June 1981). "Correlation of double-minute chromosomes with unstable multidrug cross-resistance in uptake mutants of neuroblastoma cells". Proc Natl Acad Sci USA 78 (6): 3654–3658. doi:10.1073/pnas.78.6.3654. PMID 6943568. Free full-text.
- Barker PE (February 1982). "Double minutes in human tumor cells". Cancer genetics and cytogenetics 5 (1): 81–94. doi:10.1016/0165-4608(82)90043-7. PMID 6175392. http://linkinghub.elsevier.com/retrieve/pii/0165-4608(82)90043-7.
- Masters, J; Keeley, B; Gay, H; Attardi, G (1982). "Variable content of double minute chromosomes is not correlated with degree of phenotype instability in methotrexate-resistant human cell lines". Mol Cell Biol 2 (5): 498–507. PMID 7110138. Free full-text.
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