Summary
Cell cultures were derived from angiofibromas of three patients with tuberous sclerosis (TSC), from the unaffected skin of these patients, and from the skin of five healthy donors. The length distributions of the small polydisperse circular DNA (spcDNA) fraction of these cell cultures were then analyzed. Nearly half the spcDNA molecules from the angiofibroma cultures were longer than 0.4 μm, whereas only about 7% exceeded this threshold in the spcDNA preparations from the skin fibroblast cultures. The percentage of the larger size class of spcDNA showed an increase at higher numbers of in vitro passages in all three types of cultures, but this effect was much more conspicuous in the angiofibroma-derived cultures than in those from the skin fibroblasts. An age-dependent increase in the overall amount of spcDNA was only seen in the angiofibroma-derived cultures. Our earlier finding of elevated amounts of spcDNA in angiofibroma cultures was confirmed in cultures from an additional TSC patient.
Similar content being viewed by others
References
Abken H, Bützler C, Willecke K (1988) Immortalization of human lymphocytes by transfection with DNA from mouse L929 cytoplasts. Proc Natl Acad Sci USA 85:468–472
Assum G, Böckle B, Fink T, Dmochewitz U, Krone W (1989) Restriction analysis of chromosomal sequences homologous to single-copy fragments cloned from small polydisperse circular DNA (spcDNA). Hum Genet 82:249–254
Bertelsen AH, Humayun MZ, Karfopoulos SG, Rush MG (1982) Molecular characterization of small polydisperse circular deoxyribonucleic acid from an African green monkey cell line. Biochemistry 21:2076–2085
Cairns J (1981) The origin of human cancers. Nature 289:353–357
Calabretta B, Robberson DL, Barrera-Saldaña HA, Lambron TP, Saudners GF (1982) Genome instability in a region of human DNA enriched in Alu repeat sequences. Nature 296:219–225
Dietrich CU, Krone W, Hochsattel R (1990) Cytogenetic studies in tuberous sclerosis. Cancer Genet Cytogenet 45:161–177
Engels WR (1980) Hybrid dysgenesis inDrosophila and the stochastic loss hypothesis. Cold Spring Harb Symp Quant Biol 45 [P2]:561–565
Engels WR (1983) The P-family of transposable elements inDrosophila (Review) Annu Rev Genet 17:313–344
Fanning TG, Singer MF (1987) Line-1: a mammalian transposable element. Biochim Biophys Acta 910:203–212
Fujimoto S, Yamagishi H (1987) Isolation of an excision product of T-cell receptor α-chain gene rearrangements. Nature 327:242–243
Fujimoto S, Tsuda T, Toda M, Yamagishi H (1985) Transposonlike sequences in extrachromosomal circular DNA from mouse thymocytes. Proc Natl Acad Sci USA 82:2072–2076
Gomez MR (1988) Criteria for diagnosis. Tuberous sclerosis, 2nd edn. Raven Press New York, pp 9–19
Hirt B (1967) Selective extraction of polyoma DNA from infected mouse cell cultures. J Mol Biol 26:365–369
Hollis M, Hindley J (1986) Human Sau3A repeated DNA is enriched in small polydisperse circular DNA from normal lymphocytes. Gene 46:153–160
Jones SJ, Potter SS (1985a) L1 sequence in HeLa extrachromosomal circular DNA: evidence for circularization by homologous recombination. Proc Natl Acad Sci USA 82:1989–1993
Jones SJ, Potter SS (1985b) Characterization of cloned human alphoid satellite with an unusual monomeric construction: evidence for enrichment in HeLa small polydisperse circular DNA. Nucleic Acids Res 13:1027–1042
Kiyama R, Matsui H, Okumura K, Oishi M (1987) A group of repetitive human DNA families that is characterized by extrachromosomal oligomers and restriction-fragment length polymorphism. J Mol Biol 913:591–597
Kleinschmidt AK, Zahn RK (1959) Über Desoxyribonucleinsäure-Molekeln in Protein-Mischfilmen. Z Naturforsch 14b:770–779
Krolewski JJ, Rush MG (1984) Some extrachromosomal circular DNAs containing the Alu family of dispersed repetitive sequences may be reverse transcripts. J Mol Biol 174:31–34
Krolewski JJ, Bertelsen AH, Humayun MZ, Rush MG (1982) Members of the Alu family of interspersed, repeptitive DNA sequences are in the small circular DNA population of monkey cells grown in culture. J Mol Biol 154:399–415
Krolewski JJ, Schindler CW, Rush MG (1984) Structure of extrachromosomal circular DNAs containing both the Alu family of dispersed repetitive sequences and other regions of chromosomal DNA. J Mol Biol 174:41–54
Kunisada T, Yamagishi H (1983) Rapid microscale procedure for visualizing intracellular plasmid DNA by electron microscopy. Plasmid 9:8–16
Kunisada T, Yamagishi H (1984) Sequence repetition and genomic distribution of small polydisperse circular DNA purified from HeLa cells. Gene 31:213–223
Kunisada T, Yamagishi H, Ogita ZI, Kirakawa T, Mitsui Y (1985) Appearance of extrachromosomal circular DNAs during in vivo and in vitro ageing of mammalian cells. Mech Ageing Dev 29:89–99
McClintock B (1950) The origin and behavior of mutable loci in maize. Proc Natl Acad Sci USA 36:344–355
Misra R, Shih A, Rush M (1987) Cloned extrachromosomal circular DNA copies of the human transposable element THE-1 are related predominantly to a single type of family member. J Mol Biol 196:233–243
Neidlinger C, Assum G, Krone W, Dietrich C, Hochsattel R, Klotz G (1988) Increased amounts of small polydisperse circular DNA (spcDNA) in angiofibroma-derived cell cultures from patients with tuberous sclerosis (TS). Hum Genet 79:286–288
Nevers P, Saedler H (1977) Transposable genetic elements as agents of gene instability and chromosomal rearrangements. Nature 268:109–115
Paulson KE, Deka N, Schmid CW, Misra R, Schindler CW, Rush MG, Kadyk L, Leinwand L (1985) A transposon-like element in human DNA. Nature 316:359–361
Riabowol KT, Shmookler Reis FJ, Goldstein S (1985) Interspersed repetitive and tandemly repetitive sequences are differentially represented in extrachromosomal covalently closed circular DNA of human diploid fibroblasts. Nucleic Acids Res 13:5563–5584
Rowley JD (1978) Are consistent chromosome abnormalities in human malignancy related to transposable elements? (abstract). Heredity 42:275
Sager R (1979) Transposable elements and chromosomal rearangement in cancer — a possible link. Nature 282:447–448
Scappaticci S, Cerimele D, Tondi M, Vivarelli R, Fois A, Fraccaro M (1988) Chromosome abnormalities in tuberous sclerosis. Hum Genet 79:151–156
Schindler CW, Rush MG (1985a) The KpnI family of long interspersed nucleotide sequences is present on discrete sizes of circular DNA in monkey (BSC-1) cells. J Mol Biol 181:161–173
Schindler CW, Rush MG (1985b) Discrete size classes of monkey extrachromosomal circular DNA containing the L1 family of long interspersed nucleotide sequences are produced by a general non-sequence-specific mechanism. Nucleic Acids Res 13:8247–8258
Toda M, Fujimoto S, Iwasato T, Takeshita S, Tezuka K, Ohbayashi T, Yamagishi H (1988) Structure of extrachromosomal circular DNAs excised from T-cell antigen receptor alpha and delta-chain loci. J Mol Biol 202:219–231
Toda M, Hirama T, Takeshita S, Yamagishi H (1989) Excision products of immunoglobulin gene rearrangements. Immunol Lett 21:311–316
Vollenweider HJ, Sogo JM, Koller TH (1975) A routine method for protein-free spreading of double- and single-stranded nucleic acid molecules. Proc Natl Acad Sci USA 72:83–87
Yamagishi H (1986) Role of mammalian circular DNA in cellular differentiation. Bioessays 4:218–221
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Motejlek, K., Assum, G., Krone, W. et al. The size of small polydisperse circular DNA (spcDNA) in angiofibroma-derived cell cultures from patients with tuberous sclerosis (TSC) differs from that in fibroblasts. Hum Genet 87, 6–10 (1991). https://doi.org/10.1007/BF01213083
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01213083