Biopolym. Cell. 2000; 16(4):301-311.
Genome and Its Regulation
Extrachromosomal DNA in eukaryotic cells
1Krysan K. V.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680

Abstract

Two forms of transgenes are known – Integrated into the host genome and extrachromosomal. Although the integrated transgenes are more common, the extrachromosomal ones are more interesting and perspective for the purposes of biotechnology and biomedicine. However, the mechanisms determining the fate of the extrachromosomal DNA molecule, have not been entirely studied so far. In this review we discuss these mechanisms and consider the extrachromosomal DNA of different origin.

References

[1] Schimke RT. Gene amplification in cultured animal cells. Cell. 1984;37(3):705-13.
[2] Maurer BJ, Lai E, Hamkalo BA, Hood L, Attardi G. Novel submicroscopic extrachromosomal elements containing amplified genes in human cells. Nature. 1987 Jun 4-10;327(6121):434-7.
[3] Looney JE, Hamlin JL. Isolation of the amplified dihydrofolate reductase domain from methotrexate-resistant Chinese hamster ovary cells. Mol Cell Biol. 1987;7(2):569-77.
[4] Grondin K, K?ndig C, Roy G, Ouellette M. Linear amplicons as precursors of amplified circles in methotrexate-resistant Leishmania tarentolae. Nucleic Acids Res. 1998;26(14):3372-8.
[5] Carroll SM, Gaudray P, De Rose ML, Emery JF, Meinkoth JL, Nakkim E, Subler M, Von Hoff DD, Wahl GM. Characterization of an episome produced in hamster cells that amplify a transfected CAD gene at high frequency: functional evidence for a mammalian replication origin. Mol Cell Biol. 1987;7(5):1740-50.
[6] Nonet GH, Carroll SM, DeRose ML, Wahl GM. Molecular dissection of an extrachromosomal amplicon reveals a circular structure consisting of an imperfect inverted duplication. Genomics. 1993;15(3):543-58.
[7] Hamlin JL, Milbrandt JD, Heintz NH, Azizkhan JC. DNA sequence amplification in mammalian cells. Int Rev Cytol. 1984;90:31-82.
[8] Yamada K, Kato H, Kanda N, Fujii-Kuriyama Y, Utakoji T, Itoh R. Sequence homology of Chinese hamster metallothionein genes I and II to those of the mouse and rat, and their amplification in Cd-resistant cells. Biochim Biophys Acta. 1994;1219(3):581-91.
[9] Giulotto E, Knights C, Stark GR. Hamster cells with increased rates of DNA amplification, a new phenotype. Cell. 1987;48(5):837-45.
[10] Emanuel JR, Garetz S, Schneider J, Ash JF, Benz EJ Jr, Levenson R. Amplification of DNA sequences coding for the Na,K-ATPase alpha-subunit in ouabain-resistant C+ cells. Mol Cell Biol. 1986;6(7):2476-81.
[11] Kanalas JJ, Suttle DP. Amplification of the UMP synthase gene and enzyme overproduction in pyrazofurin-resistant rat hepatoma cells. Molecular cloning of a cDNA for UMP synthase. J Biol Chem. 1984;259(3):1848-53.
[12] Ma C, Leu TH, Hamlin JL. Multiple origins of replication in the dihydrofolate reductase amplicons of a methotrexate-resistant chinese hamster cell line. Mol Cell Biol. 1990;10(4):1338-46.
[13] Dijkwel PA, Vaughn JP, Hamlin JL. Replication initiation sites are distributed widely in the amplified CHO dihydrofolate reductase domain. Nucleic Acids Res. 1994;22(23):4989-96.
[14] DePamphilis ML. Origins of DNA replication in metazoan chromosomes. J Biol Chem. 1993;268(1):1-4.
[15] Caddle MS, Calos MP. Analysis of the autonomous replication behavior in human cells of the dihydrofolate reductase putative chromosomal origin of replication. Nucleic Acids Res. 1992;20(22):5971-8.
[16] Kelly RE, DeRose ML, Draper BW, Wahl GM. Identification of an origin of bidirectional DNA replication in the ubiquitously expressed mammalian CAD gene. Mol Cell Biol. 1995;15(8):4136-48.
[17] Brison O. Gene amplification and tumor progression. Biochim Biophys Acta. 1993;1155(1):25-41.
[18] Brodeur GM, Seeger RC, Schwab M, Varmus HE, Bishop JM. Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage. Science. 1984;224(4653):1121-4.
[19] Kinzler KW, Zehnbauer BA, Brodeur GM, Seeger RC, Trent JM, Meltzer PS, Vogelstein B. Amplification units containing human N-myc and c-myc genes. Proc Natl Acad Sci U S A. 1986;83(4):1031-5.
[20] Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235(4785):177-82.
[21] Trent J, Meltzer P, Rosenblum M, Harsh G, Kinzler K, Mashal R, Feinberg A, Vogelstein B. Evidence for rearrangement, amplification, and expression of c-myc in a human glioblastoma. Proc Natl Acad Sci U S A. 1986;83(2):470-3.
[22] Schneider SS, Hiemstra JL, Zehnbauer BA, Taillon-Miller P, Le Paslier DL, Vogelstein B, Brodeur GM. Isolation and structural analysis of a 1.2-megabase N-myc amplicon from a human neuroblastoma. Mol Cell Biol. 1992;12(12):5563-70.
[23] Von Hoff DD, Needham-VanDevanter DR, Yucel J, Windle BE, Wahl GM. Amplified human MYC oncogenes localized to replicating submicroscopic circular DNA molecules. Proc Natl Acad Sci U S A. 1988;85(13):4804-8.
[24] McWhinney C, Leffak M. Autonomous replication of a DNA fragment containing the chromosomal replication origin of the human c-myc gene. Nucleic Acids Res. 1990;18(5):1233-42.
[25] Sudo K, Ogata M, Sato Y, Iguchi-Ariga SM, Ariga H. Cloned origin of DNA replication in c-myc gene can function and be transmitted in transgenic mice in an episomal state. Nucleic Acids Res. 1990;18(18):5425-32.
[26] Eckhardt SG, Dai A, Davidson KK, Forseth BJ, Wahl GM, Von Hoff DD. Induction of differentiation in HL60 cells by the reduction of extrachromosomally amplified c-myc. Proc Natl Acad Sci U S A. 1994;91(14):6674-8.
[27] Filmus J, Trent JM, Pollak MN, Buick RN. Epidermal growth factor receptor gene-amplified MDA-468 breast cancer cell line and its nonamplified variants. Mol Cell Biol. 1987;7(1):251-7.
[28] Sen S, Zhou H, White RA. A putative serine/threonine kinase encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene. 1997;14(18):2195-200.
[29] Lisitsyn NA, Lisitsina NM, Dalbagni G, Barker P, Sanchez CA, Gnarra J, Linehan WM, Reid BJ, Wigler MH. Comparative genomic analysis of tumors: detection of DNA losses and amplification. Proc Natl Acad Sci U S A. 1995;92(1):151-5.
[30] Tsuruta H, Sakamoto H, Onda M, Terada M. Amplification and overexpression of EXP1 and EXP2/Cyclin D1 genes in human esophageal carcinomas. Biochem Biophys Res Commun. 1993;196(3):1529-36.
[31] Buckley MF, Sweeney KJ, Hamilton JA, Sini RL, Manning DL, Nicholson RI, deFazio A, Watts CK, Musgrove EA, Sutherland RL. Expression and amplification of cyclin genes in human breast cancer. Oncogene. 1993;8(8):2127-33.
[32] Leach FS, Elledge SJ, Sherr CJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B. Amplification of cyclin genes in colorectal carcinomas. Cancer Res. 1993;53(9):1986-9.
[33] Khatib ZA, Matsushime H, Valentine M, Shapiro DN, Sherr CJ, Look AT. Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas. Cancer Res. 1993;53(22):5535-41.
[34] Visakorpi T, Hyytinen E, Koivisto P, Tanner M, Kein?nen R, Palmberg C, Palotie A, Tammela T, Isola J, Kallioniemi OP. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet. 1995;9(4):401-6.
[35] Almeida A, Zhu XX, Vogt N, Tyagi R, Muleris M, Dutrillaux AM, Dutrillaux B, Ross D, Malfoy B, Hanash S. GAC1, a new member of the leucine-rich repeat superfamily on chromosome band 1q32.1, is amplified and overexpressed in malignant gliomas. Oncogene. 1998;16(23):2997-3002.
[36] Kokkola A, Monni O, Puolakkainen P, Larramendy ML, Victorzon M, Nordling S, Haapiainen R, Kivilaakso E, Knuutila S. 17q12-21 amplicon, a novel recurrent genetic change in intestinal type of gastric carcinoma: a comparative genomic hybridization study. Genes Chromosomes Cancer. 1997;20(1):38-43.
[37] Carroll SM, DeRose ML, Gaudray P, Moore CM, Needham-Vandevanter DR, Von Hoff DD, Wahl GM. Double minute chromosomes can be produced from precursors derived from a chromosomal deletion. Mol Cell Biol. 1988;8(4):1525-33.
[38] Balaban-Malenbaum G, Gilbert F. The proposed origin of double minutes from Homogeneously Staining Region (HSR)-marker chromosomes in human neuroblastoma hybrid cell lines. Cancer Genet Cytogenet. 1980;2(4):339-48.
[39] George DL, Powers VE. Amplified DNA sequences in Y1 mouse adrenal tumor cells: association with double minutes and localization to a homogeneously staining chromosomal region. Proc Natl Acad Sci U S A. 1982;79(5):1597-601.
[40] Hahn PJ. Molecular biology of double-minute chromosomes. Bioessays. 1993;15(7):477-84.
[41] Wright JA, Smith HS, Watt FM, Hancock MC, Hudson DL, Stark GR. DNA amplification is rare in normal human cells. Proc Natl Acad Sci U S A. 1990;87(5):1791-5.
[42] Tlsty TD. Normal diploid human and rodent cells lack a detectable frequency of gene amplification. Proc Natl Acad Sci U S A. 1990;87(8):3132-6.
[43] Okazaki K, Davis DD, Sakano H. T cell receptor beta gene sequences in the circular DNA of thymocyte nuclei: direct evidence for intramolecular DNA deletion in V-D-J joining. Cell. 1987;49(4):477-85.
[44] Spradling AC, Mahowald AP. Amplification of genes for chorion proteins during oogenesis in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1980;77(2):1096-100.
[45] Calvi BR, Lilly MA, Spradling AC. Cell cycle control of chorion gene amplification. Genes Dev. 1998;12(5):734-44.
[46] Wu Z, Gall JG. "Micronucleoli" in the Xenopus germinal vesicle. Chromosoma. 1997;105(7-8):438-43.
[47] Kloc M, Matuszewski B, Nurkowska J. Ribosomal gene amplification in the oocytes of Creophilus maxillosus (Staphylinidae, Coleoptera-polyphaga)--an insect with telotrophic ovaries. Folia Histochem Cytobiol. 1995;33(4):267-76.
[48] Kubrakiewicz J, Bili?ski SM. Extrachromosomal amplification of rDNA in oocytes of Hemerobius spp. (Insecta, Neuroptera). Chromosoma. 1995;103(9):606-12.
[49] Suzuki H, Ingersoll J, Stern DB, Kindle KL. Generation and maintenance of tandemly repeated extrachromosomal plasmid DNA in Chlamydomonas chloroplasts. Plant J. 1997;11(4):635-48.
[50] Sinclair DA, Guarente L. Extrachromosomal rDNA circles--a cause of aging in yeast. Cell. 1997;91(7):1033-42.
[51] Wegner M, Zastrow G, Klavinius A, Schwender S, M?ller F, Luksza H, Hoppe J, Wienberg J, Grummt F. Cis-acting sequences from mouse rDNA promote plasmid DNA amplification and persistence in mouse cells: implication of HMG-I in their function. Nucleic Acids Res. 1989;17(23):9909-32.
[52] Wahl GM, Vitto L, Rubnitz J. Co-amplification of rRNA genes with CAD genes in N-(phosphonacetyl)-L-aspartate-resistant Syrian hamster cells. Mol Cell Biol. 1983;3(11):2066-75.
[53] Tantravahi U, Guntaka RV, Erlanger BF, Miller OJ. Amplified ribosomal RNA genes in a rat hepatoma cell line are enriched in 5-methylcytosine. Proc Natl Acad Sci U S A. 1981;78(1):489-93.
[54] Romanchikov YuM. The hypothesis of extrachromosomal regulatory genes. Usp Sovrem Biol. 1991; 111:643-53.
[55] Boccaccio C, Apiou F, Deschatrette J, Aurias A, Meunier-Rotival M. Chromosomal localization and sequence analysis of a human episomal sequence with in vitro differentiating activity. Somat Cell Mol Genet. 1994;20(3):163-70.
[56] Ng KH, Maign? J, Deschatrette J. The inductive effect of a human DNA sequence (HALF1) on the differentiation of a variant rat hepatoma cell (C2) is restricted to episomal forms of the molecule. J Cell Sci. 1995;108 ( Pt 4):1703-13.
[57] Boccaccio C, Meunier-Rotival M, Deschatrette J. Analysis of the inductive effect of the genomic equivalent of HALF1 sequence in the reversion of rat dedifferentiated hepatoma cells. Exp Cell Res. 1994;213(1):113-20.
[58] Arakawa H, Shimizu T, Iwakura Y, Yamagishi H. Molecular characterization of extrachromosomal circular DNAs from differentiating embryonic stem cells. Cell Struct Funct. 1996;21(6):451-7.
[59] Iwasato T, Shimizu T, Kanari Y, Yamagishi H. Molecular characterization of extrachromosomal circular DNAs from an embryonal carcinoma cell line induced to differentiate into neuron-like cells in vitro. Cell Struct Funct. 1993;18(4):261-6.
[60] Levin M. Left-right asymmetry in vertebrate embryogenesis. Bioessays. 1997;19(4):287-96.
[61] Rush MG, Misra R. Extrachromosomal DNA in eucaryotes. Plasmid. 1985;14(3):177-91.
[62] Sal'nokov KV. Extrachromosomal DNA in mammalian cells. Tsitologiia. 1990;32(11):1061-71.
[63] DeLap RJ, Rush MG. Change in quantity and size distribution of small circular DNAs during development of chicken bursa. Proc Natl Acad Sci U S A. 1978;75(12):5855-9.
[64] Makino Y, Kanno R, Koseki H, Taniguchi M. Development of Valpha4+ NK T cells in the early stages of embryogenesis. Proc Natl Acad Sci U S A. 1996;93(13):6516-20.
[65] Buchowicz J. Nuclear extrachromosomal DNA of higher plants. Acta Biochim Pol. 1997;44(1):13-9.
[66] Stanfield SW, Helinski DR. Cloning and characterization of small circular DNA from Chinese hamster ovary cells. Mol Cell Biol. 1984;4(1):173-80.
[67] Kiyama R, Matsui H, Oishi M. A repetitive DNA family (Sau3A family) in human chromosomes: extrachromosomal DNA and DNA polymorphism. Proc Natl Acad Sci U S A. 1986;83(13):4665-9.
[68] Flores SC, Moore TK, Gaubatz JW. Dispersed repetitive sequences of the mouse genome are differentially represented in extrachromosomal circular DNAs in vivo. Plasmid. 1987;17(3):257-60.
[69] Flores SC, Sunnerhagen P, Moore TK, Gaubatz JW. Characterization of repetitive sequence families in mouse heart small polydisperse circular DNAs: age-related studies. Nucleic Acids Res. 1988;16(9):3889-906.
[70] Jones RS, Potter SS. L1 sequences in HeLa extrachromosomal circular DNA: evidence for circularization by homologous recombination. Proc Natl Acad Sci U S A. 1985;82(7):1989-93.
[71] Assum G, Fink T, Steinbeisser T, Fisel KJ. Analysis of human extrachromosomal DNA elements originating from different beta-satellite subfamilies. Hum Genet. 1993;91(5):489-95.
[72] Yang Z, Boffelli D, Boonmark N, Schwartz K, Lawn R. Apolipoprotein(a) gene enhancer resides within a LINE element. J Biol Chem. 1998;273(2):891-7.
[73] Naas TP, DeBerardinis RJ, Moran JV, Ostertag EM, Kingsmore SF, Seldin MF, Hayashizaki Y, Martin SL, Kazazian HH. An actively retrotransposing, novel subfamily of mouse L1 elements. EMBO J. 1998;17(2):590-7.
[74] Paulson KE, Deka N, Schmid CW, Misra R, Schindler CW, Rush MG, Kadyk L, Leinwand L. A transposon-like element in human DNA. Nature. 1985 Jul 25-31;316(6026):359-61.
[75] Fujimoto S, Tsuda T, Toda M, Yamagishi H. Transposon-like sequences in extrachromosomal circular DNA from mouse thymocytes. Proc Natl Acad Sci U S A. 1985;82(7):2072-6.
[76] Landry S, Zannis-Hadjopoulos M. Classes of autonomously replicating sequences are found among early-replicating monkey DNA. Biochim Biophys Acta. 1991;1088(2):234-44.
[77] Renault S, Degroote F, Picard G. Despite its high representation in extrachromosomal circular DNAs from Drosophila embryos, the dodecasatellite does not allow autonomous replication in cultured cells. Biol Cell. 1993;79(1):51-4.
[78] Sunnerhagen P, Sj?berg RM, Karlsson AL, Lundh L, Bjursell G. Molecular cloning and characterization of small polydisperse circular DNA from mouse 3T6 cells. Nucleic Acids Res. 1986;14(20):7823-38.
[79] Kusano T, Uehara H, Saito H, Segawa K, Oishi M. Multicopy plasmid with a structure related to the polyoma virus genome. Proc Natl Acad Sci U S A. 1987;84(7):1789-93.
[80] Nishimori K, Kohda T, Fujiwara J, Oishi M. Establishment of composite DNA derived from L factor as a plasmid in mouse embryonal carcinoma (F9) cells. Mol Cell Biol. 1988;8(5):2097-104.
[81] Hegger R, Abken H. The short DNA sequences in the cytoplasm of Ehrlich ascites tumor cells are tightly associated with proteins. Physiol Chem Phys Med NMR. 1995;27(4):321-8.
[82] Abken H, Hegger R, B?tzler C, Willecke K. Short DNA sequences from the cytoplasm of mouse tumor cells induce immortalization of human lymphocytes in vitro. Proc Natl Acad Sci U S A. 1993;90(14):6518-22.
[83] van Loon N, Miller D, Murnane JP. Formation of extrachromosomal circular DNA in HeLa cells by nonhomologous recombination. Nucleic Acids Res. 1994;22(13):2447-52.
[84] Calos MP. The potential of extrachromosomal replicating vectors for gene therapy. Trends Genet. 1996;12(11):463-6.
[85] Hyrien O, Debatisse M, Buttin G, de Saint Vincent BR. A hotspot for novel amplification joints in a mosaic of Alu-like repeats and palindromic A + T-rich DNA. EMBO J. 1987;6(8):2401-8.
[86] Meinkoth J, Killary AM, Fournier RE, Wahl GM. Unstable and stable CAD gene amplification: importance of flanking sequences and nuclear environment in gene amplification. Mol Cell Biol. 1987;7(4):1415-24.
[87] Von Hoff DD. New mechanisms of gene amplification in drug resistance (the episome model). Cancer Treat Res. 1991;57:1-11.
[88] Ford M, Fried M. Large inverted duplications are associated with gene amplification. Cell. 1986;45(3):425-30.
[89] Passananti C, Davies B, Ford M, Fried M. Structure of an inverted duplication formed as a first step in a gene amplification event: implications for a model of gene amplification. EMBO J. 1987;6(6):1697-703.
[90] Ma C, Martin S, Trask B, Hamlin JL. Sister chromatid fusion initiates amplification of the dihydrofolate reductase gene in Chinese hamster cells. Genes Dev. 1993;7(4):605-20.
[91] Georgiev PG, Korochkina SE, Georgieva SG, Gerasimova TI. Mitomycin C induces genomic rearrangements involving transposable elements in Drosophila melanogaster. Mol Gen Genet. 1990;220(2):229-33.
[92] Hellgren D. Mutagen-induced recombination in mammalian cells in vitro. Mutat Res. 1992;284(1):37-51.
[93] Lavi S. Carcinogen-mediated amplification of viral DNA sequences in simian virus 40-transformed Chinese hamster embryo cells. Proc Natl Acad Sci U S A. 1981;78(10):6144-8.
[94] Lipskaia LA, Zhitkovich AV, Vasiukhin VI, Tsvetkov AG, Sal'nikov KV. The participation of endonuclease in the formation of extrachromosomal DNA and the possible mechanisms of the occurrence of gene amplification. Tsitologiia. 1993;35(1):70-8.
[95] Simonsson T, Pecinka P, Kubista M. DNA tetraplex formation in the control region of c-myc. Nucleic Acids Res. 1998;26(5):1167-72.
[96] Alberti S, Nutini M, Herzenberg LA. DNA methylation prevents the amplification of TROP1, a tumor-associated cell surface antigen gene. Proc Natl Acad Sci U S A. 1994;91(13):5833-7.
[97] Gibbs M, Collick A, Kelly RG, Jeffreys AJ. A tetranucleotide repeat mouse minisatellite displaying substantial somatic instability during early preimplantation development. Genomics. 1993;17(1):121-8.
[98] Ohki R, Oishi M, Kiyama R. Preference of the recombination sites involved in the formation of extrachromosomal copies of the human alphoid Sau3A repeat family. Nucleic Acids Res. 1995;23(24):4971-7.
[99] Wiberg FC, Sunnerhagen P, Bjursell G. New, small circular DNA in transfected mammalian cells. Mol Cell Biol. 1986;6(2):653-62.
[100] Windle B, Draper BW, Yin YX, O'Gorman S, Wahl GM. A central role for chromosome breakage in gene amplification, deletion formation, and amplicon integration. Genes Dev. 1991;5(2):160-74.
[101] Sen S, Sen P, Mulac-Jericevic B, Zhou H, Pirrotta V, Stass SA. Microdissected double-minute DNA detects variable patterns of chromosomal localizations and multiple abundantly expressed transcripts in normal and leukemic cells. Genomics. 1994;19(3):542-51.
[102] George RE, Kenyon RM, McGuckin AG, Malcolm AJ, Pearson AD, Lunec J. Investigation of co-amplification of the candidate genes ornithine decarboxylase, ribonucleotide reductase, syndecan-1 and a DEAD box gene, DDX1, with N-myc in neuroblastoma. United Kingdom Children's Cancer Study Group. Oncogene. 1996;12(7):1583-7.
[103] Kim JO, Nau MM, Allikian KA, M?kel? TP, Alitalo K, Johnson BE, Kelley MJ. Co-amplification of a novel cyclophilin-like gene (PPIE) with L-myc in small cell lung cancer cell lines. Oncogene. 1998;17(8):1019-26.
[104] Wang XY, Smith DI, Frederick L, James CD. Analysis of EGF receptor amplicons reveals amplification of multiple expressed sequences. Oncogene. 1998;16(2):191-5.
[105] Coquelle A, Pipiras E, Toledo F, Buttin G, Debatisse M. Expression of fragile sites triggers intrachromosomal mammalian gene amplification and sets boundaries to early amplicons. Cell. 1997;89(2):215-25.
[106] Schlegel J, Stumm G, Scherthan H, Bocker T, Zirngibl H, R?schoff J, Hofst?dter F. Comparative genomic in situ hybridization of colon carcinomas with replication error. Cancer Res. 1995;55(24):6002-5.
[107] Caddle MS, Dailey L, Heintz NH. RIP60, a mammalian origin-binding protein, enhances DNA bending near the dihydrofolate reductase origin of replication. Mol Cell Biol. 1990;10(12):6236-43.
[108] Rice GC, Hoy C, Schimke RT. Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1986;83(16):5978-82.
[109] Albertoni M, Daub DM, Arden KC, Viars CS, Powell C, Van Meir EG. Genetic instability leads to loss of both p53 alleles in a human glioblastoma. Oncogene. 1998;16(3):321-6.
[110] Queimado L, Reis A, Fonseca I, Martins C, Lovett M, Soares J, Parreira L. A refined localization of two deleted regions in chromosome 6q associated with salivary gland carcinomas. Oncogene. 1998;16(1):83-8.
[111] Livingstone LR, White A, Sprouse J, Livanos E, Jacks T, Tlsty TD. Altered cell cycle arrest and gene amplification potential accompany loss of wild-type p53. Cell. 1992;70(6):923-35.
[112] Paulson TG, Almasan A, Brody LL, Wahl GM. Gene amplification in a p53-deficient cell line requires cell cycle progression under conditions that generate DNA breakage. Mol Cell Biol. 1998;18(5):3089-100.
[113] Shimizu N, Itoh N, Utiyama H, Wahl GM. Selective entrapment of extrachromosomally amplified DNA by nuclear budding and micronucleation during S phase. J Cell Biol. 1998;140(6):1307-20.
[114] Yin Y, Tainsky MA, Bischoff FZ, Strong LC, Wahl GM. Wild-type p53 restores cell cycle control and inhibits gene amplification in cells with mutant p53 alleles. Cell. 1992;70(6):937-48.
[115] Ishizaka Y, Chernov MV, Burns CM, Stark GR. p53-dependent growth arrest of REF52 cells containing newly amplified DNA. Proc Natl Acad Sci U S A. 1995;92(8):3224-8.
[116] Chernova OB, Chernov MV, Ishizaka Y, Agarwal ML, Stark GR. MYC abrogates p53-mediated cell cycle arrest in N-(phosphonacetyl)-L-aspartate-treated cells, permitting CAD gene amplification. Mol Cell Biol. 1998;18(1):536-45.
[117] Maiti AK, Sinha P. The mcm2 mutation of yeast affects replication, rather than segregation or amplification of the two micron plasmid. J Mol Biol. 1992;224(3):545-58.
[118] Chong JP, Th?mmes P, Blow JJ. The role of MCM/P1 proteins in the licensing of DNA replication. Trends Biochem Sci. 1996;21(3):102-6.
[119] Yan H, Merchant AM, Tye BK. Cell cycle-regulated nuclear localization of MCM2 and MCM3, which are required for the initiation of DNA synthesis at chromosomal replication origins in yeast. Genes Dev. 1993;7(11):2149-60.
[120] Treisman JE, Follette PJ, O'Farrell PH, Rubin GM. Cell proliferation and DNA replication defects in a Drosophila MCM2 mutant. Genes Dev. 1995;9(14):1709-15.
[121] Hammond DW, Hancock BW, Goyns MH. Identification of a subclass of double minute chromosomes containing centromere-associated DNA. Genes Chromosomes Cancer. 1994;10(2):139-42.
[122] Choo KH. Turning on the centromere. Nat Genet. 1998;18(1):3-4.
[123] Williams BC, Murphy TD, Goldberg ML, Karpen GH. Neocentromere activity of structurally acentric mini-chromosomes in Drosophila. Nat Genet. 1998;18(1):30-7.
[124] Renault S, Degroote F, Picard G. Identification of short tandemly repeated sequences in extrachromosomal circular DNAs from Drosophila melanogaster embryos. Genome. 1993;36(2):244-54.
[125] Lehman CW, Botchan MR. Segregation of viral plasmids depends on tethering to chromosomes and is regulated by phosphorylation. Proc Natl Acad Sci U S A. 1998;95(8):4338-43.
[126] Murakami Y, Huberman JA, Hurwitz J. Identification, purification, and molecular cloning of autonomously replicating sequence-binding protein 1 from fission yeast Schizosaccharomyces pombe. Proc Natl Acad Sci U S A. 1996;93(1):502-7.