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Instabilities of Triplet Repeats: Factors and Mechanisms

  • Chapter
Trinucleotide Diseases and Instability

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 21))

Abstract

Repetitive DNA sequences are dispersed throughout natural genomes, both within and outside of known coding sequences (Charlesworth et al. 1994; Tautz and Schlotterer 1994). The varied distribution of particular repetitive sequences between different species suggests that they fulfill specific cellular requirements, but direct evidence for what these may be is lacking. However, any cellular functions are likely to be restricted to eukaryotes since long repeating sequences are absent from prokaryotic genomes.

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References

  • Aaltonen LA, Peltomaki P, Leach FS, Sistonen P, Pylkkanen L, Mecklin JP, Jarvinen H, Powell SM, Jen J, Hamilton SR, Petersen GM, Kinzler KW, Vogelstein B, de la Chapelle A (1993) Clues to the pathogenesis of familial colorectal cancer. Science 260:812–816

    Article  PubMed  CAS  Google Scholar 

  • Alfano C, McMacken R (1988) The role of template superhelicity in the initiation of bacteriophage λ DNA replication. Nucleic Acids Res 16:9611–9630

    Article  PubMed  CAS  Google Scholar 

  • Armour JA, Jeffreys AJ (1992) Biology and applications of human minisatellite loci. Curr Opin Genet Dev 2:850–856

    Article  PubMed  CAS  Google Scholar 

  • Ashley CT, Warren ST (1995) Trinucleotide repeat expansion and human disease. Annu Rev Genet 29:703–728

    Article  PubMed  CAS  Google Scholar 

  • Ashley CT, Sutcliffe JS, Kunst CB, Leiner HA, Eichler EE, Nelson DL, Warren ST (1993) Human and murine FMR-1: alternative splicing and translational initiation downstream of the CGG-repeat. Nat Genet 4:244–251

    Article  PubMed  CAS  Google Scholar 

  • Bacolla A, Gellibolian R, Shimizu M, Amirhaeri S, Kang S, Ohshima K, Larson JE, Harvey SC, Stollar BD, Wells RD (1997) Flexible DNA: genetically unstable CGG and CTG from human hereditary neuromuscular disease genes. J Biol Chem 272:16783–16792

    Article  PubMed  CAS  Google Scholar 

  • Baker SM, Bronner CE, Zhang L, Plug AW, Robatzek M, Warren G, Elliott EA, Yu J, Ashley T, Arnheim N, Flavell RA, Liskay RM (1995) Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82:309–319

    Article  PubMed  CAS  Google Scholar 

  • Bednar J, Furrer P, Katrich V, Stasiak AZ, Dubochet J, Stasiak A. (1995) Determination of DNA persistence length by cryo-electron microscopy. Separation of the static and dynamic contributions to the apparent persistence length of DNA. J Mol Biol 254:579–594

    Article  PubMed  CAS  Google Scholar 

  • Bingham PM, Scott MO, Wang S, McPhaul MJ, Wilson EM, Garbern JY, Merry DE, Fischbeck KH (1995) Stability of an expanded trinucleotide repeat in the androgen receptor gene in transgenic mice. Nat Genet 9:191–196

    Article  PubMed  CAS  Google Scholar 

  • Bowater RP, Rosche WA, Jaworski A, Sinden RR, Wells RD (1996) Relationship between Escherichia coli growth and deletions of CTG-CAG triplet repeats in plasmids. J Mol Biol 264:82–96

    Article  PubMed  CAS  Google Scholar 

  • Bowater RP, Jaworski A, Larson JE, Parniewski P, Wells RD (1997) Transcription increases the deletion frequency of CTG-CAG triplet repeat sequences from human neuromuscular disease genes in E. Coli. Nucleic Acids Res 25:2861–2868

    Article  PubMed  CAS  Google Scholar 

  • Burke JR, Enghild JJ, Martin ME, Jou YS, Myers RM, Roses AD, Vance JM, Strittmatter WJ (1996) Huntingtin and DRPLA proteins selectively interact with the enzyme GAPDH. Nat Med 2:347–350

    Article  PubMed  CAS  Google Scholar 

  • Burright EN, Clark HB, Servadio A, Matilla T, Feddersen RM, Yunis WS, Duvick LA, Zoghbi HY, Orr HT (1995) SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat. Cell 82:937–948

    Article  PubMed  CAS  Google Scholar 

  • Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, Monros E, Rodius F, Duclos F, Monticelli A, Zara F, Cañizares J, Koutnikova H, Bidichandani SI, Gellera C, Brice A, Trouillas P, de Michele G, Filla A, de Frutos R, Palau F, Patel PI, di Donato S, Mandel J-L, Cocozza S, Koenig M, Pandolfo M (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271:1423–1427

    Article  PubMed  CAS  Google Scholar 

  • Caskey CT, Pizzuti A, Fu YH, Fenwick RG Jr, Nelson DL (1992) Triplet repeat mutations in human disease. Science 256:784–789

    Article  PubMed  CAS  Google Scholar 

  • Charlesworth B, Sniegowski P, Stephan W (1994) The evolutionary dynamics of repetitive DNA in eucaryotes. Nature 371:215–220

    Article  PubMed  CAS  Google Scholar 

  • Chastain PD, Eichler EE, Kang S, Nelson DL, Levene SD, Sinden RR (1995) Anomalously rapid electrophoretic mobility of DNA containing triplet repeats associated with human disease genes. Biochemistry 34:16125–16131

    Article  PubMed  CAS  Google Scholar 

  • Chen X, Mariappan SVS, Catasti P, Ratliff R, Moyzis K, Laayoun A, Smith SS, Bradbury EM, Gupta G (1995) Hairpins are formed by the single DNA strands of the fragile X triplet repeats: structure and biological implications. Proc Natl Acad Sci USA 92:5199–5203

    Article  PubMed  CAS  Google Scholar 

  • Chung M-y, Ranum LPW, Duvick LA, Servadio A, Zoghbi HY, Orr HT (1993) Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type I. Nat Genet 5:254–258

    Article  PubMed  CAS  Google Scholar 

  • de la Chapelle A, Peltomaki P (1995) Genetics of hereditary colon cancer. Annu Rev Genet 29:329–348

    Article  PubMed  Google Scholar 

  • De Pamphilis ML (1993) Eukaryotic DNA replication: anatomy of an origin. Annu Rev Biochem 62:29–63

    Article  Google Scholar 

  • de Wind N, Dekker M, Berns A, Radman M, de Riele H (1995) Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82:321–330

    Article  PubMed  Google Scholar 

  • Diekmann S, Hillen W, Morgeneyer B, Wells RD, Pörscke D (1982) Orientation relaxation of DNA restriction fragments and the internal mobility of the double helix. Biophys Chem 15:263–270

    Article  PubMed  CAS  Google Scholar 

  • Dover G (1995) Slippery DNA runs on and on and on… Nat Genet 10:254

    Article  CAS  Google Scholar 

  • DuPraw EJ (1974) Quantitative constraints in the arrangement of human DNA. Cold Spring Harbor Symp Quant Biol 38:87–98

    Article  PubMed  CAS  Google Scholar 

  • Dutch-Belgian Fragile X Consortium (1994) Fmr1 knockout mice: a model to study Fragile X mental retardation. Cell 78:23–33

    Google Scholar 

  • Duyao M, Ambrose C, Myers R, Novelletto A, Persichetti F, Frontali M, Folstein S, Ross C, Franz M, Abbott M et al. (1993) Trinucleotide repeat length instability and age of onset in Hunting-ton’s disease. Nat Genet 4:387–392

    Article  PubMed  CAS  Google Scholar 

  • Duyao MP, Auerbach AB, Ryan A, Persichetti F, Barnes GT, McNeil SM, Ge P, Vonsattel J-P, Gusella JF, Joyner AL, MacDonald ME (1995) Inactivation of the mouse Huntington’s disease gene homologue Hdh. Science 269:407–410

    Article  PubMed  CAS  Google Scholar 

  • Eichler EE, Holden JJ, Popovich BW, Reiss AL, Snow K, Thibodeau SN, Richards CS, Ward PA, Nelson DL (1994) Length of uninterrupted CGG repeats determines instability in the FMR1 gene. Nat Genet 8:88–94

    Article  PubMed  CAS  Google Scholar 

  • Eichler EE, Hammond HA, Macpherson JN, Ward PA, Nelson DL (1995) Population survey of the human FMR1 CGG repeat substructure suggests biased polarity of the loss of AGG interruption. Hum Mol Genet 4:2199–2208

    Article  PubMed  CAS  Google Scholar 

  • Eshelmann JR, Markowitz SD (1996) Mismatch repair defects in human carcinogenesis. Hum Mol Genet 5:1489–1494

    Google Scholar 

  • Fishel R, Kolodner RD (1995) Identification of mismatch repair genes and their role in the development of cancer. Curr Opin Genet Dev 5:382–395

    Article  PubMed  CAS  Google Scholar 

  • Fishel R, Lescoe MK, Rao MRS, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R (1993) The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:1027–1038

    Article  PubMed  CAS  Google Scholar 

  • Freudenreich CH, Stavenhagen JB, Zakian VA (1997) Stability of a CTG/CAG trinucleotide repeat in yeast is dependent on its orientation in the genome. Mol Cell Biol 17:2090–2098

    PubMed  CAS  Google Scholar 

  • Freund AM, Bichara M, Fuchs RP (1989) Z-DNA-forming sequences are spontaneous deletion hot spots. Proc Natl Acad Sci USA 86:7465–7469

    Article  PubMed  CAS  Google Scholar 

  • Fry M, Loeb LA (1994) The fragile X syndrome d(CGG)n nucleotide repeats form a stable tetrahelical structure. Proc Natl Acad Sci USA 91:4950–4954

    Article  PubMed  CAS  Google Scholar 

  • Fu Y-H, Kuhl DPA, Pizzuti A, Pieretti M, Sutcliffe JS, Richards S, Verkerk AJMH, Holden JJA, Fenwick RG Jr, Warren ST, Oostra BA, Nelson DL, Caskey CT (1991) Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. Cell 67:1047–1058

    Article  PubMed  CAS  Google Scholar 

  • Fu Y-H, Pizzuti A, Fenwick RG Jr, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong P, Wieringa B, Korneluk R, Perryman MB, Epstein HF, Caskey CT (1992) An unstable triplet repeat in a gene related to myotonic muscular dystrophy. Science 255:1256–1258

    Article  PubMed  CAS  Google Scholar 

  • Gacy AM, Goellner G, Juranic N, Macura S, McMurray CT (1995) Trinucleotide repeats that expand in human disease form hairpin structures in vitro. Cell 81:533–540

    Article  PubMed  CAS  Google Scholar 

  • Gastier JM, Pulido JC, Sunden S, Brody T, Buetow KH, Murray JC, Weber JL, Hudson TJ, Sheffield VC, Duyk GM (1995) Survey of trinucleotide repeats in the human genome: assessment of their utility as genetic markers. Hum Mol Genet 4:1829–1836

    Article  PubMed  CAS  Google Scholar 

  • Gellibolian R, Bacolla A, Wells RD (1997) Triplet repeat instability and DNA topology: A expansion model based on statistical mechanics. J Biol Chem 27:16793–16797

    Article  Google Scholar 

  • Goldberg YP, Kalchman MA, Metzler M, Nasir J, Zeisler J, Graham R, Koide HB, O’Kusky J, Sharp AH, Ross CA, Jirik F, Hayden MR (1996) Absence of disease phenotype and intergenerational stability of the CAG repeat in transgenic mice expressing the human Huntington disease transcript. Hum Mol Genet 5:177–185

    Article  PubMed  CAS  Google Scholar 

  • Hagerman PJ (1988) Flexibility of DNA. Annu Rev Biophys Biophys Chem 17:265–286

    Article  PubMed  CAS  Google Scholar 

  • Hagerman PJ, Ramadevi VA (1990) Application of the method of phage T4 DNA ligase-catalyzed ring-closure to the study of DNA structure. I. Computational analysis. J Mol Biol 212:351–362

    Article  PubMed  CAS  Google Scholar 

  • Hancock JM (1996) Simple sequences and the expanding genome. Bioessays 18:421–425

    Article  PubMed  CAS  Google Scholar 

  • Harris S, Moncrieff C, Johnson K (1996) Myotonic dystrophy: will the real gene please step forward! Hum Mol Genet 5:1417–1423

    PubMed  CAS  Google Scholar 

  • Hodges-Garcia Y, Hagerman P (1995) Investigation of the influence of cytosine methylation on DNA flexibility. J Biol Chem 270:197–201

    Article  PubMed  CAS  Google Scholar 

  • Huntington’s Disease Collaborative Research Group (1993) A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington’s disease chromosomes. Cell 72:971–983

    Article  Google Scholar 

  • Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A (1996) Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nat Genet 13:196–202

    Article  PubMed  CAS  Google Scholar 

  • Imbert G, Saudou F, Yvert G, Devys D, Trottier Y, Gamier J-M, Weber C, Mandel J-L, Cancel G, Abbas N, Durr A, Didierjean O, Stevanin G, Agid Y, Brice A (1996) Cloning of the gene for spinocerebellar ataxia 2 reveals a locus with high sensitivity to expanded CAG/glutamine repeats. Nat Genet 14:285–291

    Article  PubMed  CAS  Google Scholar 

  • Ionov Y, Peinado M, Malkhosyan S, Shibata D, Perucho M (1993) Ubiquitous somatic mutations in simple repeated sequences reveal a new mechanism for colonie carcinogenesis. Nature 363:558–561

    Article  PubMed  CAS  Google Scholar 

  • Jacobson H, Stockmayer WH (1950) Intramolecular reaction in polycondensations. I. The theory of linear systems. J Chem Phys 18:1600–1606

    Article  CAS  Google Scholar 

  • Jaworski A, Higgins NP, Wells RD, Zacharias W (1991) Topoisomerase mutants and physiological conditions control supercoiling and Z-DNA formation in vivo. J Biol Chem 266:2576–2581

    PubMed  CAS  Google Scholar 

  • Jaworski A, Rosche WA, Gellibolian R, Kang S, Shimizu M, Sinden RR, Wells RD (1995) Mismatch repair in Escherichia coli enhances instability in vivo of (CTG)n triplet repeats from human hereditary diseases. Proc Natl Acad Sci USA 92:11019–11023

    Article  PubMed  CAS  Google Scholar 

  • Jeffreys AJ, Tamaki K, MacLeod A, Monckton DG, Neil DL, Armour JAL (1994) Complex gene conversion events in germline mutation at human minisatellites. Nat Genet 6:136–145

    Article  PubMed  CAS  Google Scholar 

  • Kahn JD, Yun E, Crothers DM (1994) Detection of localized DNA flexibility. Nature 368:163–166

    Article  PubMed  CAS  Google Scholar 

  • Kang S, Jaworski A, Ohshima K, Wells RD (1995a) Expansion and deletion of CTG triplet repeats from human disease genes are determined by the direction of replication. Nat Genet 10:213–218

    Article  PubMed  CAS  Google Scholar 

  • Kang S, Ohshima K, Shimizu M, Amirhaeri S, Wells RD (1995b) Pausing of DNA synthesis in vitro at specific loci in CTG and CGG triplet repeats from human hereditary diseases. J Biol Chem 270:27014–27021

    Article  PubMed  CAS  Google Scholar 

  • Kang S, Ohshima K, Jaworski A, Wells RD (1996) CTG triplet repeats from the myotonic dystrophy gene are expanded in E. coli distal to the replication origin as a single large event. J Mol Biol 258:543–547

    Article  PubMed  CAS  Google Scholar 

  • Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I, Kimura J, Narumiya S, Kakizuka A (1994) CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. Nat Genet 8:221–228

    Article  PubMed  CAS  Google Scholar 

  • Kinzler KW, Vogelstein B (1996) Lessons from hereditary colorectal cancer. Cell 87:159–170

    Article  PubMed  CAS  Google Scholar 

  • Koide R, Ikeuchi T, Onodera O, Tanaka H, Igarashi S, Endo K, Takahashi H, Kondo R, Ishikawa A, Hayashi T, Saito M, Tomoda A, Miike T, Naito H, Ikuta F, Tsuji S (1994) Unstable expansion of CAG repeat in hereditary dentatorubal-pallidoluysian atrophy (DRPLA). Nat Genet 6:9–13

    Article  PubMed  CAS  Google Scholar 

  • Kolodner RD (1995) Mismatch repair: mechanisms and relationship to cancer susceptibility. Trends Biochem Sci 20:397–401

    Article  PubMed  CAS  Google Scholar 

  • Krontiris TG (1995) Minisatellites and human disease. Science 269:1682–1683

    Article  PubMed  CAS  Google Scholar 

  • Kunst CB, Warren ST (1994) Cryptic and polar variation of the fragile X repeat could result in predisposing normal alleles. Cell 77:853–861

    Article  PubMed  CAS  Google Scholar 

  • LaSpada AR, Wilson EM, Lubahn DB, Harding AE, Fischbeck KH (1991) Androgen receptor gene mutations in X-linked spinal and bulbar muscular atrophy. Nature 352:77–79

    Article  CAS  Google Scholar 

  • Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki P, Sistonen P, Aaltonen LA, Nystrom-Lahti M, Guan X-Y, Zhang J, Meltzer PS, Yu J-W, Kao F-T, Chen DJ, Ce-rosaletti KM, Fournier REK, Todd S, Lewis T, Leach RJ, Naylor SL, Weissenbach J, Mecklin JP, Jarvinen H, Petersen GM, Hamilton SR, Green J, Jass J, Watson P, Lynch HT, Trent JM, de la Chapelle A, Kinzler KW, Vogelstein B (1993) Mutations of a mutS homolog in hereditary non-polyposis colorectal cancer. Cell 75:1215–1225

    Article  PubMed  CAS  Google Scholar 

  • Levinson G, Gutman GA (1987a) High frequencies of short frameshifts in poly-CA/TG tandem repeats borne by bacteriophage M13 in Escherichia coli K-12. Nucleic Acids Res 15:5323–5338

    Article  PubMed  CAS  Google Scholar 

  • Levinson G, Gutman GA (1987b) Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol 4:203–221

    PubMed  CAS  Google Scholar 

  • Li X-J, Li S-H, Sharp AH, Nucifora FC Jr, Schilling G, Lanahan A, Worley P, Snyder SH, Ross CA (1995) A huntingtin-associated protein enriched in brain with implications for pathology. Nature 378:389–402

    Google Scholar 

  • Loeb LA (1994) Microsatellite instability: marker of a mutator phenotype in cancer. Cancer Res 54:5059–5063

    PubMed  CAS  Google Scholar 

  • Lustig AJ, Petes TD (1993) Genetic control of simple sequence stability in yeast. In: Davies KE, Warren ST (eds) Genome rearrangement and stability, vol. 7, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 79–106

    Google Scholar 

  • Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barcelo J, O’Hoy K, Leblond S, Earle-Macdonald J, de Jong P, Wieringa B, Korneluk RG (1992) Myotonic dystrophy mutation: an unstable CTG repeat in the 3’ untranslated region of the gene. Science 255:1253–1255

    Article  PubMed  CAS  Google Scholar 

  • Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetheringthon C, Lawton M, Trottier Y, Lehrach H, Davies SW, Bates GP (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506

    Article  PubMed  CAS  Google Scholar 

  • Marra G, Boland CR (1995) Hereditary nonpolyposis colorectal cancer: the syndrome, the genes, and historical perspectives. J Natl Can Inst 87:1114–1125

    Article  CAS  Google Scholar 

  • Mitas M, Yu A, Dill J, Haworth IS (1995) The trinucleotide repeat sequence d(CGG)15 forms a heat-stable hairpin containing Gsyn·Ganti base pairs. Biochemistry 34:12803–12811

    Article  PubMed  CAS  Google Scholar 

  • Mitchell JE, Newbury SF, McClellan JA (1995) Compact structures of d(CNG)n oligonucleotides in solution and their possible relevance to fragile X and related human genetic diseases. Nucleic Acids Res 23:1876–1881

    Article  PubMed  CAS  Google Scholar 

  • Modrich P (1991) Mechanisms and biological effects of mismatch repair. Annu Rev Genet 25:229–253

    Article  PubMed  CAS  Google Scholar 

  • Modrich P, Lahue R (1996) Mismatch repair in replication fidelity, genetic recombination, and cancer biology. Annu Rev Biochem 65:101–133

    Article  PubMed  CAS  Google Scholar 

  • Monckton D, Coolbaugh MI, Ashizawa KT, Sicilano MJ, Caskey CT (1997) Hypermutable myot-onic dystrophy CTG repeat mouse transgenes. Nat Genet 15:193–196

    Article  PubMed  CAS  Google Scholar 

  • Monckton DG, Wong LJ, Ashizawa T, Caskey CT (1995) Somatic mosaicism, germline expansions, germline reversions and intergenerational reductions in myotonic dystrophy males: small pool PCR analyses. Hum Mol Genet 4:1–8

    Article  PubMed  CAS  Google Scholar 

  • Nagafuchi S, Yanagisawa H, Sato K, Shirayama T, Ohsaki E, Bundo M, Takeda T, Tadokoro K, Kondo I, Murayama N, Tanaka Y, Kikushima H, Umino K, Kurosawa H, Furukawa T, Nihei K, Inoue T, Sano A, Komure O, Takahashi M, Yoshizawa T, Kanazawa I, Yamada M (1994) Dentatorubral and pallidoluysian atrophy expansion of an unstable CAG trinucleotide on chromosome 12p. Nat Genet 6:14–18

    Article  PubMed  CAS  Google Scholar 

  • Nasir J, Floresco SB, O’Kusky JR, Diewert VM, Richman JM, Zeisler J, Borowski A, Marth JD, Phillips AG, Hayden MR (1995) Targeted disruption of the Huntington’s disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes. Cell 81:811–823

    Article  PubMed  CAS  Google Scholar 

  • Nasir J, Goldberg YP, Hayden MR (1996) Huntington disease: new insights into the relationship between CAG expansion and disease. Hum Mol Genet 5:1431–1435

    PubMed  CAS  Google Scholar 

  • Ohshima K, Kang S, Wells RD (1996a) CTG triplet repeats from human hereditary disease are dominant genetic expansion products in E. coli. J Biol Chem 271:1853–1856

    Article  PubMed  CAS  Google Scholar 

  • Ohshima K, Kang S, Larson JE, Wells RD (1996b) Cloning, characterization, and properties of seven triplet repeat DNA sequences. J Biol Chem 271:16773–16783

    Article  PubMed  CAS  Google Scholar 

  • Ohshima K, Kang S, Larson JE, Wells RD (1996c) TTA-TAA triplet repeats in plasmids form a non-hydrogen bonded structure. J Biol Chem 271:16784–16791

    Article  PubMed  CAS  Google Scholar 

  • Ohshima K, Wells RD (1997) Hairpin formation during DNA synthesis primer realignment in vitro in triplet repeat sequences from human hereditary disease genes. J Biol Chem 272:16798–16806

    Article  PubMed  CAS  Google Scholar 

  • Orr HT, Chung MY, Banfi S, Kwiatkowski TJ Jr, Servadio A, Beaudet AL, McCall AE, Duvick LA, Ranum LP, Zoghbi HY (1993) Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1. Nat Genet 4:221–226

    Article  PubMed  CAS  Google Scholar 

  • Parsons R, Li G-M, Longley MJ, Fang W-h, Papadopoulos N, Jen J, de la Chapelle A, Kinzler KW, Vogelstein B, Modrich P (1993) Hypermutability and mismatch repair deficiency in RER+ tumor cells. Cell 75:1227–1236

    Article  PubMed  CAS  Google Scholar 

  • Paulson HL, Fischbeck KH (1996) Trinucleotide repeats in neurogenetic disorders. Annu Rev Neurosci 19:79–107

    Article  PubMed  CAS  Google Scholar 

  • Pulst S-M, Nechiporuk A, Nechiporuk T, Gispert S, Chen X-N, Lopes-Cendes I, Pearlman S, Starkman S, Orozco-Diaz G, Lunkes A, De Jong P, Rouleau GA, Auberger G, Korenberg JR, Figueroa C, Sahba S (1996) Moderate expansion of a normally biallelic trinucleotide repeat in spinoc-erebllar ataxia type 2. Nat Genet 14:269–276

    Article  PubMed  CAS  Google Scholar 

  • Reitmair AH, Schmits R, Ewel A, Bapat B, Redston M, Mitri A, Waterhouse P, Mittrucker HW, Wakeham A, Liu B, Thomason A, Griesser H, Gallinger S, Ballhausen WG, Fishel R, Mak TW (1995) Msh2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet 11:64–70

    Article  PubMed  CAS  Google Scholar 

  • Richards RI, Sutherland GR (1992) Dynamic mutations: a new class of mutations causing human disease. Cell 70:709–712

    Article  PubMed  CAS  Google Scholar 

  • Rosche WA, Jaworski A, Kang S, Kramer SF, Larson JE, Giedroc DP, Wells RD, Sinden RR (1996) Single strand DNA binding protein enhances the stability of CTG triplet repeats in Escherichia coli. J Bacteriol 178:5042–5044

    PubMed  CAS  Google Scholar 

  • Sanpei K, Takano H, Igarashi S, Sato T, Oyake M, Sasaki H, Wakisaka A, Tashiro K, Ishida Y, Ikeuchi T, Koide R, Saito M, Sato A, Tanaka T, Hanyu S, Takiyama Y, Nishizawa M, Shimizu N, Nomura Y, Segawa M, Iwabuchi K, Eguchi I, Tanaka H, Takahashi H, Tsuji S (1996) Identification of the spinocerebellar ataxia type 2 gene using a direct identification of repeat expansion and cloning technique, DIRECT. Nat Genet 14:277–284

    Article  PubMed  CAS  Google Scholar 

  • Schleif R (1992) DNA looping. Annu Rev Biochem 61:199–223

    Article  PubMed  CAS  Google Scholar 

  • Sherman SL, Jacobs PA, Morton NE, Froster-Iskenius U, Howard-Peebles PN, Nielsen KB, Partington MW, Sutherland GR, Turner G, Watson M (1985) Further segregation analysis of the fragile X syndrome with special reference to transmitting males. Hum Genet 69:289–299

    Article  PubMed  CAS  Google Scholar 

  • Shimada J, Yamakawa H (1984) Ring-closure probability for twisted wormlike chains. Application to DNA. Macromolecules 17:689–698

    Article  CAS  Google Scholar 

  • Shimada J, Yamakawa H (1985) Statistical mechanics of DNA topoisomers. The helical worm-like chain. J Mol Biol 184:319–329

    Article  PubMed  CAS  Google Scholar 

  • Shimizu M, Gellibolian R, Oostra BA, Wells RD (1996) Cloning, characterization, and properties of plasmids containing CGG triplet repeats from the fragile X gene. J Mol Biol 258:614–626

    Article  PubMed  CAS  Google Scholar 

  • Shore D, Baldwin RL (1983a) Energetics of DNA twisting. I. Relation between twist and cyclization probability. J Mol Biol 170:957–981

    Article  PubMed  CAS  Google Scholar 

  • Shore D, Baldwin RL (1983b) Energetics of DNA twisting. II. Topoisomer analysis. J Mol Biol 170:983–1007

    Article  PubMed  CAS  Google Scholar 

  • Shore D, Langowski J, Baldwin RL (1981) DNA flexibility studied by covalent closure of short fragments into circles. Biochemistry 78:4833–4837

    CAS  Google Scholar 

  • Sinden RR (1994) DNA structure and function. Academic Press, San Diego, California

    Google Scholar 

  • Sinden RR, Wells RD (1992) DNA structure, mutations, and human genetic disease. Curr Opin Biotechnol 3:612–622

    Article  PubMed  CAS  Google Scholar 

  • Smith GK, Jie J, Fox GE, Gao X (1995) DNA CTG triplet repeats involved in dynamic mutations of neurologically related gene sequences form stable duplexes. Nucleic Acids Res 23:4303–4311

    Article  PubMed  CAS  Google Scholar 

  • Smith GP (1973) Unequal crossover and the evolution of multigene families. Cold Spring Harbor Symp Quant Biol 38:507–513

    Article  Google Scholar 

  • Strand M, Prolla TA, Liskay RM, Petes TD (1993) Destabilisation of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365:274–276

    Article  PubMed  CAS  Google Scholar 

  • Strand M, Earley MC, Crouse GF, Petes TD (1995) Mutations in the msh3 gene preferentially lead to deletions within tracts of simple repetitive DNA in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 92:10418–10421

    Article  PubMed  CAS  Google Scholar 

  • Sutherland GR, Richards RI (1995) Simple tandem DNA repeats and human genetic disease. Proc Natl Acad Sci USA 92:3636–3641

    Article  PubMed  CAS  Google Scholar 

  • Tautz D, Schlotterer C (1994) Simple sequences. Curr Opin Genet Dev 4:832–837

    Article  PubMed  CAS  Google Scholar 

  • Taylor WH, Hagerman PJ (1990) Application of the method of phage T4 DNA ligase-catalyzed ring-closure to the study of DNA structure. II. NaCl-dependence of DNA flexibility and helical repeat. J Mol Biol 212:363–376

    Article  PubMed  CAS  Google Scholar 

  • Telenius H, Kremer B, Goldberg YP, Theilmann J, Andrew SE, Zeisler J, Adam S, Greenberg C, Ives EJ, Clarke LA, Hayden MR (1994) Somatic and gonadal mosaicism of the Huntington disease gene CAG repeat in brain and sperm. Nat Genet 6:409–414

    Article  PubMed  CAS  Google Scholar 

  • Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260:816–819

    Article  PubMed  CAS  Google Scholar 

  • Trinh TQ, Sinden RR (1991) Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli. Nature 352:544–547

    Article  PubMed  CAS  Google Scholar 

  • Trottier Y, Lutz Y, Stevanin G, Imbert G, Devys D, Cancel G, Saudou F, Weber C, David G, Tora L, Agid Y, Brice A, Mandel J-L (1995) Polyglutamine expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias. Nature 378:403–406

    Article  PubMed  CAS  Google Scholar 

  • Umar A, Kunkel TA (1996) DNA-replication fidelity, mismatch repair and genome instability in cancer cells. Eur J Biochem 238:297–307

    Article  PubMed  CAS  Google Scholar 

  • Vogelstein B, Kinzler KW (1993) The multistep nature of cancer. Trends Genet 9:138–141

    Article  PubMed  CAS  Google Scholar 

  • Wang JC (1996) DNA topoisomerases. Annu Rev Biochem 65:635–692

    Article  PubMed  CAS  Google Scholar 

  • Wang JC, Davidson N (1966) On the probability of ring closure of lambda DNA. J Mol Biol 19:469–482

    Article  PubMed  CAS  Google Scholar 

  • Wang Y-H, Amirhaeri S, Kang S, Wells RD, Griffith J (1994) DNA triplet repeats from the myotonic dystrophy gene are preferential nucleosome assembly sites in vitro. Science 265:669–671

    Article  PubMed  CAS  Google Scholar 

  • Wang Y-H, Gellibolian R, Shimizu M, Wells RD, Griffith J (1996) Long repeating CCG triplet repeat blocks exclude nucleosomes: a possible mechanism for the nature of fragile sites in chromosomes. J Mol Biol 263:511–516

    Article  PubMed  CAS  Google Scholar 

  • Warren ST (1996) The expanding world of trinucleotide repeats. Science 271:1374–1375

    Article  PubMed  CAS  Google Scholar 

  • Warren ST, Ashley JCT (1995) Triplet repeat expansion mutations: the example of fragile X syndrome. Annu Rev Neurosci 18:77–99

    Article  PubMed  CAS  Google Scholar 

  • Warren ST, Nelson DL (1994) Advances in molecular analysis of fragile X syndrome. J Am Med Assoc 271:536–542

    Article  CAS  Google Scholar 

  • Wells RD (1988) Unusual DNA structures. J Biol Chem 263:1095–1098

    PubMed  CAS  Google Scholar 

  • Wells RD (1996) Molecular basis of genetic instability of triplet repeats. J Biol Chem 271:2875–2878

    PubMed  CAS  Google Scholar 

  • Wells RD (1997) Triplet repeat diseases studied in man, microbes, and molecules. Am J Psychiatry 154:887

    PubMed  CAS  Google Scholar 

  • Wells RD, Sinden RR (1993) Defined ordered sequence DNA, DNA structure, and DNA-directed mutation. In: Davis K, Warren S (eds) Genome analysis, vol 7. Genome rearrangement and stability. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 107–138

    Google Scholar 

  • Willems PJ (1994) Dynamic mutations hit double figures. Nat Genet 8:213–215

    Article  PubMed  CAS  Google Scholar 

  • Zeitlin S, Liu JP, Chapman DL, Papaioannou VE, Efstratiadis A (1995) Increased apoptosis and early embyonic lethality in mice nullizygous for the Huntington’s disease gene homologue. Nat Genet 11:155–163

    Article  PubMed  CAS  Google Scholar 

  • Zoghbi HY (1996) The expanding world of ataxins. Nat Genet 14:237–238

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Institute of Biosciences and Technology, Texas A&M University, Texas Medical Center, 2121 W. Holcombe Blvd., Houston, Texas, 77030-3303, USA

    Robert D. Wells & Albino Bacolla

  2. Imperial Cancer Research Fund, Clare Hall Laboratories, Mutagenesis Labs, Room C49, South Mims, Herts, EN6 3LD, UK

    Richard P. Bowater

Authors
  1. Robert D. Wells
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  2. Albino Bacolla
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  3. Richard P. Bowater
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Editors and Affiliations

  1. Department of Clinical Genetics, Erasmus University Rotterdam, Molewaterplein 50, 3000 DR, Rotterdam, The Netherlands

    Ben A. Oostra

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© 1998 Springer-Verlag Berlin Heidelberg

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Wells, R.D., Bacolla, A., Bowater, R.P. (1998). Instabilities of Triplet Repeats: Factors and Mechanisms. In: Oostra, B.A. (eds) Trinucleotide Diseases and Instability. Results and Problems in Cell Differentiation, vol 21. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-69680-3_4

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  • DOI: https://doi.org/10.1007/978-3-540-69680-3_4

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