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. 1992 Jun;12(6):2749–2757. doi: 10.1128/mcb.12.6.2749

Instability of simple sequence DNA in Saccharomyces cerevisiae.

S T Henderson 1, T D Petes 1
PMCID: PMC364469  PMID: 1588966

Abstract

All eukaryotic genomes thus far examined contain simple sequence repeats. A particularly common simple sequence in many organisms (including humans) consists of tracts of alternating GT residues on one strand. Allelic poly(GT) tracts are often of different lengths in different individuals, indicating that they are likely to be unstable. We examined the instability of poly(GT) and poly(G) tracts in the yeast Saccharomyces cerevisiae. We found that these tracts were dramatically unstable, altering length at a minimal rate of 10(-4) events per division. Most of the changes involved one or two repeat unit additions or deletions, although one alteration involved an interaction with the yeast telomeres.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahn B. Y., Dornfeld K. J., Fagrelius T. J., Livingston D. M. Effect of limited homology on gene conversion in a Saccharomyces cerevisiae plasmid recombination system. Mol Cell Biol. 1988 Jun;8(6):2442–2448. doi: 10.1128/mcb.8.6.2442. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alani E., Kleckner N. A new type of fusion analysis applicable to many organisms: protein fusions to the URA3 gene of yeast. Genetics. 1987 Sep;117(1):5–12. doi: 10.1093/genetics/117.1.5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berg D. T., Walls J. D., Reifel-Miller A. E., Grinnell B. W. E1A-induced enhancer activity of the poly(dG-dT).poly(dA-dC) element (GT element) and interactions with a GT-specific nuclear factor. Mol Cell Biol. 1989 Nov;9(11):5248–5253. doi: 10.1128/mcb.9.11.5248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Boeke J. D., LaCroute F., Fink G. R. A positive selection for mutants lacking orotidine-5'-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistance. Mol Gen Genet. 1984;197(2):345–346. doi: 10.1007/BF00330984. [DOI] [PubMed] [Google Scholar]
  5. Boeke J. D., Trueheart J., Natsoulis G., Fink G. R. 5-Fluoroorotic acid as a selective agent in yeast molecular genetics. Methods Enzymol. 1987;154:164–175. doi: 10.1016/0076-6879(87)54076-9. [DOI] [PubMed] [Google Scholar]
  6. Chattoo B. B., Sherman F., Azubalis D. A., Fjellstedt T. A., Mehnert D., Ogur M. Selection of lys2 Mutants of the Yeast SACCHAROMYCES CEREVISIAE by the Utilization of alpha-AMINOADIPATE. Genetics. 1979 Sep;93(1):51–65. doi: 10.1093/genetics/93.1.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Das G., Consaul S., Sherman F. A highly revertible cyc1 mutant of yeast contains a small tandem duplication. Genetics. 1988 Sep;120(1):57–62. doi: 10.1093/genetics/120.1.57. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Farabaugh P. J., Schmeissner U., Hofer M., Miller J. H. Genetic studies of the lac repressor. VII. On the molecular nature of spontaneous hotspots in the lacI gene of Escherichia coli. J Mol Biol. 1978 Dec 25;126(4):847–857. doi: 10.1016/0022-2836(78)90023-2. [DOI] [PubMed] [Google Scholar]
  9. Fleig U. N., Pridmore R. D., Philippsen P. Construction of LYS2 cartridges for use in genetic manipulations of Saccharomyces cerevisiae. Gene. 1986;46(2-3):237–245. doi: 10.1016/0378-1119(86)90408-7. [DOI] [PubMed] [Google Scholar]
  10. Fogel S., Welch J. W., Louis E. J. Meiotic gene conversion mediates gene amplification in yeast. Cold Spring Harb Symp Quant Biol. 1984;49:55–65. doi: 10.1101/sqb.1984.049.01.009. [DOI] [PubMed] [Google Scholar]
  11. Freund A. M., Bichara M., Fuchs R. P. Z-DNA-forming sequences are spontaneous deletion hot spots. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7465–7469. doi: 10.1073/pnas.86.19.7465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hamada H., Petrino M. G., Kakunaga T. A novel repeated element with Z-DNA-forming potential is widely found in evolutionarily diverse eukaryotic genomes. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6465–6469. doi: 10.1073/pnas.79.21.6465. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hoffman C. S., Winston F. A ten-minute DNA preparation from yeast efficiently releases autonomous plasmids for transformation of Escherichia coli. Gene. 1987;57(2-3):267–272. doi: 10.1016/0378-1119(87)90131-4. [DOI] [PubMed] [Google Scholar]
  14. Jaworski A., Blaho J. A., Larson J. E., Shimizu M., Wells R. D. Tetracycline promoter mutations decrease non-B DNA structural transitions, negative linking differences and deletions in recombinant plasmids in Escherichia coli. J Mol Biol. 1989 Jun 5;207(3):513–526. doi: 10.1016/0022-2836(89)90461-0. [DOI] [PubMed] [Google Scholar]
  15. Kashi Y., Tikochinsky Y., Genislav E., Iraqi F., Nave A., Beckmann J. S., Gruenbaum Y., Soller M. Large restriction fragments containing poly-TG are highly polymorphic in a variety of vertebrates. Nucleic Acids Res. 1990 Mar 11;18(5):1129–1132. doi: 10.1093/nar/18.5.1129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kraft R., Tardiff J., Krauter K. S., Leinwand L. A. Using mini-prep plasmid DNA for sequencing double stranded templates with Sequenase. Biotechniques. 1988 Jun;6(6):544-6, 549. [PubMed] [Google Scholar]
  17. Kreitman M., Landweber L. F. A strategy for producing single-stranded DNA in the polymerase chain reaction. A direct method for genomic sequencing. Gene Anal Tech. 1989 Jul-Aug;6(4):84–88. doi: 10.1016/0735-0651(89)90021-6. [DOI] [PubMed] [Google Scholar]
  18. Kunkel T. A. Frameshift mutagenesis by eucaryotic DNA polymerases in vitro. J Biol Chem. 1986 Oct 15;261(29):13581–13587. [PubMed] [Google Scholar]
  19. Kunkel T. A., Hamatake R. K., Motto-Fox J., Fitzgerald M. P., Sugino A. Fidelity of DNA polymerase I and the DNA polymerase I-DNA primase complex from Saccharomyces cerevisiae. Mol Cell Biol. 1989 Oct;9(10):4447–4458. doi: 10.1128/mcb.9.10.4447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kurnit D. M. Escherichia coli recA deletion strains that are highly competent for transformation and for in vivo phage packaging. Gene. 1989 Oct 30;82(2):313–315. doi: 10.1016/0378-1119(89)90056-5. [DOI] [PubMed] [Google Scholar]
  21. Levinson G., Gutman G. A. High frequencies of short frameshifts in poly-CA/TG tandem repeats borne by bacteriophage M13 in Escherichia coli K-12. Nucleic Acids Res. 1987 Jul 10;15(13):5323–5338. doi: 10.1093/nar/15.13.5323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Levinson G., Gutman G. A. Slipped-strand mispairing: a major mechanism for DNA sequence evolution. Mol Biol Evol. 1987 May;4(3):203–221. doi: 10.1093/oxfordjournals.molbev.a040442. [DOI] [PubMed] [Google Scholar]
  23. Lowenhaupt K., Rich A., Pardue M. L. Nonrandom distribution of long mono- and dinucleotide repeats in Drosophila chromosomes: correlations with dosage compensation, heterochromatin, and recombination. Mol Cell Biol. 1989 Mar;9(3):1173–1182. doi: 10.1128/mcb.9.3.1173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Luria S. E., Delbrück M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics. 1943 Nov;28(6):491–511. doi: 10.1093/genetics/28.6.491. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Naylor L. H., Clark E. M. d(TG)n.d(CA)n sequences upstream of the rat prolactin gene form Z-DNA and inhibit gene transcription. Nucleic Acids Res. 1990 Mar 25;18(6):1595–1601. doi: 10.1093/nar/18.6.1595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Petes T. D., Hill C. W. Recombination between repeated genes in microorganisms. Annu Rev Genet. 1988;22:147–168. doi: 10.1146/annurev.ge.22.120188.001051. [DOI] [PubMed] [Google Scholar]
  27. Petes T. D. Unequal meiotic recombination within tandem arrays of yeast ribosomal DNA genes. Cell. 1980 Mar;19(3):765–774. doi: 10.1016/s0092-8674(80)80052-3. [DOI] [PubMed] [Google Scholar]
  28. Pluta A. F., Zakian V. A. Recombination occurs during telomere formation in yeast. Nature. 1989 Feb 2;337(6206):429–433. doi: 10.1038/337429a0. [DOI] [PubMed] [Google Scholar]
  29. Rich A., Nordheim A., Wang A. H. The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem. 1984;53:791–846. doi: 10.1146/annurev.bi.53.070184.004043. [DOI] [PubMed] [Google Scholar]
  30. Ripley L. S. Frameshift mutation: determinants of specificity. Annu Rev Genet. 1990;24:189–213. doi: 10.1146/annurev.ge.24.120190.001201. [DOI] [PubMed] [Google Scholar]
  31. Rose M. D., Broach J. R. Cloning genes by complementation in yeast. Methods Enzymol. 1991;194:195–230. doi: 10.1016/0076-6879(91)94017-7. [DOI] [PubMed] [Google Scholar]
  32. Rose M., Botstein D. Construction and use of gene fusions to lacZ (beta-galactosidase) that are expressed in yeast. Methods Enzymol. 1983;101:167–180. doi: 10.1016/0076-6879(83)01012-5. [DOI] [PubMed] [Google Scholar]
  33. Rothstein R. J. One-step gene disruption in yeast. Methods Enzymol. 1983;101:202–211. doi: 10.1016/0076-6879(83)01015-0. [DOI] [PubMed] [Google Scholar]
  34. Santoro C., Costanzo F., Ciliberto G. Inhibition of eukaryotic tRNA transcription by potential Z-DNA sequences. EMBO J. 1984 Jul;3(7):1553–1559. doi: 10.1002/j.1460-2075.1984.tb02010.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Shampay J., Szostak J. W., Blackburn E. H. DNA sequences of telomeres maintained in yeast. Nature. 1984 Jul 12;310(5973):154–157. doi: 10.1038/310154a0. [DOI] [PubMed] [Google Scholar]
  36. Slightom J. L., Blechl A. E., Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. doi: 10.1016/0092-8674(80)90426-2. [DOI] [PubMed] [Google Scholar]
  37. Stillman B. Initiation of eukaryotic DNA replication in vitro. Bioessays. 1988 Aug-Sep;9(2-3):56–60. doi: 10.1002/bies.950090205. [DOI] [PubMed] [Google Scholar]
  38. Streisinger G., Okada Y., Emrich J., Newton J., Tsugita A., Terzaghi E., Inouye M. Frameshift mutations and the genetic code. This paper is dedicated to Professor Theodosius Dobzhansky on the occasion of his 66th birthday. Cold Spring Harb Symp Quant Biol. 1966;31:77–84. doi: 10.1101/sqb.1966.031.01.014. [DOI] [PubMed] [Google Scholar]
  39. Stringer J. R. Recombination between poly[d(GT).d(CA)] sequences in simian virus 40-infected cultured cells. Mol Cell Biol. 1985 Jun;5(6):1247–1259. doi: 10.1128/mcb.5.6.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Szostak J. W., Wu R. Unequal crossing over in the ribosomal DNA of Saccharomyces cerevisiae. Nature. 1980 Apr 3;284(5755):426–430. doi: 10.1038/284426a0. [DOI] [PubMed] [Google Scholar]
  41. Tautz D. Genomic finger printing goes simple. Bioessays. 1990 Jan;12(1):44–46. doi: 10.1002/bies.950120111. [DOI] [PubMed] [Google Scholar]
  42. Tautz D., Trick M., Dover G. A. Cryptic simplicity in DNA is a major source of genetic variation. Nature. 1986 Aug 14;322(6080):652–656. doi: 10.1038/322652a0. [DOI] [PubMed] [Google Scholar]
  43. Treco D., Arnheim N. The evolutionarily conserved repetitive sequence d(TG.AC)n promotes reciprocal exchange and generates unusual recombinant tetrads during yeast meiosis. Mol Cell Biol. 1986 Nov;6(11):3934–3947. doi: 10.1128/mcb.6.11.3934. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Walmsley R. M., Szostak J. W., Petes T. D. Is there left-handed DNA at the ends of yeast chromosomes? Nature. 1983 Mar 3;302(5903):84–86. doi: 10.1038/302084a0. [DOI] [PubMed] [Google Scholar]
  45. Walmsley R. W., Chan C. S., Tye B. K., Petes T. D. Unusual DNA sequences associated with the ends of yeast chromosomes. Nature. 1984 Jul 12;310(5973):157–160. doi: 10.1038/310157a0. [DOI] [PubMed] [Google Scholar]
  46. Weber J. L., May P. E. Abundant class of human DNA polymorphisms which can be typed using the polymerase chain reaction. Am J Hum Genet. 1989 Mar;44(3):388–396. [PMC free article] [PubMed] [Google Scholar]
  47. Weiss R. B., Dunn D. M., Atkins J. F., Gesteland R. F. Slippery runs, shifty stops, backward steps, and forward hops: -2, -1, +1, +2, +5, and +6 ribosomal frameshifting. Cold Spring Harb Symp Quant Biol. 1987;52:687–693. doi: 10.1101/sqb.1987.052.01.078. [DOI] [PubMed] [Google Scholar]
  48. Weston-Hafer K., Berg D. E. Deletions in plasmid pBR322: replication slippage involving leading and lagging strands. Genetics. 1991 Apr;127(4):649–655. doi: 10.1093/genetics/127.4.649. [DOI] [PMC free article] [PubMed] [Google Scholar]

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