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Mol Cell Biol. 1993 Sep; 13(9): 5315–5322.
PMCID: PMC360228

Inverted DNA repeats: a source of eukaryotic genomic instability.


While inverted DNA repeats are generally acknowledged to be an important source of genetic instability in prokaryotes, relatively little is known about their effects in eukaryotes. Using bacterial transposon Tn5 and its derivatives, we demonstrate that long inverted repeats also cause genetic instability leading to deletion in the yeast Saccharomyces cerevisiae. Furthermore, they induce homologous recombination. Replication plays a major role in the deletion formation. Deletions are stimulated by a mutation in the DNA polymerase delta gene (pol3). The majority of deletions result from imprecise excision between small (4- to 6-bp) repeats in a polar fashion, and they often generate quasipalindrome structures that subsequently may be highly unstable. Breakpoints are clustered near the ends of the long inverted repeats (< 150 bp). The repeats have both intra- and interchromosomal effects in that they also create hot spots for mitotic interchromosomal recombination. Intragenic recombination is 4 to 18 times more frequent for heteroalleles in which one of the two mutations is due to the insertion of a long inverted repeat, compared with other pairs of heteroalleles in which neither mutation has a long repeat. We propose that both deletion and recombination are the result of altered replication at the basal part of the stem formed by the inverted repeats.

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  • Aguilera A, Klein HL. Genetic control of intrachromosomal recombination in Saccharomyces cerevisiae. I. Isolation and genetic characterization of hyper-recombination mutations. Genetics. 1988 Aug;119(4):779–790. [PMC free article] [PubMed]
  • Auerswald EA, Ludwig G, Schaller H. Structural analysis of Tn5. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 1):107–113. [PubMed]
  • Boeke JD, LaCroute F, Fink GR. 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. [PubMed]
  • Bonneaud N, Ozier-Kalogeropoulos O, Li GY, Labouesse M, Minvielle-Sebastia L, Lacroute F. A family of low and high copy replicative, integrative and single-stranded S. cerevisiae/E. coli shuttle vectors. Yeast. 1991 Aug-Sep;7(6):609–615. [PubMed]
  • Burgers PM, Bambara RA, Campbell JL, Chang LM, Downey KM, Hübscher U, Lee MY, Linn SM, So AG, Spadari S. Revised nomenclature for eukaryotic DNA polymerases. Eur J Biochem. 1990 Aug 17;191(3):617–618. [PubMed]
  • Chattoo BB, Sherman F, Azubalis DA, Fjellstedt TA, 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. [PMC free article] [PubMed]
  • Chernov Iu O, Gordenin DA. Fenotipicheskoe proiavlenie insertsii drozhzhevogo transpozona v gene LYS2 i deletsii, voznikaiushchikh pri netochnom vyrezanii transpozona. Genetika. 1987 Jan;23(1):30–40. [PubMed]
  • Collins J. Instability of palindromic DNA in Escherichia coli. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 1):409–416. [PubMed]
  • Collins J, Volckaert G, Nevers P. Precise and nearly-precise excision of the symmetrical inverted repeats of Tn5; common features of recA-independent deletion events in Escherichia coli. Gene. 1982 Jul-Aug;19(1):139–146. [PubMed]
  • Drake JW. A constant rate of spontaneous mutation in DNA-based microbes. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7160–7164. [PMC free article] [PubMed]
  • Formosa T, Alberts BM. DNA synthesis dependent on genetic recombination: characterization of a reaction catalyzed by purified bacteriophage T4 proteins. Cell. 1986 Dec 5;47(5):793–806. [PubMed]
  • Gordenin DA, Malkova AL, Peterzen A, Kulikov VN, Pavlov YI, Perkins E, Resnick MA. Transposon Tn5 excision in yeast: influence of DNA polymerases alpha, delta, and epsilon and repair genes. Proc Natl Acad Sci U S A. 1992 May 1;89(9):3785–3789. [PMC free article] [PubMed]
  • Gordenin DA, Proscyavichus YY, Malkova AL, Trofimova MV, Peterzen A. Yeast mutants with increased bacterial transposon Tn5 excision. Yeast. 1991 Jan;7(1):37–50. [PubMed]
  • Gordenin DA, Trofimova MV, Shaburova ON, Pavlov YI, Chernoff YO, Chekuolene YV, Proscyavichus YY, Sasnauskas KV, Janulaitis AA. Precise excision of bacterial transposon Tn5 in yeast. Mol Gen Genet. 1988 Aug;213(2-3):388–393. [PubMed]
  • Henderson ST, Petes TD. Instability of a plasmid-borne inverted repeat in Saccharomyces cerevisiae. Genetics. 1993 May;134(1):57–62. [PMC free article] [PubMed]
  • Morris ME, Jinks-Robertson S. Nucleotide sequence of the LYS2 gene of Saccharomyces cerevisiae: homology to Bacillus brevis tyrocidine synthetase 1. Gene. 1991 Feb 1;98(1):141–145. [PubMed]
  • Morrison A, Araki H, Clark AB, Hamatake RK, Sugino A. A third essential DNA polymerase in S. cerevisiae. Cell. 1990 Sep 21;62(6):1143–1151. [PubMed]
  • Neil DL, Villasante A, Fisher RB, Vetrie D, Cox B, Tyler-Smith C. Structural instability of human tandemly repeated DNA sequences cloned in yeast artificial chromosome vectors. Nucleic Acids Res. 1990 Mar 25;18(6):1421–1428. [PMC free article] [PubMed]
  • Noskov VN, Tarutina MG, Pavlov Iu I, Kulikov VN, Trofimova MV, Gorbacheva AV, Chernov Iu O, Sasnauskas KV, Neistat MA, Tolstorukov II, et al. Razrabotka sistemy vnutrigennogo kartirovaniia dlia molekuliarno- geneticheskogo analiza mutatsii v gene LYS2 u drozhzhei sakharomitsetov. Genetika. 1990 Jul;26(7):1161–1168. [PubMed]
  • Ohshima A, Inouye S, Inouye M. In vivo duplication of genetic elements by the formation of stem-loop DNA without an RNA intermediate. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1016–1020. [PMC free article] [PubMed]
  • Ruskin B, Fink GR. Mutations in POL1 increase the mitotic instability of tandem inverted repeats in Saccharomyces cerevisiae. Genetics. 1993 May;134(1):43–56. [PMC free article] [PubMed]
  • Tindall KR, Stankowski LF., Jr Molecular analysis of spontaneous mutations at the gpt locus in Chinese hamster ovary (AS52) cells. Mutat Res. 1989 Mar-May;220(2-3):241–253. [PubMed]
  • Trinh TQ, Sinden RR. Preferential DNA secondary structure mutagenesis in the lagging strand of replication in E. coli. Nature. 1991 Aug 8;352(6335):544–547. [PubMed]
  • Vincent A, Petes TD. Mitotic and meiotic gene conversion of Ty elements and other insertions in Saccharomyces cerevisiae. Genetics. 1989 Aug;122(4):759–772. [PMC free article] [PubMed]
  • Voelkel-Meiman K, Roeder GS. A chromosome containing HOT1 preferentially receives information during mitotic interchromosomal gene conversion. Genetics. 1990 Mar;124(3):561–572. [PMC free article] [PubMed]
  • Wang TS. Eukaryotic DNA polymerases. Annu Rev Biochem. 1991;60:513–552. [PubMed]

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