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. 1995 Mar 28;92(7):2667–2671. doi: 10.1073/pnas.92.7.2667

Effects of yeast DNA topoisomerase III on telomere structure.

R A Kim 1, P R Caron 1, J C Wang 1
PMCID: PMC42279  PMID: 7708702

Abstract

The yeast TOP3 gene, encoding DNA topoisomerase III, and EST1 gene, encoding a putative telomerase, are shown to be abutted head-to-head on chromosome XII, with the two initiation codons separated by 258 bp. This arrangement suggests that the two genes might share common upstream regulatory sequences and that their products might be functionally related. A comparison of isogenic pairs of yeast TOP3+ and delta top3 strains indicates that the G1-3T repetitive sequence tracks in delta top3 cells are significantly shortened, by about 150 bp. Cells lacking topoisomerase III also show a much higher sequence fluidity in the subtelomeric regions. In delta top3 cells, clusters of two or more copies of tandemly arranged Y' elements have a high tendency of disappearing due to the loss or dispersion of the elements; similarly, a URA3 marker embedded in a Y' element close to the chromosomal tip shows a much higher rate of being lost relative to that in TOP3+ cells. These results suggest that yeast DNA topoisomerase III might affect telomere stability, and plausible mechanisms are discussed.

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Selected References

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

  1. Adachi Y., Luke M., Laemmli U. K. Chromosome assembly in vitro: topoisomerase II is required for condensation. Cell. 1991 Jan 11;64(1):137–148. doi: 10.1016/0092-8674(91)90215-k. [DOI] [PubMed] [Google Scholar]
  2. Blackburn E. H. Structure and function of telomeres. Nature. 1991 Apr 18;350(6319):569–573. doi: 10.1038/350569a0. [DOI] [PubMed] [Google Scholar]
  3. Blackburn E. H. Telomeres: no end in sight. Cell. 1994 Jun 3;77(5):621–623. doi: 10.1016/0092-8674(94)90046-9. [DOI] [PubMed] [Google Scholar]
  4. Blackburn E. H. The molecular structure of centromeres and telomeres. Annu Rev Biochem. 1984;53:163–194. doi: 10.1146/annurev.bi.53.070184.001115. [DOI] [PubMed] [Google Scholar]
  5. Boy de la Tour E., Laemmli U. K. The metaphase scaffold is helically folded: sister chromatids have predominantly opposite helical handedness. Cell. 1988 Dec 23;55(6):937–944. doi: 10.1016/0092-8674(88)90239-5. [DOI] [PubMed] [Google Scholar]
  6. Caron P. R., Wang J. C. Appendix. II: Alignment of primary sequences of DNA topoisomerases. Adv Pharmacol. 1994;29B:271–297. doi: 10.1016/s1054-3589(08)61143-6. [DOI] [PubMed] [Google Scholar]
  7. Carson M. J., Hartwell L. CDC17: an essential gene that prevents telomere elongation in yeast. Cell. 1985 Aug;42(1):249–257. doi: 10.1016/s0092-8674(85)80120-3. [DOI] [PubMed] [Google Scholar]
  8. Champoux J. J. Mechanism of catalysis by eukaryotic DNA topoisomerase I. Adv Pharmacol. 1994;29A:71–82. doi: 10.1016/s1054-3589(08)60540-2. [DOI] [PubMed] [Google Scholar]
  9. Chan C. S., Tye B. K. Organization of DNA sequences and replication origins at yeast telomeres. Cell. 1983 Jun;33(2):563–573. doi: 10.1016/0092-8674(83)90437-3. [DOI] [PubMed] [Google Scholar]
  10. Christman M. F., Dietrich F. S., Fink G. R. Mitotic recombination in the rDNA of S. cerevisiae is suppressed by the combined action of DNA topoisomerases I and II. Cell. 1988 Nov 4;55(3):413–425. doi: 10.1016/0092-8674(88)90027-x. [DOI] [PubMed] [Google Scholar]
  11. Cockerill P. N., Garrard W. T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell. 1986 Jan 31;44(2):273–282. doi: 10.1016/0092-8674(86)90761-0. [DOI] [PubMed] [Google Scholar]
  12. DiGate R. J., Marians K. J. Escherichia coli topoisomerase III-catalyzed cleavage of RNA. J Biol Chem. 1992 Oct 15;267(29):20532–20535. [PubMed] [Google Scholar]
  13. Dunn B., Szauter P., Pardue M. L., Szostak J. W. Transfer of yeast telomeres to linear plasmids by recombination. Cell. 1984 Nov;39(1):191–201. doi: 10.1016/0092-8674(84)90205-8. [DOI] [PubMed] [Google Scholar]
  14. Gangloff S., McDonald J. P., Bendixen C., Arthur L., Rothstein R. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol. 1994 Dec;14(12):8391–8398. doi: 10.1128/mcb.14.12.8391. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Gottschling D. E., Aparicio O. M., Billington B. L., Zakian V. A. Position effect at S. cerevisiae telomeres: reversible repression of Pol II transcription. Cell. 1990 Nov 16;63(4):751–762. doi: 10.1016/0092-8674(90)90141-z. [DOI] [PubMed] [Google Scholar]
  16. Hirano T., Mitchison T. J. Topoisomerase II does not play a scaffolding role in the organization of mitotic chromosomes assembled in Xenopus egg extracts. J Cell Biol. 1993 Feb;120(3):601–612. doi: 10.1083/jcb.120.3.601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Horowitz H., Haber J. E. Identification of autonomously replicating circular subtelomeric Y' elements in Saccharomyces cerevisiae. Mol Cell Biol. 1985 Sep;5(9):2369–2380. doi: 10.1128/mcb.5.9.2369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Horowitz H., Thorburn P., Haber J. E. Rearrangements of highly polymorphic regions near telomeres of Saccharomyces cerevisiae. Mol Cell Biol. 1984 Nov;4(11):2509–2517. doi: 10.1128/mcb.4.11.2509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z., Favello A., Fulton L., Gattung S. Complete nucleotide sequence of Saccharomyces cerevisiae chromosome VIII. Science. 1994 Sep 30;265(5181):2077–2082. doi: 10.1126/science.8091229. [DOI] [PubMed] [Google Scholar]
  20. Jäger D., Philippsen P. Many yeast chromosomes lack the telomere-specific Y' sequence. Mol Cell Biol. 1989 Dec;9(12):5754–5757. doi: 10.1128/mcb.9.12.5754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kim R. A., Wang J. C. A subthreshold level of DNA topoisomerases leads to the excision of yeast rDNA as extrachromosomal rings. Cell. 1989 Jun 16;57(6):975–985. doi: 10.1016/0092-8674(89)90336-x. [DOI] [PubMed] [Google Scholar]
  22. Kim R. A., Wang J. C. Identification of the yeast TOP3 gene product as a single strand-specific DNA topoisomerase. J Biol Chem. 1992 Aug 25;267(24):17178–17185. [PubMed] [Google Scholar]
  23. Kodadek T. Inhibition of protein-mediated homologous pairing by a DNA helicase. J Biol Chem. 1991 May 25;266(15):9712–9718. [PubMed] [Google Scholar]
  24. Louis E. J., Haber J. E. Mitotic recombination among subtelomeric Y' repeats in Saccharomyces cerevisiae. Genetics. 1990 Mar;124(3):547–559. doi: 10.1093/genetics/124.3.547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Louis E. J., Haber J. E. The structure and evolution of subtelomeric Y' repeats in Saccharomyces cerevisiae. Genetics. 1992 Jul;131(3):559–574. doi: 10.1093/genetics/131.3.559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Louis E. J., Haber J. E. The subtelomeric Y' repeat family in Saccharomyces cerevisiae: an experimental system for repeated sequence evolution. Genetics. 1990 Mar;124(3):533–545. doi: 10.1093/genetics/124.3.533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lundblad V., Blackburn E. H. An alternative pathway for yeast telomere maintenance rescues est1- senescence. Cell. 1993 Apr 23;73(2):347–360. doi: 10.1016/0092-8674(93)90234-h. [DOI] [PubMed] [Google Scholar]
  28. Lundblad V., Szostak J. W. A mutant with a defect in telomere elongation leads to senescence in yeast. Cell. 1989 May 19;57(4):633–643. doi: 10.1016/0092-8674(89)90132-3. [DOI] [PubMed] [Google Scholar]
  29. Lustig A. J., Petes T. D. Identification of yeast mutants with altered telomere structure. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1398–1402. doi: 10.1073/pnas.83.5.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Morel P., Hejna J. A., Ehrlich S. D., Cassuto E. Antipairing and strand transferase activities of E. coli helicase II (UvrD). Nucleic Acids Res. 1993 Jul 11;21(14):3205–3209. doi: 10.1093/nar/21.14.3205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Newport J. Nuclear reconstitution in vitro: stages of assembly around protein-free DNA. Cell. 1987 Jan 30;48(2):205–217. doi: 10.1016/0092-8674(87)90424-7. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Singer M. S., Gottschling D. E. TLC1: template RNA component of Saccharomyces cerevisiae telomerase. Science. 1994 Oct 21;266(5184):404–409. doi: 10.1126/science.7545955. [DOI] [PubMed] [Google Scholar]
  34. Slesarev A. I., Stetter K. O., Lake J. A., Gellert M., Krah R., Kozyavkin S. A. DNA topoisomerase V is a relative of eukaryotic topoisomerase I from a hyperthermophilic prokaryote. Nature. 1993 Aug 19;364(6439):735–737. doi: 10.1038/364735a0. [DOI] [PubMed] [Google Scholar]
  35. Swedlow J. R., Sedat J. W., Agard D. A. Multiple chromosomal populations of topoisomerase II detected in vivo by time-lapse, three-dimensional wide-field microscopy. Cell. 1993 Apr 9;73(1):97–108. doi: 10.1016/0092-8674(93)90163-k. [DOI] [PubMed] [Google Scholar]
  36. Szostak J. W., Blackburn E. H. Cloning yeast telomeres on linear plasmid vectors. Cell. 1982 May;29(1):245–255. doi: 10.1016/0092-8674(82)90109-x. [DOI] [PubMed] [Google Scholar]
  37. Thaler D. S., Sampson E., Siddiqi I., Rosenberg S. M., Thomason L. C., Stahl F. W., Stahl M. M. Recombination of bacteriophage lambda in recD mutants of Escherichia coli. Genome. 1989;31(1):53–67. doi: 10.1139/g89-013. [DOI] [PubMed] [Google Scholar]
  38. Uemura T., Ohkura H., Adachi Y., Morino K., Shiozaki K., Yanagida M. DNA topoisomerase II is required for condensation and separation of mitotic chromosomes in S. pombe. Cell. 1987 Sep 11;50(6):917–925. doi: 10.1016/0092-8674(87)90518-6. [DOI] [PubMed] [Google Scholar]
  39. Wallis J. W., Chrebet G., Brodsky G., Rolfe M., Rothstein R. A hyper-recombination mutation in S. cerevisiae identifies a novel eukaryotic topoisomerase. Cell. 1989 Jul 28;58(2):409–419. doi: 10.1016/0092-8674(89)90855-6. [DOI] [PubMed] [Google Scholar]
  40. Walmsley R. M., Petes T. D. Genetic control of chromosome length in yeast. Proc Natl Acad Sci U S A. 1985 Jan;82(2):506–510. doi: 10.1073/pnas.82.2.506. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. Wang J. C., Caron P. R., Kim R. A. The role of DNA topoisomerases in recombination and genome stability: a double-edged sword? Cell. 1990 Aug 10;62(3):403–406. doi: 10.1016/0092-8674(90)90002-v. [DOI] [PubMed] [Google Scholar]
  44. Wang J. C. DNA topoisomerases. Annu Rev Biochem. 1985;54:665–697. doi: 10.1146/annurev.bi.54.070185.003313. [DOI] [PubMed] [Google Scholar]
  45. Wang J. C. DNA topoisomerases: why so many? J Biol Chem. 1991 Apr 15;266(11):6659–6662. [PubMed] [Google Scholar]
  46. Zakian V. A., Blanton H. M. Distribution of telomere-associated sequences on natural chromosomes in Saccharomyces cerevisiae. Mol Cell Biol. 1988 May;8(5):2257–2260. doi: 10.1128/mcb.8.5.2257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Zakian V. A. Structure and function of telomeres. Annu Rev Genet. 1989;23:579–604. doi: 10.1146/annurev.ge.23.120189.003051. [DOI] [PubMed] [Google Scholar]

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