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. 2002 Jan;160(1):235–245. doi: 10.1093/genetics/160.1.235

Telomere elongation (Tel), a new mutation in Drosophila melanogaster that produces long telomeres.

Giorgia M Siriaco 1, Giovanni Cenci 1, Abdelali Haoudi 1, Larry E Champion 1, Chun Zhou 1, Maurizio Gatti 1, James M Mason 1
PMCID: PMC1461955  PMID: 11805059

Abstract

In most eukaryotes telomeres are extended by telomerase. Drosophila melanogaster, however, lacks telomerase, and telomere-specific non-LTR retrotransposons, HeT-A and TART, transpose specifically to chromosome ends. A Drosophila strain, Gaiano, that has long telomeres has been identified. We extracted the major Gaiano chromosomes into an Oregon-R genetic background and examined the resulting stocks after 60 generations. In situ hybridization using HeT-A and TART sequences showed that, in stocks carrying either the X or the second chromosome from Gaiano, only the Gaiano-derived chromosomes display long telomeres. However, in stocks carrying the Gaiano third chromosome, all telomeres are substantially elongated, indicating that the Gaiano chromosome 3 carries a factor that increases HeT-A and TART addition to the telomeres. We show that this factor, termed Telomere elongation (Tel), is dominant and localizes as a single unit to 69 on the genetic map. The long telomeres tend to associate with each other in both polytene and mitotic cells. These associations depend on telomere length rather than the presence of Tel. Associations between metaphase chromosomes are resolved during anaphase, suggesting that they are mediated by either proteinaceous links or DNA hydrogen bonding, rather than covalent DNA-DNA bonds.

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Selected References

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  1. Biessmann H., Champion L. E., O'Hair M., Ikenaga K., Kasravi B., Mason J. M. Frequent transpositions of Drosophila melanogaster HeT-A transposable elements to receding chromosome ends. EMBO J. 1992 Dec;11(12):4459–4469. doi: 10.1002/j.1460-2075.1992.tb05547.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Biessmann H., Kasravi B., Bui T., Fujiwara G., Champion L. E., Mason J. M. Comparison of two active HeT-A retroposons of Drosophila melanogaster. Chromosoma. 1994 Apr;103(2):90–98. doi: 10.1007/BF00352317. [DOI] [PubMed] [Google Scholar]
  3. Biessmann H., Mason J. M., Ferry K., d'Hulst M., Valgeirsdottir K., Traverse K. L., Pardue M. L. Addition of telomere-associated HeT DNA sequences "heals" broken chromosome ends in Drosophila. Cell. 1990 May 18;61(4):663–673. doi: 10.1016/0092-8674(90)90478-w. [DOI] [PubMed] [Google Scholar]
  4. Biessmann H., Zurovcova M., Yao J. G., Lozovskaya E., Walter M. F. A telomeric satellite in Drosophila virilis and its sibling species. Chromosoma. 2000 Sep;109(6):372–380. doi: 10.1007/s004120000094. [DOI] [PubMed] [Google Scholar]
  5. Biessmann H., Zurovcova M., Yao J. G., Lozovskaya E., Walter M. F. A telomeric satellite in Drosophila virilis and its sibling species. Chromosoma. 2000 Sep;109(6):372–380. doi: 10.1007/s004120000094. [DOI] [PubMed] [Google Scholar]
  6. Bodnar A. G., Ouellette M., Frolkis M., Holt S. E., Chiu C. P., Morin G. B., Harley C. B., Shay J. W., Lichtsteiner S., Wright W. E. Extension of life-span by introduction of telomerase into normal human cells. Science. 1998 Jan 16;279(5349):349–352. doi: 10.1126/science.279.5349.349. [DOI] [PubMed] [Google Scholar]
  7. Bryan T. M., Englezou A., Gupta J., Bacchetti S., Reddel R. R. Telomere elongation in immortal human cells without detectable telomerase activity. EMBO J. 1995 Sep 1;14(17):4240–4248. doi: 10.1002/j.1460-2075.1995.tb00098.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bryan T. M., Marusic L., Bacchetti S., Namba M., Reddel R. R. The telomere lengthening mechanism in telomerase-negative immortal human cells does not involve the telomerase RNA subunit. Hum Mol Genet. 1997 Jun;6(6):921–926. doi: 10.1093/hmg/6.6.921. [DOI] [PubMed] [Google Scholar]
  9. Cenci G., Rawson R. B., Belloni G., Castrillon D. H., Tudor M., Petrucci R., Goldberg M. L., Wasserman S. A., Gatti M. UbcD1, a Drosophila ubiquitin-conjugating enzyme required for proper telomere behavior. Genes Dev. 1997 Apr 1;11(7):863–875. doi: 10.1101/gad.11.7.863. [DOI] [PubMed] [Google Scholar]
  10. Danilevskaya O., Lofsky A., Kurenova E. V., Pardue M. L. The Y chromosome of Drosophila melanogaster contains a distinctive subclass of Het-A-related repeats. Genetics. 1993 Jun;134(2):531–543. doi: 10.1093/genetics/134.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Danilevskaya O., Slot F., Pavlova M., Pardue M. L. Structure of the Drosophila HeT-A transposon: a retrotransposon-like element forming telomeres. Chromosoma. 1994 Jun;103(3):215–224. doi: 10.1007/BF00368015. [DOI] [PubMed] [Google Scholar]
  12. Dunham M. A., Neumann A. A., Fasching C. L., Reddel R. R. Telomere maintenance by recombination in human cells. Nat Genet. 2000 Dec;26(4):447–450. doi: 10.1038/82586. [DOI] [PubMed] [Google Scholar]
  13. Eickbush T. H. Telomerase and retrotransposons: which came first? Science. 1997 Aug 15;277(5328):911–912. doi: 10.1126/science.277.5328.911. [DOI] [PubMed] [Google Scholar]
  14. Eissenberg J. C. Position effect variegation in Drosophila: towards a genetics of chromatin assembly. Bioessays. 1989 Jul;11(1):14–17. doi: 10.1002/bies.950110105. [DOI] [PubMed] [Google Scholar]
  15. Engels W. R., Preston C. R., Thompson P., Eggleston W. B. In situ hybridization of Drosophila polytene chromosomes with digoxigenin-dUTP-labeled probes. Trends Genet. 1989 Nov;5(11):366–366. doi: 10.1016/0168-9525(89)90170-4. [DOI] [PubMed] [Google Scholar]
  16. Fanti L., Giovinazzo G., Berloco M., Pimpinelli S. The heterochromatin protein 1 prevents telomere fusions in Drosophila. Mol Cell. 1998 Nov;2(5):527–538. doi: 10.1016/s1097-2765(00)80152-5. [DOI] [PubMed] [Google Scholar]
  17. Gatti M., Bonaccorsi S., Pimpinelli S. Looking at Drosophila mitotic chromosomes. Methods Cell Biol. 1994;44:371–391. doi: 10.1016/s0091-679x(08)60924-3. [DOI] [PubMed] [Google Scholar]
  18. Gatti M., Goldberg M. L. Mutations affecting cell division in Drosophila. Methods Cell Biol. 1991;35:543–586. doi: 10.1016/s0091-679x(08)60587-7. [DOI] [PubMed] [Google Scholar]
  19. Golubovsky M. D., Konev A. Y., Walter M. F., Biessmann H., Mason J. M. Terminal retrotransposons activate a subtelomeric white transgene at the 2L telomere in Drosophila. Genetics. 2001 Jul;158(3):1111–1123. doi: 10.1093/genetics/158.3.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Griffith J. D., Comeau L., Rosenfield S., Stansel R. M., Bianchi A., Moss H., de Lange T. Mammalian telomeres end in a large duplex loop. Cell. 1999 May 14;97(4):503–514. doi: 10.1016/s0092-8674(00)80760-6. [DOI] [PubMed] [Google Scholar]
  21. Hande M. P., Samper E., Lansdorp P., Blasco M. A. Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. J Cell Biol. 1999 Feb 22;144(4):589–601. doi: 10.1083/jcb.144.4.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Hande P., Slijepcevic P., Silver A., Bouffler S., van Buul P., Bryant P., Lansdorp P. Elongated telomeres in scid mice. Genomics. 1999 Mar 1;56(2):221–223. doi: 10.1006/geno.1998.5668. [DOI] [PubMed] [Google Scholar]
  23. James T. C., Eissenberg J. C., Craig C., Dietrich V., Hobson A., Elgin S. C. Distribution patterns of HP1, a heterochromatin-associated nonhistone chromosomal protein of Drosophila. Eur J Cell Biol. 1989 Oct;50(1):170–180. [PubMed] [Google Scholar]
  24. Jeggo P. A. DNA-PK: at the cross-roads of biochemistry and genetics. Mutat Res. 1997 Jun 9;384(1):1–14. doi: 10.1016/s0921-8777(97)00009-8. [DOI] [PubMed] [Google Scholar]
  25. Kahn T., Savitsky M., Georgiev P. Attachment of HeT-A sequences to chromosomal termini in Drosophila melanogaster may occur by different mechanisms. Mol Cell Biol. 2000 Oct;20(20):7634–7642. doi: 10.1128/mcb.20.20.7634-7642.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kellum R., Raff J. W., Alberts B. M. Heterochromatin protein 1 distribution during development and during the cell cycle in Drosophila embryos. J Cell Sci. 1995 Apr;108(Pt 4):1407–1418. doi: 10.1242/jcs.108.4.1407. [DOI] [PubMed] [Google Scholar]
  27. Levis R. W., Ganesan R., Houtchens K., Tolar L. A., Sheen F. M. Transposons in place of telomeric repeats at a Drosophila telomere. Cell. 1993 Dec 17;75(6):1083–1093. doi: 10.1016/0092-8674(93)90318-k. [DOI] [PubMed] [Google Scholar]
  28. Lingner J., Hughes T. R., Shevchenko A., Mann M., Lundblad V., Cech T. R. Reverse transcriptase motifs in the catalytic subunit of telomerase. Science. 1997 Apr 25;276(5312):561–567. doi: 10.1126/science.276.5312.561. [DOI] [PubMed] [Google Scholar]
  29. Lis J. T., Simon J. A., Sutton C. A. New heat shock puffs and beta-galactosidase activity resulting from transformation of Drosophila with an hsp70-lacZ hybrid gene. Cell. 1983 Dec;35(2 Pt 1):403–410. doi: 10.1016/0092-8674(83)90173-3. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Löpez C. C., Nielsen L., Edström J. E. Terminal long tandem repeats in chromosomes form Chironomus pallidivittatus. Mol Cell Biol. 1996 Jul;16(7):3285–3290. doi: 10.1128/mcb.16.7.3285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Mason J. M., Biessmann H. The unusual telomeres of Drosophila. Trends Genet. 1995 Feb;11(2):58–62. doi: 10.1016/s0168-9525(00)88998-2. [DOI] [PubMed] [Google Scholar]
  33. Mason J. M., Strobel E., Green M. M. mu-2: mutator gene in Drosophila that potentiates the induction of terminal deficiencies. Proc Natl Acad Sci U S A. 1984 Oct;81(19):6090–6094. doi: 10.1073/pnas.81.19.6090. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. McEachern M. J., Hicks J. B. Unusually large telomeric repeats in the yeast Candida albicans. Mol Cell Biol. 1993 Jan;13(1):551–560. doi: 10.1128/mcb.13.1.551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Mikhailovsky S., Belenkaya T., Georgiev P. Broken chromosomal ends can be elongated by conversion in Drosophila melanogaster. Chromosoma. 1999 May;108(2):114–120. doi: 10.1007/s004120050358. [DOI] [PubMed] [Google Scholar]
  36. Nakamura T. M., Morin G. B., Chapman K. B., Weinrich S. L., Andrews W. H., Lingner J., Harley C. B., Cech T. R. Telomerase catalytic subunit homologs from fission yeast and human. Science. 1997 Aug 15;277(5328):955–959. doi: 10.1126/science.277.5328.955. [DOI] [PubMed] [Google Scholar]
  37. Pimpinelli S., Berloco M., Fanti L., Dimitri P., Bonaccorsi S., Marchetti E., Caizzi R., Caggese C., Gatti M. Transposable elements are stable structural components of Drosophila melanogaster heterochromatin. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3804–3808. doi: 10.1073/pnas.92.9.3804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Roth C. W., Kobeski F., Walter M. F., Biessmann H. Chromosome end elongation by recombination in the mosquito Anopheles gambiae. Mol Cell Biol. 1997 Sep;17(9):5176–5183. doi: 10.1128/mcb.17.9.5176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Rubin G. M. Isolation of a telomeric DNA sequence from Drosophila melanogaster. Cold Spring Harb Symp Quant Biol. 1978;42(Pt 2):1041–1046. doi: 10.1101/sqb.1978.042.01.104. [DOI] [PubMed] [Google Scholar]
  40. Rudkin G. T. Non replicating DNA in Drosophila. Genetics. 1969;61(1 Suppl):227–238. [PubMed] [Google Scholar]
  41. Samper E., Goytisolo F. A., Slijepcevic P., van Buul P. P., Blasco M. A. Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO Rep. 2000 Sep;1(3):244–252. doi: 10.1093/embo-reports/kvd051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Slijepcevic P., Hande M. P., Bouffler S. D., Lansdorp P., Bryant P. E. Telomere length, chromatin structure and chromosome fusigenic potential. Chromosoma. 1997 Dec;106(7):413–421. doi: 10.1007/s004120050263. [DOI] [PubMed] [Google Scholar]
  43. Smogorzewska A., van Steensel B., Bianchi A., Oelmann S., Schaefer M. R., Schnapp G., de Lange T. Control of human telomere length by TRF1 and TRF2. Mol Cell Biol. 2000 Mar;20(5):1659–1668. doi: 10.1128/mcb.20.5.1659-1668.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Teng S. C., Zakian V. A. Telomere-telomere recombination is an efficient bypass pathway for telomere maintenance in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Dec;19(12):8083–8093. doi: 10.1128/mcb.19.12.8083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Traverse K. L., Pardue M. L. Studies of He-T DNA sequences in the pericentric regions of Drosophila chromosomes. Chromosoma. 1989 Jan;97(4):261–271. doi: 10.1007/BF00371965. [DOI] [PubMed] [Google Scholar]
  46. Yeager T. R., Neumann A. A., Englezou A., Huschtscha L. I., Noble J. R., Reddel R. R. Telomerase-negative immortalized human cells contain a novel type of promyelocytic leukemia (PML) body. Cancer Res. 1999 Sep 1;59(17):4175–4179. [PubMed] [Google Scholar]
  47. Young B. S., Pession A., Traverse K. L., French C., Pardue M. L. Telomere regions in Drosophila share complex DNA sequences with pericentric heterochromatin. Cell. 1983 Aug;34(1):85–94. doi: 10.1016/0092-8674(83)90138-1. [DOI] [PubMed] [Google Scholar]
  48. de Lange T. Activation of telomerase in a human tumor. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):2882–2885. doi: 10.1073/pnas.91.8.2882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. van Steensel B., de Lange T. Control of telomere length by the human telomeric protein TRF1. Nature. 1997 Feb 20;385(6618):740–743. doi: 10.1038/385740a0. [DOI] [PubMed] [Google Scholar]

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