Abstract
One of the functions of telomeres is to counteract the terminal nucleotide loss associated with DNA replication. While the vast majority of eukaryotic organisms maintain their chromosome ends via telomerase, an enzyme system that generates short, tandem repeats on the ends of chromosomes, other mechanisms such as the transposition of retrotransposons or recombination can also be used in some species. Chromosome end regression and extension were studied in a medically important mosquito, the malaria vector Anopheles gambiae, to determine how this dipteran insect maintains its chromosome ends. The insertion of a transgenic pUChsneo plasmid at the left end of chromosome 2 provided a unique marker for measuring the dynamics of the 2L telomere over a period of about 3 years. The terminal length was relatively uniform in the 1993 population with the chromosomes ending within the white gene sequence of the inserted transgene. Cloned terminal chromosome fragments did not end in short repeat sequences that could have been synthesized by telomerase. By late 1995, the chromosome ends had become heterogeneous: some had further shortened while other chromosomes had been elongated by regenerating part of the integrated pUChsneo plasmid. A model is presented for extension of the 2L chromosome by recombination between homologous 2L chromosome ends by using the partial plasmid duplication generated during its original integration. It is postulated that this mechanism is also important in wild-type telomere elongation.
Full Text
The Full Text of this article is available as a PDF (1.2 MB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Biessmann H., Carter S. B., Mason J. M. Chromosome ends in Drosophila without telomeric DNA sequences. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1758–1761. doi: 10.1073/pnas.87.5.1758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Biessmann H., Donath J., Walter M. F. Molecular characterization of the Anopheles gambiae 2L telomeric region via an integrated transgene. Insect Mol Biol. 1996 Feb;5(1):11–20. doi: 10.1111/j.1365-2583.1996.tb00035.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Biessmann H., Mason J. M. Genetics and molecular biology of telomeres. Adv Genet. 1992;30:185–249. doi: 10.1016/s0065-2660(08)60321-1. [DOI] [PubMed] [Google Scholar]
- Biessmann H., Mason J. M. Progressive loss of DNA sequences from terminal chromosome deficiencies in Drosophila melanogaster. EMBO J. 1988 Apr;7(4):1081–1086. doi: 10.1002/j.1460-2075.1988.tb02916.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Biessmann H., Valgeirsdottir K., Lofsky A., Chin C., Ginther B., Levis R. W., Pardue M. L. HeT-A, a transposable element specifically involved in "healing" broken chromosome ends in Drosophila melanogaster. Mol Cell Biol. 1992 Sep;12(9):3910–3918. doi: 10.1128/mcb.12.9.3910. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Cohn M., Edström J. E. Telomere-associated repeats in Chironomus form discrete subfamilies generated by gene conversion. J Mol Evol. 1992 Aug;35(2):114–122. doi: 10.1007/BF00183222. [DOI] [PubMed] [Google Scholar]
- Dancis B. M., Holmquist G. P. Telomere replication and fusion in eukaryotes. J Theor Biol. 1979 May 21;78(2):211–224. doi: 10.1016/0022-5193(79)90265-0. [DOI] [PubMed] [Google Scholar]
- Graziosi C., Sakai R. K., Romans P., Miller L. H., Wellems T. E. Method for in situ hybridization to polytene chromosomes from ovarian nurse cells of Anopheles gambiae (Diptera: Culicidae). J Med Entomol. 1990 Sep;27(5):905–912. doi: 10.1093/jmedent/27.5.905. [DOI] [PubMed] [Google Scholar]
- Greider C. W. Telomere length regulation. Annu Rev Biochem. 1996;65:337–365. doi: 10.1146/annurev.bi.65.070196.002005. [DOI] [PubMed] [Google Scholar]
- Kramer K. M., Haber J. E. New telomeres in yeast are initiated with a highly selected subset of TG1-3 repeats. Genes Dev. 1993 Dec;7(12A):2345–2356. doi: 10.1101/gad.7.12a.2345. [DOI] [PubMed] [Google Scholar]
- Lamb J., Harris P. C., Wilkie A. O., Wood W. G., Dauwerse J. G., Higgs D. R. De novo truncation of chromosome 16p and healing with (TTAGGG)n in the alpha-thalassemia/mental retardation syndrome (ATR-16). Am J Hum Genet. 1993 Apr;52(4):668–676. [PMC free article] [PubMed] [Google Scholar]
- Levis R. W. Drosophila melanogaster does not share the telomeric repeat sequence of another invertebrate, Ascaris lumbricoides. Mol Gen Genet. 1993 Jan;236(2-3):440–442. doi: 10.1007/BF00277145. [DOI] [PubMed] [Google Scholar]
- Levis R. W. Viable deletions of a telomere from a Drosophila chromosome. Cell. 1989 Aug 25;58(4):791–801. doi: 10.1016/0092-8674(89)90112-8. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Marck C. 'DNA Strider': a 'C' program for the fast analysis of DNA and protein sequences on the Apple Macintosh family of computers. Nucleic Acids Res. 1988 Mar 11;16(5):1829–1836. doi: 10.1093/nar/16.5.1829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- McEachern M. J., Blackburn E. H. Cap-prevented recombination between terminal telomeric repeat arrays (telomere CPR) maintains telomeres in Kluyveromyces lactis lacking telomerase. Genes Dev. 1996 Jul 15;10(14):1822–1834. doi: 10.1101/gad.10.14.1822. [DOI] [PubMed] [Google Scholar]
- Meyne J., Ratliff R. L., Moyzis R. K. Conservation of the human telomere sequence (TTAGGG)n among vertebrates. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7049–7053. doi: 10.1073/pnas.86.18.7049. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller L. H., Sakai R. K., Romans P., Gwadz R. W., Kantoff P., Coon H. G. Stable integration and expression of a bacterial gene in the mosquito Anopheles gambiae. Science. 1987 Aug 14;237(4816):779–781. doi: 10.1126/science.3039658. [DOI] [PubMed] [Google Scholar]
- Mimori T., Hardin J. A., Steitz J. A. Characterization of the DNA-binding protein antigen Ku recognized by autoantibodies from patients with rheumatic disorders. J Biol Chem. 1986 Feb 15;261(5):2274–2278. [PubMed] [Google Scholar]
- Murnane J. P., Sabatier L., Marder B. A., Morgan W. F. Telomere dynamics in an immortal human cell line. EMBO J. 1994 Oct 17;13(20):4953–4962. doi: 10.1002/j.1460-2075.1994.tb06822.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Müller F., Wicky C., Spicher A., Tobler H. New telomere formation after developmentally regulated chromosomal breakage during the process of chromatin diminution in Ascaris lumbricoides. Cell. 1991 Nov 15;67(4):815–822. doi: 10.1016/0092-8674(91)90076-b. [DOI] [PubMed] [Google Scholar]
- Okazaki S., Tsuchida K., Maekawa H., Ishikawa H., Fujiwara H. Identification of a pentanucleotide telomeric sequence, (TTAGG)n, in the silkworm Bombyx mori and in other insects. Mol Cell Biol. 1993 Mar;13(3):1424–1432. doi: 10.1128/mcb.13.3.1424. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Richards E. J., Ausubel F. M. Isolation of a higher eukaryotic telomere from Arabidopsis thaliana. Cell. 1988 Apr 8;53(1):127–136. doi: 10.1016/0092-8674(88)90494-1. [DOI] [PubMed] [Google Scholar]
- Rogan E. M., Bryan T. M., Hukku B., Maclean K., Chang A. C., Moy E. L., Englezou A., Warneford S. G., Dalla-Pozza L., Reddel R. R. Alterations in p53 and p16INK4 expression and telomere length during spontaneous immortalization of Li-Fraumeni syndrome fibroblasts. Mol Cell Biol. 1995 Sep;15(9):4745–4753. doi: 10.1128/mcb.15.9.4745. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scherf A., Mattei D. Cloning and characterization of chromosome breakpoints of Plasmodium falciparum: breakage and new telomere formation occurs frequently and randomly in subtelomeric genes. Nucleic Acids Res. 1992 Apr 11;20(7):1491–1496. doi: 10.1093/nar/20.7.1491. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sheen F. M., Levis R. W. Transposition of the LINE-like retrotransposon TART to Drosophila chromosome termini. Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12510–12514. doi: 10.1073/pnas.91.26.12510. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Steller H., Pirrotta V. A transposable P vector that confers selectable G418 resistance to Drosophila larvae. EMBO J. 1985 Jan;4(1):167–171. doi: 10.1002/j.1460-2075.1985.tb02332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strahl C., Blackburn E. H. Effects of reverse transcriptase inhibitors on telomere length and telomerase activity in two immortalized human cell lines. Mol Cell Biol. 1996 Jan;16(1):53–65. doi: 10.1128/mcb.16.1.53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Traverse K. L., Pardue M. L. A spontaneously opened ring chromosome of Drosophila melanogaster has acquired He-T DNA sequences at both new telomeres. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8116–8120. doi: 10.1073/pnas.85.21.8116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wang S. S., Zakian V. A. Telomere-telomere recombination provides an express pathway for telomere acquisition. Nature. 1990 May 31;345(6274):456–458. doi: 10.1038/345456a0. [DOI] [PubMed] [Google Scholar]
- Wilkie A. O., Lamb J., Harris P. C., Finney R. D., Higgs D. R. A truncated human chromosome 16 associated with alpha thalassaemia is stabilized by addition of telomeric repeat (TTAGGG)n. Nature. 1990 Aug 30;346(6287):868–871. doi: 10.1038/346868a0. [DOI] [PubMed] [Google Scholar]
- Yu G. L., Blackburn E. H. Developmentally programmed healing of chromosomes by telomerase in Tetrahymena. Cell. 1991 Nov 15;67(4):823–832. doi: 10.1016/0092-8674(91)90077-c. [DOI] [PubMed] [Google Scholar]
- 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]
- Zhang Y. J., Kamnert I., López C. C., Cohn M., Edström J. E. A family of complex tandem DNA repeats in the telomeres of Chironomus pallidivittatus. Mol Cell Biol. 1994 Dec;14(12):8028–8036. doi: 10.1128/mcb.14.12.8028. [DOI] [PMC free article] [PubMed] [Google Scholar]
