Abstract
In this study we have analysed mouse telomeres by Pulsed Field Gel Electrophoresis (PFGE). A number of specific restriction fragments hybridising to a (TTA-GGG)4 probe in the size range 50-150kb can be detected. These fragments are devoid of sites for most restriction enzymes suggesting that they comprise simple repeats; we argue that most of these are likely to be (TTAGGG)n. Each discrete fragment corresponds to the telomere of an individual chromosome and segregates as a Mendelian character. However, new size variants are being generated in the germ line at very high rates such that inbred mice are heterozygous at all telomeres analysable. In addition we show that specific small (approximately 4-12kb) fragments can be cleaved within some terminal arrays by the restriction enzyme MnII which recognises 5'(N7)GAGG3'. Like the complete telomere-repeat arrays (TRA's) these fragments form new variants at high rates and possibly by the same process. We speculate on the mechanisms that may be involved.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allshire R. C., Dempster M., Hastie N. D. Human telomeres contain at least three types of G-rich repeat distributed non-randomly. Nucleic Acids Res. 1989 Jun 26;17(12):4611–4627. doi: 10.1093/nar/17.12.4611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Allshire R. C., Gosden J. R., Cross S. H., Cranston G., Rout D., Sugawara N., Szostak J. W., Fantes P. A., Hastie N. D. Telomeric repeat from T. thermophila cross hybridizes with human telomeres. Nature. 1988 Apr 14;332(6165):656–659. doi: 10.1038/332656a0. [DOI] [PubMed] [Google Scholar]
- Bernards A., Michels P. A., Lincke C. R., Borst P. Growth of chromosome ends in multiplying trypanosomes. Nature. 1983 Jun 16;303(5918):592–597. doi: 10.1038/303592a0. [DOI] [PubMed] [Google Scholar]
- Brown W. R., MacKinnon P. J., Villasanté A., Spurr N., Buckle V. J., Dobson M. J. Structure and polymorphism of human telomere-associated DNA. Cell. 1990 Oct 5;63(1):119–132. doi: 10.1016/0092-8674(90)90293-n. [DOI] [PubMed] [Google Scholar]
- Brown W. R. Molecular cloning of human telomeres in yeast. Nature. 1989 Apr 27;338(6218):774–776. doi: 10.1038/338774a0. [DOI] [PubMed] [Google Scholar]
- Church G. M., Gilbert W. Genomic sequencing. Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991–1995. doi: 10.1073/pnas.81.7.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cross S. H., Allshire R. C., McKay S. J., McGill N. I., Cooke H. J. Cloning of human telomeres by complementation in yeast. Nature. 1989 Apr 27;338(6218):771–774. doi: 10.1038/338771a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Greider C. W., Blackburn E. H. A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis. Nature. 1989 Jan 26;337(6205):331–337. doi: 10.1038/337331a0. [DOI] [PubMed] [Google Scholar]
- Greider C. W., Blackburn E. H. Identification of a specific telomere terminal transferase activity in Tetrahymena extracts. Cell. 1985 Dec;43(2 Pt 1):405–413. doi: 10.1016/0092-8674(85)90170-9. [DOI] [PubMed] [Google Scholar]
- Greider C. W., Blackburn E. H. The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity. Cell. 1987 Dec 24;51(6):887–898. doi: 10.1016/0092-8674(87)90576-9. [DOI] [PubMed] [Google Scholar]
- Harley C. B., Futcher A. B., Greider C. W. Telomeres shorten during ageing of human fibroblasts. Nature. 1990 May 31;345(6274):458–460. doi: 10.1038/345458a0. [DOI] [PubMed] [Google Scholar]
- Hastie N. D., Allshire R. C. Human telomeres: fusion and interstitial sites. Trends Genet. 1989 Oct;5(10):326–331. doi: 10.1016/0168-9525(89)90137-6. [DOI] [PubMed] [Google Scholar]
- Hastie N. D., Dempster M., Dunlop M. G., Thompson A. M., Green D. K., Allshire R. C. Telomere reduction in human colorectal carcinoma and with ageing. Nature. 1990 Aug 30;346(6287):866–868. doi: 10.1038/346866a0. [DOI] [PubMed] [Google Scholar]
- Henderson E., Hardin C. C., Walk S. K., Tinoco I., Jr, Blackburn E. H. Telomeric DNA oligonucleotides form novel intramolecular structures containing guanine-guanine base pairs. Cell. 1987 Dec 24;51(6):899–908. doi: 10.1016/0092-8674(87)90577-0. [DOI] [PubMed] [Google Scholar]
- Hill R. E., Shaw P. H., Barth R. K., Hastie N. D. A genetic locus closely linked to a protease inhibitor gene complex controls the level of multiple RNA transcripts. Mol Cell Biol. 1985 Aug;5(8):2114–2122. doi: 10.1128/mcb.5.8.2114. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelly R., Bulfield G., Collick A., Gibbs M., Jeffreys A. J. Characterization of a highly unstable mouse minisatellite locus: evidence for somatic mutation during early development. Genomics. 1989 Nov;5(4):844–856. doi: 10.1016/0888-7543(89)90126-2. [DOI] [PubMed] [Google Scholar]
- Larson D. D., Spangler E. A., Blackburn E. H. Dynamics of telomere length variation in Tetrahymena thermophila. Cell. 1987 Jul 31;50(3):477–483. doi: 10.1016/0092-8674(87)90501-0. [DOI] [PubMed] [Google Scholar]
- 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]
- Morin G. B. The human telomere terminal transferase enzyme is a ribonucleoprotein that synthesizes TTAGGG repeats. Cell. 1989 Nov 3;59(3):521–529. doi: 10.1016/0092-8674(89)90035-4. [DOI] [PubMed] [Google Scholar]
- Moyzis R. K., Buckingham J. M., Cram L. S., Dani M., Deaven L. L., Jones M. D., Meyne J., Ratliff R. L., Wu J. R. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc Natl Acad Sci U S A. 1988 Sep;85(18):6622–6626. doi: 10.1073/pnas.85.18.6622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pietras D. F., Bennett K. L., Siracusa L. D., Woodworth-Gutai M., Chapman V. M., Gross K. W., Kane-Haas C., Hastie N. D. Construction of a small Mus musculus repetitive DNA library: identification of a new satellite sequence in Mus musculus. Nucleic Acids Res. 1983 Oct 25;11(20):6965–6983. doi: 10.1093/nar/11.20.6965. [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]
- Sen D., Gilbert W. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 1988 Jul 28;334(6180):364–366. doi: 10.1038/334364a0. [DOI] [PubMed] [Google Scholar]
- Shippen-Lentz D., Blackburn E. H. Functional evidence for an RNA template in telomerase. Science. 1990 Feb 2;247(4942):546–552. doi: 10.1126/science.1689074. [DOI] [PubMed] [Google Scholar]
- Shippen-Lentz D., Blackburn E. H. Telomere terminal transferase activity from Euplotes crassus adds large numbers of TTTTGGGG repeats onto telomeric primers. Mol Cell Biol. 1989 Jun;9(6):2761–2764. doi: 10.1128/mcb.9.6.2761. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sundquist W. I., Klug A. Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops. Nature. 1989 Dec 14;342(6251):825–829. doi: 10.1038/342825a0. [DOI] [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]
- Williamson J. R., Raghuraman M. K., Cech T. R. Monovalent cation-induced structure of telomeric DNA: the G-quartet model. Cell. 1989 Dec 1;59(5):871–880. doi: 10.1016/0092-8674(89)90610-7. [DOI] [PubMed] [Google Scholar]
- Yu G. L., Bradley J. D., Attardi L. D., Blackburn E. H. In vivo alteration of telomere sequences and senescence caused by mutated Tetrahymena telomerase RNAs. Nature. 1990 Mar 8;344(6262):126–132. doi: 10.1038/344126a0. [DOI] [PubMed] [Google Scholar]
- Zahler A. M., Prescott D. M. Telomere terminal transferase activity in the hypotrichous ciliate Oxytricha nova and a model for replication of the ends of linear DNA molecules. Nucleic Acids Res. 1988 Jul 25;16(14B):6953–6972. doi: 10.1093/nar/16.14.6953. [DOI] [PMC free article] [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]
- de Lange T., Shiue L., Myers R. M., Cox D. R., Naylor S. L., Killery A. M., Varmus H. E. Structure and variability of human chromosome ends. Mol Cell Biol. 1990 Feb;10(2):518–527. doi: 10.1128/mcb.10.2.518. [DOI] [PMC free article] [PubMed] [Google Scholar]