Structure and variability of human chromosome ends.
Open accessAbstract
Mammalian telomeres are thought to be composed of a tandem array of TTAGGG repeats. To further define the type and arrangement of sequences at the ends of human chromosomes, we developed a direct cloning strategy for telomere-associated DNA. The method involves a telomere enrichment procedure based on the relative lack of restriction endonuclease cutting sites near the ends of human chromosomes. Nineteen (TTAGGG)n-bearing plasmids were isolated, two of which contain additional human sequences proximal to the telomeric repeats. These telomere-flanking sequences detect BAL 31-sensitive loci and thus are located close to chromosome ends. One of the flanking regions is part of a subtelomeric repeat that is present at 10 to 25% of the chromosome ends in the human genome. This sequence is not conserved in rodent DNA and therefore should be a helpful tool for physical characterization of human chromosomes in human-rodent hybrid cell lines; some of the chromosomes that may be analyzed in this manner have been identified, i.e., 7, 16, 17, and 21. The minimal size of the subtelomeric repeat is 4 kilobases (kb); it shows a high frequency of restriction fragment length polymorphisms and undergoes extensive de novo methylation in somatic cells. Distal to the subtelomeric repeat, the chromosomes terminate in a long region (up to 14 kb) that may be entirely composed of TTAGGG repeats. This terminal segment is unusually variable. Although sperm telomeres are 10 to 14 kb long, telomeres in somatic cells are several kilobase pairs shorter and very heterogeneous in length. Additional telomere reduction occurs in primary tumors, indicating that somatic telomeres are unstable and may continuously lose sequences from their termini.
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Telomeres in human cancer are often shorter than in normal tissues.
“Telomeres in human cancer are often shorter than in normal tissues135.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [135]
Shorter telomeres are frequently observed in cancer relative to adjacent normal tissue.
“Shorter telomeres are frequently observed in cancer relative to their adjacent normal tissue135–142.”
From Telomeres in cancer: tumour suppression and genome instability (2017) · cites this paper as [135]
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- Authors
- de Lange, T., Shiue, L., Myers, R. M., Cox, D. R., Naylor, S. L., Killery, A. M., & Varmus, H. E.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 1990-02
- Volume
- 10
- Issue
- 2
- Pages
- 518-527
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC360828
- OpenAlex
- W1852455217
- Cited by
- 848
- References
- 46
- Citations by year
- 2026: 5 · 2025: 5 · 2024: 15 · 2023: 15 · 2022: 11 · 2021: 21 · 2020: 17 · 2019: 19 · 2018: 14 · 2017: 16 · 2016: 18 · 2015: 13 · 2014: 22 · 2013: 33 · 2012: 26
- FWCI
- 19.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- telomeres, human chromosomes, TTAGGG repeats, subtelomeric repeats, restriction fragment length polymorphism
- MeSH terms
- Animals, Base Sequence, Cell Line, Chromosome Mapping, Chromosomes, Human, DNA, DNA, Recombinant, HeLa Cells, Humans, Hybrid Cells, Male, Molecular Sequence Data, Plasmids, Semen, Spermatozoa, Blotting, Southern, Restriction Mapping, Gene Library
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