期刊
EXPERIMENTAL GERONTOLOGY
卷 43, 期 4, 页码 258-265出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2008.01.005
关键词
telomere; telomerase; telomeric T-overhang; senescence; hTERT-immortalized
资金
- Biotechnology and Biological Sciences Research Council Funding Source: Medline
Telomeres are specialized DNA/protein complexes that cap eukaryotic chromosome ends as T-loop structures and maintain genomic integrity. Vertebrate telomeric DNA consists of tandem double-strand repeats which terminate in a 3' single-strand G-rich overhang. The telomeric 3'-overhang is important for the formation of the T-loop. In mammalian mortal somatic cells, telomeres shorten with each successive division and contribute to the onset of replicative senescence. The exact molecular mechanism underlying replicative senescence remains unclear: whether telomere shortening is the only trigger or loss of telomeric 3'-overhang plays a causal role. To further address this issue, we investigated telomeric 3'-overhang and telomere changes during cell proliferation toward replicative senescence. We demonstrate here that telomeric 3'-overhang, similar to telomeres, exhibits progressive attrition with each cell division in primary sheep fibroblasts and that telomeric 3'-overhang size does not determine the rate of telomere shortening. Furthermore, the sizes of telomeric 3'-overhangs are associated with telomere lengths. Our results suggest that alteration of the 3'-overhang and the telomere during cellular proliferation are associated. Together they may contribute to maintain chromosomal stability and to regulate replicative senescence. (C) 2008 Elsevier Inc. All rights reserved.
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