Article ID Journal Published Year Pages File Type
1907218 Experimental Gerontology 2008 8 Pages PDF
Abstract

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.

Related Topics
Life Sciences Biochemistry, Genetics and Molecular Biology Ageing
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