Telomeric 3'-overhang length is associated with the size of telomeres.
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.
Rahman
Ruman
R
Department of Gene Function & Development, Roslin Institute, Roslin, Midlothian EH25 9PS, UK.
Forsyth
Nicholas R
NR
Cui
Wei
W
D000818:Animals; D002455:Cell Division; D016922:Cellular Senescence / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D012756:Sheep; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
D019098:Telomerase