Reactome | Telomere shortening during replicative exhaustion

Telomere shortening during replicative exhaustion

Stable Identifier

R-HSA-3785711

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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Telomere shortening during replicative exhaustion

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In somatic cells where telomerase is not active, telomeric DNA shortens with each cell division (Harley et al. 1990, Hastie et al. 1990). This may be especially pronounced in cells undergoing replicative exhaustion due to oncogenic signaling-driven cell division. The shelterin complex, which protects telomeres from being recognized as double strand DNA breaks (reviewed by de Lange 2005), binds telomeric DNA through interaction of its subunits TREF1 (TRF1) and TREF2 (TRF2) with long TTAGGG repeat tracts (Smogorzewska et al. 2000). Telomere shortening due to replicative exhaustion results in a decreased number of TTAGGG repeats, which negatively impacts shelterin binding to telomeric DNA.

Literature References

PubMed ID	Title	Journal	Year
16166375	Shelterin: the protein complex that shapes and safeguards human telomeres de Lange, T	Genes Dev	2005
10669743	Control of human telomere length by TRF1 and TRF2 van Steensel, B, Schnapp, G, Schaefer, MR, Oelmann, S, Smogorzewska, A, de Lange, T, Bianchi, A	Mol. Cell. Biol.	2000
2342578	Telomeres shorten during ageing of human fibroblasts Greider, CW, Futcher, AB, Harley, CB	Nature	1990
2392154	Telomere reduction in human colorectal carcinoma and with ageing Dempster, M, Thompson, AM, Dunlop, MG, Allshire, RC, Green, DK, Hastie, ND	Nature	1990