Telomere shortening during replicative exhaustion

Stable Identifier
R-HSA-3785711
Type
Reaction [BlackBoxEvent]
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

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
10669743 Control of human telomere length by TRF1 and TRF2

Smogorzewska, A, van Steensel, B, Bianchi, A, Oelmann, S, Schaefer, MR, Schnapp, G, de Lange, T

Mol. Cell. Biol. 2000
16166375 Shelterin: the protein complex that shapes and safeguards human telomeres

de Lange, T

Genes Dev 2005
2342578 Telomeres shorten during ageing of human fibroblasts

Harley, CB, Futcher, AB, Greider, CW

Nature 1990
2392154 Telomere reduction in human colorectal carcinoma and with ageing

Hastie, ND, Dempster, M, Dunlop, MG, Thompson, AM, Green, DK, Allshire, RC

Nature 1990
Participants
Participant Of
Orthologous Events
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Reviewed