Abstract
Telomere dysfunctions, rendered through replicative attrition of telomeric DNA or due to the inhibition of shelterin components, are recognized as DNA double-stranded breaks (DSBs) by the DNA damage repair (DDR) pathway. This leads to the activation of DNA damage checkpoint sensors, including the Mre11-Rad50-Nbs1 (MRN) complex, γ-H2AX and 53BP1, the ATM and ATR signal-transducing kinases and downstream effectors, including Chk1, Chk2, and p53. Robust DNA damage response signals at dysfunctional telomeres, achieved by the complete deletion of TRF2 or by expressing dominant negative mutant TPP1ΔRD, can be detected by their association with γ-H2AX and 53BP1 forming “telomere dysfunction induced foci (TIFs).” Induction of TIFs at telomeres provides an opportunity to quantify the extent of telomere dysfunction and monitor the signaling pathways.
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References
Palm, W., and de Lange, T. (2008). How shelterin protects mammalian telomeres. Annu Rev Genet. 42, 301– 334.
de Lange, T. (2009) How telomeres solve the end-protection problem. Science 326, 948– 952.
de Lange, T. (2005) Shelterin: the protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100 –2110
d’Adda di Fagagna, F., Reaper, P.M., Clay-Farrace, L., Fiegler, H., Carr, P., Von Zglinicki, T., Saretzki, G., Carter, NP., and Jackson, S.P. (2003) A DNA damage checkpoint response in telomere initiated senescence. Nature 426, 194 –198
Takai, H., Smogorzewska, A., and de Lange, T. (2003) DNA damage foci at dysfunctional telomeres. Curr Biol. 13, 1549 –1556.
Deng, Y., Guo, X., Ferguson, D.O., and Chang, S. (2009) Multiple roles for MRE11 at uncapped telomeres. Nature 460, 914 –918.
Xin, H., Liu, D., Wan, M., Safari, A., Kim, H., Sun, W., O’Connor, M.S., and Songyang, Z. (2007) TPP1 is a homologue of ciliate TEBP-beta and interacts with POT1 to recruit telomerase. Nature 445, 559– 562.
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Rai, R., Chang, S. (2011). Probing the Telomere Damage Response. In: Songyang, Z. (eds) Telomeres and Telomerase. Methods in Molecular Biology, vol 735. Humana Press. https://doi.org/10.1007/978-1-61779-092-8_14
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DOI: https://doi.org/10.1007/978-1-61779-092-8_14
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