Telomeric DNA damage is irreparable and causes persistent DNA-damage-response activation (original) (raw)

• Campisi, J. & d’Adda di Fagagna, F. Cellular senescence: when bad things happen to good cells. Nat. Rev. Mol. Cell Biol. 8, 729–740 (2007).
  Article CAS Google Scholar
• Collado, M., Blasco, M. A. & Serrano, M. Cellular senescence in cancer and aging. Cell 130, 223–233 (2007).
  Article CAS Google Scholar
• Braig, M. et al. Oncogene-induced senescence as an initial barrier in lymphoma development. Nature 436, 660–665 (2005).
  Article CAS Google Scholar
• Chen, Z. et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 436, 725–730 (2005).
  Article CAS Google Scholar
• Collado, M. et al. Tumour biology: senescence in premalignant tumours. Nature 436, 642 (2005).
  Article CAS Google Scholar
• Michaloglou, C. et al. BRAFE600-associated senescence-like cell cycle arrest of human naevi. Nature 436, 720–724 (2005).
  Article CAS Google Scholar
• Baker, D. J. et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 479, 232–236 (2011).
  Article CAS Google Scholar
• d’Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194–198 (2003).
  Article Google Scholar
• Herbig, U., Jobling, W. A., Chen, B. P., Chen, D. J. & Sedivy, J. M. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol. Cell 14, 501–513 (2004).
  Article CAS Google Scholar
• Harley, C. B., Futcher, A. B. & Greider, C. W. Telomeres shorten during ageing of human fibroblasts. Nature 345, 458–460 (1990).
  Article CAS Google Scholar
• Evan, G. I. & d’Adda di Fagagna, F. Cellular senescence: hot or what? Curr. Opin. Genet. Dev. 19, 25–31 (2009).
  Article CAS Google Scholar
• Halazonetis, T. D., Gorgoulis, V. G. & Bartek, J. An oncogene-induced DNA damage model for cancer development. Science 319, 1352–1355 (2008).
  Article CAS Google Scholar
• Schmitt, C. A. Senescence, apoptosis and therapy-cutting the lifelines of cancer. Nat. Rev. Cancer 3, 286–295 (2003).
  Article CAS Google Scholar
• Herbig, U., Ferreira, M., Condel, L., Carey, D. & Sedivy, J. M. Cellular senescence in aging primates. Science 311, 1257 (2006).
  Article CAS Google Scholar
• Rossi, D. J. et al. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age. Nature 447, 725–729 (2007).
  Article CAS Google Scholar
• Nijnik, A. et al. DNA repair is limiting for haematopoietic stem cells during ageing. Nature 447, 686–690 (2007).
  Article CAS Google Scholar
• Jeyapalan, J. C., Ferreira, M., Sedivy, J. M. & Herbig, U. Accumulation of senescent cells in mitotic tissue of aging primates. Mech. Ageing Dev. 128, 36–44 (2007).
  Article CAS Google Scholar
• Jackson, S. P. & Bartek, J. The DNA-damage response in human biology and disease. Nature 461, 1071–1078 (2009).
  Article CAS Google Scholar
• Meier, A. et al. Spreading of mammalian DNA-damage response factors studied by ChIP-chip at damaged telomeres. EMBO J. 26, 2707–2718 (2007).
  Article CAS Google Scholar
• Zhou, B. B. & Bartek, J. Targeting the checkpoint kinases: chemosensitization versus chemoprotection. Nat. Rev. Cancer 4, 216–225 (2004).
  Article CAS Google Scholar
• Rodier, F. et al. DNA-SCARS: distinct nuclear structures that sustain damage-induced senescence growth arrest and inflammatory cytokine secretion. J. Cell Sci. 124, 68–81 (2011).
  Article CAS Google Scholar
• O’Sullivan, R. J. & Karlseder, J. Telomeres: protecting chromosomes against genome instability. Nat. Rev. Mol. Cell Biol. 11, 171–181 (2010).
  Article Google Scholar
• Bae, N. S. & Baumann, P. A RAP1/TRF2 complex inhibits nonhomologous end-joining at human telomeric DNA ends. Mol. Cell 26, 323–334 (2007).
  Article CAS Google Scholar
• Bombarde, O. et al. TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends. EMBO J. 29, 1573–1584 (2010).
  Article CAS Google Scholar
• Hewitt, G. et al. Telomeres are favoured targets of a persistent DNA damage response in ageing and stress-induced senescence. Nat. Commun. 3, 708 (2012).
  Article Google Scholar
• Le, O. N. et al. Ionizing radiation-induced long-term expression of senescence markers in mice is independent of p53 and immune status. Aging Cell 9, 398–409 (2010).
  Article CAS Google Scholar
• Van Steensel, B., Smogorzewska, A. & de Lange, T. TRF2 protects human telomeres from end-to-end fusions. Cell 92, 401–413 (1998).
  Article CAS Google Scholar
• Takai, H., Smogorzewska, A. & de Lange, T. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13, 1549–1556 (2003).
  Article CAS Google Scholar
• Fujita, K. et al. Positive feedback between p53 and TRF2 during telomere-damage signalling and cellular senescence. Nat. Cell Biol. 12, 1205–1212 (2010).
  Article CAS Google Scholar
• Gonzalo, S. et al. Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat. Cell Biol. 7, 420–428 (2005).
  Article CAS Google Scholar
• Marchion, D. C., Bicaku, E., Daud, A. I., Sullivan, D. M. & Munster, P. N. Valproic acid alters chromatin structure by regulation of chromatin modulation proteins. Cancer Res. 65, 3815–3822 (2005).
  Article CAS Google Scholar
• Goodarzi, A. A. et al. ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol. Cell 31, 167–177 (2008).
  Article CAS Google Scholar
• Diede, S. J. & Gottschling, D. E. Exonuclease activity is required for sequence addition and Cdc13p loading at a de novo telomere. Curr. Biol. 11, 1336–1340 (2001).
  Article CAS Google Scholar
• Michelson, R. J., Rosenstein, S. & Weinert, T. A telomeric repeat sequence adjacent to a DNA double-stranded break produces an anticheckpoint. Genes Dev. 19, 2546–2559 (2005).
  Article CAS Google Scholar
• Marcand, S., Pardo, B., Gratias, A., Cahun, S. & Callebaut, I. Multiple pathways inhibit NHEJ at tolemeres. Genes Dev. 22, 1153–1158 (2008).
  Article CAS Google Scholar
• Celli, G. B. & de Lange, T. DNA processing is not required for ATM-mediated telomere damage response after TRF2 deletion. Nat. Cell Biol. 7, 712–718 (2005).
  Article CAS Google Scholar
• Ancelin, K. et al. Targeting assay to study the cis functions of human telomeric proteins: evidence for inhibition of telomerase by TRF1 and for activation of telomere degradation by TRF2. Mol. Cell Biol. 22, 3474–3487 (2002).
  Article CAS Google Scholar
• Soutoglou, E. et al. Positional stability of single double-strand breaks in mammalian cells. Nat. Cell Biol. 9, 675–682 (2007).
  Article CAS Google Scholar
• Huang, L. C., Clarkin, K. C. & Wahl, G. M. Sensitivity and selectivity of the DNA damage sensor responsible for activating p53-dependent G1 arrest. Proc. Natl Acad. Sci. USA 93, 4827–4832 (1996).
  Article CAS Google Scholar
• Petersen, S., Saretzki, G. & von Zglinicki, T. Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. Exp. Cell Res. 239, 152–160 (1998).
  Article CAS Google Scholar
• Rochette, P. J. & Brash, D. E. Human telomeres are hypersensitive to UV-induced DNA damage and refractory to repair. PLoS Genet. 6, e1000926 (2010).
  Article Google Scholar
• Gomes, N. M. et al. Comparative biology of mammalian telomeres: hypotheses on ancestral states and the roles of telomeres in longevity determination. Aging Cell 10, 761–768 (2011).
  Article CAS Google Scholar
• Giaimo, S. & d’Adda di Fagagna, F. Is cellular senescence an example of antagonistic pleiotropy? Aging Celldoi: 10.1111/j.1474-9726.2012.00807.x (2012).
• Marusyk, A., Wheeler, L. J., Mathews, C. K. & DeGregori, J. p53 mediates senescence-like arrest induced by chronic replicational stress. Mol. Cell Biol. 27, 5336–5351 (2007).
  Article CAS Google Scholar
• Di Micco, R. et al. Oncogene-induced senescence is a DNA damage response triggered by DNA hyper-replication. Nature 444, 638–642 (2006).
  Article CAS Google Scholar
• Ye, J. et al. TRF2 and apollo cooperate with topoisomerase 2_α_ to protect human telomeres from replicative damage. Cell 142, 230–242 (2010).
  Article CAS Google Scholar
• Soutoglou, E. & Misteli, T. Activation of the cellular DNA damage response in the absence of DNA lesions. Science 320, 1507–1510 (2008).
  Article CAS Google Scholar
• Ziv, Y. et al. Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat. Cell Biol. 8, 870–876 (2006).
  Article CAS Google Scholar
• Francia, S., Weiss, R. S. & d’Adda di Fagagna, F. Need telomere maintenance? Call 911 Cell Div. 2, 3 (2007).
  Article Google Scholar
• Ghisletti, S. et al. Identification and characterization of enhancers controlling the inflammatory gene expression program in macrophages. Immunity 32, 317–328 (2010).
  Article CAS Google Scholar
• Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics 26, 589–595 (2010).
  Article Google Scholar
• Nobuyuki, O. A threshold selection method from gray-level histograms. IEEE Trans. Sys. Man. Cyber. 9, 62–66 (1979).
  Article Google Scholar
• Duffy, D. L. Lodplot: plot a genome scan. R package version 1.1. (2007).
• The R Development Core Team, R: A Language and Environment for Statistical Computing (R Foundation for Statistical Computing, Vienna, Austria, 2008.
• Di Micco, R. et al. Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nat. Cell Biol. 13, 292–302 (2011).
  Article CAS Google Scholar
• Viscardi, V., Bonetti, D., Cartagena-Lirola, H., Lucchini, G. & Longhese, M. P. MRX-dependent DNA damage response to short telomeres. Mol. Biol. Cell 18, 3047–3058 (2007).
  Article CAS Google Scholar