Ku70 stimulates fusion of dysfunctional telomeres yet protects chromosome ends from homologous recombination

Nature Cell Biology

Volumn 8, Issue 8, 2006, Pages 885-890

  Celli, Giulia B ^a,b   Denchi, Eros Lazzerini ^a   de Lange, Titia ^a  

^a ROCKEFELLER UNIVERSITY   (United States)

^b NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DNA; KU ANTIGEN; POLYDEOXYRIBONUCLEOTIDE SYNTHASE; TELOMERE BINDING PROTEIN; TELOMERIC REPEAT BINDING FACTOR 2;

ANIMAL CELL; ARTICLE; CELL VIABILITY; CONTROLLED STUDY; DNA DAMAGE; DNA STRUCTURE; GENE REPRESSION; GENETIC SUSCEPTIBILITY; HOMOLOGOUS RECOMBINATION; MOUSE; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TELOMERE;

ANIMALS; ANTIGENS, NUCLEAR; CHROMOSOMES, MAMMALIAN; DNA LIGASES; DNA REPAIR; DNA-BINDING PROTEINS; IMMUNOBLOTTING; MICE; MICE, KNOCKOUT; MICROSCOPY, FLUORESCENCE; MODELS, BIOLOGICAL; PROTEIN-SERINE-THREONINE KINASES; RECOMBINATION, GENETIC; SIGNAL TRANSDUCTION; SISTER CHROMATID EXCHANGE; TELOMERE; TELOMERIC REPEAT BINDING PROTEIN 2;

MAMMALIA;

EID: 33746644257     PISSN: 14657392     EISSN: None     Source Type: Journal    
DOI: 10.1038/ncb1444     Document Type: Article

References (35)

1. Hsu, H. L., Gilley, D., Blackburn, E. H. & Chen, D. J. Ku is associated with the telomere in mammals. Proc. Natl Acad. Sci. USA 96, 12454-12458 (1999).
2. Hsu, H. L. et al. Ku acts in a unique way at the mammalian telomere to prevent end joining. Genes Dev. 14, 2807-2812 (2000).
3. Song, K., Jung, D., Jung, Y., Lee, S. G. & Lee, I. Interaction of human Ku70 with TRF2. FEBS Lett. 481, 81-85 (2000).
4. d'Adda di Fagagna, F. et al. Effects of DNA nonhomologous end-joining factors on telomere length and chromosomal stability in mammalian cells. Curr. Biol. 11, 1192-1196 (2001).
5. Gilley, D. et al. DNA-PKcs is critical for telomere capping. Proc. Natl Acad. Sci. USA 98, 15084-15088 (2001).
6. O'Connor, M. S., Safari, A., Liu, D., Qin, J. & Songyang, Z. The human Rap1 protein complex and modulation of telomere length. J. Biol. Chem. 279, 28585-28591 (2004).
7. Gu, Y. et al. Growth retardation and leaky SCID phenotype of Ku70-deficient mice. Immunity 7, 653-665 (1997).
8. Dunham, M. A., Neumann, A. A., Fasching, C. L. & Reddel, R. R. Telomere maintenance by recombination in human cells. Nature Genet. 26, 447-450 (2000).
9. de Lange, T. Shelterin: The protein complex that shapes and safeguards human telomeres. Genes Dev. 19, 2100-2110 (2005).
10. Celli, G. & de Lange, T. DNA processing not required for ATM-mediated telomere damage response after TRF2 deletion. Nature Cell Biol. 7, 712-718 (2005).
11. Smogorzewska, A. & de Lange, T. Different telomere damage signaling pathways in human and mouse cells. EMBO J. 21, 4338-4348 (2002).
12. Ma, J. L., Kim, E. M., Haber, J. E. & Lee, S. E. Yeast Mre11 and Rad1 proteins define a Ku-independent mechanism to repair double-strand breaks lacking overlapping end sequences. Mol. Cell. Biol. 23, 8820-8828 (2003).
13. Walker, J. R., Corpina, R. A. & Goldberg, J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature 412, 607-614 (2001).
14. Griffith, J. D. et al. Mammalian telomeres end in a large duplex loop. Cell 97, 503-514 (1999).
15. Stansel, R. M., de Lange, T. & Griffith, J. D. T-loop assembly in vitro involves binding of TRF2 near the 3′ telomeric overhang. EMBO J. 20, 5532-5540 (2001).
16. Bertuch, A. A. & Lundblad, V. Which end: Dissecting Ku's function at telomeres and double-strand breaks. Genes Dev. 17, 2347-2350 (2003).
17. Riha, K., Watson, J. M., Parkey, J. & Shippen, D. E. Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70. EMBO J. 21, 2819-2826 (2002).
18. Espejel, S. et al. Mammalian Ku86 mediates chromosomal fusions and apoptosis caused by critically short telomeres. EMBO J. 21, 2207-2219 (2002).
19. Samper, E., Goytisolo, F. A., Slijepcevic, P., van Buul, P. P. & Blasco, M. A. Mammalian Ku86 protein prevents telomeric fusions independently of the length of TTAGGG repeats and the G-strand overhang. EMBO Rep. 1, 244-252 (2000).
20. d'Adda di Fagagna, F. et al. A DNA damage checkpoint response in telomere-initiated senescence. Nature 426, 194-198 (2003).
21. Takai, H., Smogorzewska, A. & de Lange, T. DNA damage foci at dysfunctional telomeres. Curr. Biol. 13, 1549-1556 (2003).
22. Bailey, S. M., Brenneman, M. A. & Goodwin, E. H. Frequent recombination in telomeric DNA may extend the proliferative life of telomerase-negative cells. Nucleic Acids Res. 32, 3743-3751 (2004).
23. Bechter, O. E., Zou, Y., Walker, W., Wright, W. E. & Shay, J. W. Telomeric recombination in mismatch repair deficient human colon cancer cells after telomerase inhibition. Cancer Res. 64, 3444-3451 (2004).
24. Bailey, S. M., Cornforth, M. N., Kurimasa, A., Chen, D. J. & Goodwin, E. H. Strand-specific postreplicative processing of mammalian telomeres. Science 293, 2462-2465 (2001).
25. Wang, Y. et al. An increase in telomere sister chromatid exchange in murine embryonic stem cells possessing critically shortened telomeres. Proc. Natl Acad. Sci. USA 102, 10256-10260 (2005).
26. Laud, P. R. et al. Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes Dev. 19, 2560-2570 (2005).
27. Wang, R. C., Smogorzewska, A. & de Lange, T. Homologous recombination generates T-loop-sized deletions at human telomeres. Cell 119, 355-368 (2004).
28. Pierce, A. J., Hu, P., Han, M., Ellis, N. & Jasin, M. Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells. Genes Dev. 15, 3237-3242 (2001).
29. Weinstock, D. M. & Jasin, M. Alternative pathways for the repair of RAG-induced DNA breaks. Mol. Cell. Biol. 26, 131-139 (2006).
30. Adachi, N., Ishino, T., Ishii, Y., Takeda, S. & Koyama, H. DNA ligase IV-deficient cells are more resistant to ionizing radiation in the absence of Ku70: Implications for DNA double-strand break repair. Proc. Natl Acad. Sci. USA 98, 12109-12113 (2001).
31. DuBois, M. L., Haimberger, Z. W., McIntosh, M. W. & Gottschling, D. E. A quantitative assay for telomere protection in Saccharomyces cerevisiae. Genetics 161, 995-1013 (2002).
32. Polotnianka, R. M., Li, J. & Lustig, A. J. The yeast Ku heterodimer is essential for protection of the telomere against nucleolytic and recombinational activities. Curr. Biol. 8, 831-834 (1998).
33. Baumann, P. & Cech, T. R. Protection of telomeres by the Ku protein in fission yeast. Mol. Biol. Cell 11, 3265-3275 (2000).
34. Bianchi, A. & de Lange, T. Ku binds telomeric DNA in vitro. J. Biol. Chem. 274, 21223-21227 (1999).
35. Li, G., Nelsen, C. & Hendrickson, E. A. Ku86 is essential in human somatic cells. Proc. Natl Acad. Sci. USA 99, 832-837 (2002).