Nucleic Acids Research, Vol 24, Issue 23 4639-4648, Copyright © 1996 by Oxford University Press
SJ Boulton and SP Jackson
Ku is a heterodimer of polypeptides of approximately 70 and 80 kDa (Ku70
and Ku80, respectively) that binds to DNA ends. Mammalian cells lacking Ku
are defective in DNA double-strand break (DSB) repair and in site-specific
V(D)J recombination. Here, we describe the identification and
characterisation of YKU80, the gene for the Saccharomyces cerevisiae Ku80
homologue. Significantly, we find that YKU80 disruption enhances the
radiosensitivity of rad52 mutant strains, suggesting that YKU80 functions
in a DNA DSB repair pathway that does not rely on homologous recombination.
Indeed, through using an in vivo plasmid rejoining assay, we find that
YKU80 plays an essential role in illegitimate recombination events that
result in the accurate repair of restriction enzyme generated DSBs.
Interestingly, in the absence of YKU80function, residual repair operates
through an error-prone pathway that results in recombination between short
direct repeat elements. This resembles closely a predominant DSB repair
pathway in vertebrates. Together, our data suggest that multiple,
evolutionarily conserved mechanisms for DSB repair exist in eukaryotes.
Furthermore, they imply that Ku binds to DSBs in vivo and promotes repair
both by enhancing accurate DNA end joining and by suppressing alternative
error-prone repair pathways. Finally, we report that yku80 mutant yeasts
display dramatic telomeric shortening, suggesting that, in addition to
recognising DNA damage, Ku also binds to naturally occurring chromosomal
ends. These findings raise the possibility that Ku protects chromosomal
termini from nucleolytic attack and functions as part of a telomeric length
sensing system.
ARTICLES
Identification of a Saccharomyces cerevisiae Ku80 homologue: roles in DNA double strand break rejoining and in telomeric maintenance
Wellcome/CRC Institute and Department of Zoology, Cambridge University, UK.
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Y.-L. Tsai, S.-F. Tseng, S.-H. Chang, C.-C. Lin, and S.-C. Teng Involvement of Replicative Polymerases, Tel1p, Mec1p, Cdc13p, and the Ku Complex in Telomere-Telomere Recombination Mol. Cell. Biol., August 15, 2002; 22(16): 5679 - 5687. [Abstract] [Full Text] [PDF]
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M. L. DuBois, Z. W. Haimberger, M. W. McIntosh, and D. E. Gottschling A Quantitative Assay for Telomere Protection in Saccharomyces cerevisiae Genetics, July 1, 2002; 161(3): 995 - 1013. [Abstract] [Full Text] [PDF]
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M. Frank-Vaillant and S. Marcand NHEJ regulation by mating type is exercised through a novel protein, Lif2p, essential to the Ligase IV pathway Genes & Dev., November 15, 2001; 15(22): 3005 - 3012. [Abstract] [Full Text] [PDF]
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D. A. Thrower and K. Bloom Dicentric Chromosome Stretching during Anaphase Reveals Roles of Sir2/Ku in Chromatin Compaction in Budding Yeast Mol. Biol. Cell, September 1, 2001; 12(9): 2800 - 2812. [Abstract] [Full Text] [PDF]
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M. E. Gallego and C. I. White RAD50 function is essential for telomere maintenance in Arabidopsis PNAS, February 13, 2001; 98(4): 1711 - 1716. [Abstract] [Full Text] [PDF]
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 J. McIlrath, S. D. Bouffler, E. Samper, A. Cuthbert, A. Wojcik, I. Szumiel, P. E. Bryant, A. C. Riches, A. Thompson, M. A. Blasco, et al. Telomere Length Abnormalities in Mammalian Radiosensitive Cells Cancer Res., February 1, 2001; 61(3): 912 - 915. [Abstract] [Full Text]
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J. A. Clikeman, G. J. Khalsa, S. L. Barton, and J. A. Nickoloff Homologous Recombinational Repair of Double-Strand Breaks in Yeast Is Enhanced by MAT Heterozygosity Through yKU-Dependent and -Independent Mechanisms Genetics, February 1, 2001; 157(2): 579 - 589. [Abstract] [Full Text]
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J Bertinato, C Schild-Poulter, and R. Hache Nuclear localization of Ku antigen is promoted independently by basic motifs in the Ku70 and Ku80 subunits J. Cell Sci., January 1, 2001; 114(1): 89 - 99. [Abstract] [PDF]
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N. Grandin, C. Damon, and M. Charbonneau Cdc13 Cooperates with the Yeast Ku Proteins and Stn1 To Regulate Telomerase Recruitment Mol. Cell. Biol., November 15, 2000; 20(22): 8397 - 8408. [Abstract] [Full Text]
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H.-L. Hsu, D. Gilley, S. A. Galande, M. P. Hande, B. Allen, S.-H. Kim, G. C. Li, J. Campisi, T. Kohwi-Shigematsu, and D. J. Chen Ku acts in a unique way at the mammalian telomere to prevent end joining Genes & Dev., November 15, 2000; 14(22): 2807 - 2812. [Abstract] [Full Text]
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P. Baumann and T. R. Cech Protection of Telomeres by the Ku Protein in Fission Yeast Mol. Biol. Cell, October 1, 2000; 11(10): 3265 - 3275. [Abstract] [Full Text]
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M. Takata, M. S. Sasaki, E. Sonoda, T. Fukushima, C. Morrison, J. S. Albala, S. M. A. Swagemakers, R. Kanaar, L. H. Thompson, and S. Takeda The Rad51 Paralog Rad51B Promotes Homologous Recombinational Repair Mol. Cell. Biol., September 1, 2000; 20(17): 6476 - 6482. [Abstract] [Full Text]
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E. Feldmann, V. Schmiemann, W. Goedecke, S. Reichenberger, and P. Pfeiffer DNA double-strand break repair in cell-free extracts from Ku80-deficient cells: implications for Ku serving as an alignment factor in non-homologous DNA end joining Nucleic Acids Res., July 1, 2000; 28(13): 2585 - 2596. [Abstract] [Full Text] [PDF]
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H. Tsubouchi and H. Ogawa Exo1 Roles for Repair of DNA Double-Strand Breaks and Meiotic Crossing Over in Saccharomyces cerevisiae Mol. Biol. Cell, July 1, 2000; 11(7): 2221 - 2233. [Abstract] [Full Text]
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 S. M. Gasser A Sense of the End Science, May 26, 2000; 288(5470): 1377 - 1379. [Abstract] [Full Text]
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L. Guarente Sir2 links chromatin silencing, metabolism, and aging Genes & Dev., May 1, 2000; 14(9): 1021 - 1026. [Full Text]
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J. C. Prescott and E. H. Blackburn Telomerase RNA Template Mutations Reveal Sequence-Specific Requirements for the Activation and Repression of Telomerase Action at Telomeres Mol. Cell. Biol., April 15, 2000; 20(8): 2941 - 2948. [Abstract] [Full Text]
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L. Lacroix, H. Lienard, E. Labourier, M. Djavaheri-Mergny, J. Lacoste, H. Leffers, J. Tazi, C. Helene, and J.-L. Mergny Identification of two human nuclear proteins that recognise the cytosine-rich strand of human telomeres in vitro Nucleic Acids Res., April 1, 2000; 28(7): 1564 - 1575. [Abstract] [Full Text] [PDF]
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S. J. DiBiase, Z.-C. Zeng, R. Chen, T. Hyslop, W. J. Curran Jr., and G. Iliakis DNA-dependent Protein Kinase Stimulates an Independently Active, Nonhomologous, End-Joining Apparatus Cancer Res., March 1, 2000; 60(5): 1245 - 1253. [Abstract] [Full Text]
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B. Fellerhoff, F. Eckardt-Schupp, and A. A. Friedl Subtelomeric Repeat Amplification Is Associated With Growth at Elevated Temperature in yku70 Mutants of Saccharomyces cerevisiae Genetics, March 1, 2000; 154(3): 1039 - 1051. [Abstract] [Full Text]
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S. Evans and V Lundblad Positive and negative regulation of telomerase access to the telomere J. Cell Sci., January 10, 2000; 113(19): 3357 - 3364. [Abstract] [PDF]
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 M.L. DUBOIS, S.J. DIEDE, A.E. STELLWAGEN, and D.E. GOTTSCHLING All Things Must End: Telomere Dynamics in Yeast Cold Spring Harb Symp Quant Biol, January 1, 2000; 65(0): 281 - 296. [Abstract] [PDF]
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S. M. Bailey, J. Meyne, D. J. Chen, A. Kurimasa, G. C. Li, B. E. Lehnert, and E. H. Goodwin DNA double-strand break repair proteins are required to cap the ends of mammalian chromosomes PNAS, December 21, 1999; 96(26): 14899 - 14904. [Abstract] [Full Text] [PDF]
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 C. Wang, M. A. Bogue, A. P. Nguyen, and D. B. Roth Irradiation-Induced Rescue of Thymocyte Differentiation and V(D)J Recombination in Mice Lacking the Catalytic Subunit of DNA-Dependent Protein Kinase J. Immunol., December 1, 1999; 163(11): 6065 - 6071. [Abstract] [Full Text] [PDF]
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H.-L. Hsu, D. Gilley, E. H. Blackburn, and D. J. Chen Ku is associated with the telomere in mammals PNAS, October 26, 1999; 96(22): 12454 - 12458. [Abstract] [Full Text] [PDF]
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M. Kaeberlein, M. McVey, and L. Guarente The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms Genes & Dev., October 1, 1999; 13(19): 2570 - 2580. [Abstract] [Full Text]
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J. A. Downs and S. P. Jackson Involvement of DNA End-Binding Protein Ku in Ty Element Retrotransposition Mol. Cell. Biol., September 1, 1999; 19(9): 6260 - 6268. [Abstract] [Full Text] [PDF]
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R. Kooistra, A. Pastink, J. B. M. Zonneveld, P. H. M. Lohman, and J. C. J. Eeken The Drosophila melanogaster DmRAD54 Gene Plays a Crucial Role in Double-Strand Break Repair after P-Element Excision and Acts Synergistically with Ku70 in the Repair of X-Ray Damage Mol. Cell. Biol., September 1, 1999; 19(9): 6269 - 6275. [Abstract] [Full Text] [PDF]
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R. J. Craven and T. D. Petes Dependence of the Regulation of Telomere Length on the Type of Subtelomeric Repeat in the Yeast Saccharomyces cerevisiae Genetics, August 1, 1999; 152(4): 1531 - 1541. [Abstract] [Full Text]
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