Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double‐strand breaks
Open accessAbstract
Ku protein binds to DNA ends and is a cofactor for the DNA-dependent protein kinase. Both of these components are involved in DNA double-strand break repair, but it has not been clear if they function indirectly, by sensing DNA damage and activating other factors, or if they are more directly involved in the processing and rejoining of DNA breaks. We demonstrate that intermolecular ligation of DNA fragments is highly dependent on Ku under conditions designed to mimic those existing in the cell. This effect of Ku is specific to eukaryotic DNA ligases. Ku protein, therefore, has an activity consistent with a direct role in rejoining DNA breaks and independent of DNA-dependent protein kinase.
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The Ku complex, a Ku70/Ku80 heterodimer, is a major end-binding factor in mammalian cells and has end-bridging activity.
“It has been shown that Ku complex (a heterodimer of Ku70/Ku80 [≈86]) is a major end binding factor in mammalian cells, possess end bridging activity [308, 309].”
From Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair (2010) · cites this paper as [309]
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Cites
The DNA-dependent protein kinase: Requirement for DNA ends and association with Ku antigen
Gottlieb, T. M., & Jackson, S. P. (1993) · Cell · doi:10.1016/0092-8674(93)90057-w · Cited by 1,233 · see citing works
Activity of DNA ligase IV stimulated by complex formation with XRCC4 protein in mammalian cells
Grawunder, U., Wilm, M. S., Wu, X., Kulesza, P., Wilson, T. E., Mann, M., & Lieber, M. R. (1997) · Nature · doi:10.1038/41358 · Cited by 694 · see citing works
Boulton, S. J., & Jackson, S. P. (1996) · The EMBO Journal · doi:10.1002/j.1460-2075.1996.tb00890.x · Cited by 502 · see citing works
Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV
Critchlow, S. E., Bowater, R. P., & Jackson, S. P. (1997) · Current Biology · doi:10.1016/s0960-9822(06)00258-2 · Cited by 474 · see citing works
Li, Z., Otevrel, T., Gao, Y., Cheng, H.-L., Seed, B., Stamato, T. D., Taccioli, G. E., & Alt, F. W. (1995) · Cell · doi:10.1016/0092-8674(95)90135-3 · Cited by 458 · see citing works
Impairment of V(D)J Recombination in Double-Strand Break Repair Mutants
Taccioli, G. E., Rathbun, G. A., Oltz, E. M., Stamato, T. D., Jeggo, P. A., & Alt, F. W. (1993) · Science · doi:10.1126/science.8469973 · Cited by 451 · see citing works
Yeast DNA ligase IV mediates non-homologous DNA end joining
Wilson, T. E., Grawunder, U., & Lieber, M. R. (1997) · Nature · doi:10.1038/41365 · Cited by 418 · see citing works
Silencing factors participate in DNA repair and recombination in Saccharomyces cerevisiae
Tsukamoto, Y., Kato, J.-I., & Ikeda, H. (1997) · Nature · doi:10.1038/42288 · Cited by 332 · see citing works
Yaneva, M., Kowalewski, T., & Lieber, M. R. (1997) · The EMBO Journal · doi:10.1093/emboj/16.16.5098 · Cited by 324 · see citing works
Mechanisms of nonhomologous recombination in mammalian cells.
Roth, D. B., Porter, T. N., & Wilson, J. H. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.10.2599 · Cited by 314 · see citing works
Initiation of V(D)J recombination in a cell-free system
van Gent, D. C., McBlane, J. F., Ramsden, D. A., Sadofsky, M. J., Hesse, J. E., & Gellert, M. F. (1995) · Cell · doi:10.1016/0092-8674(95)90012-8 · Cited by 284 · see citing works
Self-citationde Vries, E., van Driel, W., Bergsma, W. G., Arnberg, A. C., & van der Vliet, P. C. (1989) · Journal of Molecular Biology · doi:10.1016/0022-2836(89)90088-0 · Cited by 276 · see citing works
DNA looping by Ku and the DNA-dependent protein kinase
Cary, R. B., Peterson, S. R., Wang, J., Bear, D. G., Bradbury, E. M., & Chen, D. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.9.4267 · Cited by 260 · see citing works
Wei, Y.-F., Robins, P., Carter, K., Caldecott, K. W., Pappin, D., Yu, G., Wang, R., Shell, B. K., Nash, R. A., Schär, P., et al. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.6.3206 · Cited by 260 · see citing works
Teo, S., & Jackson, S. P. (1997) · The EMBO Journal · doi:10.1093/emboj/16.15.4788 · Cited by 259 · see citing works
Functional interaction between DNA-PK and c-Abl in response to DNA damage
Kharbanda, S. M., Pandey, P., Jin, S., Inoue, S., Bharti, A. K., Yuan, Z.-M., Weichselbaum, R. R., Weaver, D. T., & Kufe, D. W. (1997) · Nature · doi:10.1038/386732a0 · Cited by 251 · see citing works
Menage á trois: Double strand break repair, V(D)J recombination and DNA‐PK
Jeggo, P. A., Taccioli, G. E., & Jackson, S. P. (1995) · BioEssays · doi:10.1002/bies.950171108 · Cited by 246 · see citing works
Falzon, M., Fewell, J. W., & Kuff, E. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82233-5 · Cited by 245 · see citing works
Lindahl, T. L., & Barnes, D. E. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.001343 · Cited by 232 · see citing works
Analysis of the mechanism of interaction of simian Ku protein with DNA
Paillard, S., & Strauss, F. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.20.5619 · Cited by 217 · see citing works
What to do at an end: DNA double-strand-break repair
Weaver, D. T. (1995) · Trends in Genetics · doi:10.1016/s0168-9525(00)89121-0 · Cited by 196 · see citing works
Schär, P., Herrmann, G., Daly, G., & Lindahl, T. L. (1997) · Genes & Development · doi:10.1101/gad.11.15.1912 · Cited by 190 · see citing works
V(D)J Recombination in Mammalian Cell Mutants Defective in DNA Double-Strand Break Repair
Pergola, F., Zdzienicka, M. Z., & Lieber, M. R. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.6.3464 · Cited by 189 · see citing works
Ku80-deficient Cells Exhibit Excess Degradation of Extrachromosomal DNA
Liang, F., & Jasin, M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.24.14405 · Cited by 174 · see citing works
Studies on mammalian mutants defective in rejoining double-strand breaks in DNA
Jeggo, P. A. (1990) · Mutation Research/Reviews in Genetic Toxicology · doi:10.1016/0165-1110(90)90028-a · Cited by 171 · see citing works
Ramsden, D. A., Paull, T. T., & Gellert, M. F. (1997) · Nature · doi:10.1038/41351 · Cited by 146 · see citing works
Self-citationBogue, M. A., Wang, C., Zhu, C., & Roth, D. B. (1997) · Immunity · doi:10.1016/s1074-7613(00)80508-7 · Cited by 138 · see citing works
DNA Ligase IV from HeLa Cell Nuclei
Robins, P., & Lindahl, T. L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.39.24257 · Cited by 129 · see citing works
Mechanisms of Nonhomologous Recombination in Mammalian Cells
Roth, D. B., Porter, T. N., & Wilson, J. H. (1985) · Molecular and Cellular Biology · doi:10.1128/mcb.5.10.2599-2607.1985 · Cited by 129 · see citing works
The DNA-dependent protein kinase, DNA-PK: 10 years and no ends in sight
Lees‐Miller, S. P. (1996) · Biochemistry and Cell Biology · doi:10.1139/o96-054 · Cited by 115 · see citing works
Ku proteins join DNA fragments as shown by atomic force microscopy.
Pang, D., Yoo, S., Dynan, W. S., Jung, M., & Dritschilo, A. (1997) · PubMed · Cited by 107 · see citing works
Mechanisms of Overlap Formation in Nonhomologous DNA End Joining
Pfeiffer, P., Thode, S., Hancke, J., & Vielmetter, W. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.2.888 · Cited by 106 · see citing works
Repair and Recombination: How to make ends meet
Roth, D. B., Lindahl, T. L., & Gellert, M. F. (1995) · Current Biology · doi:10.1016/s0960-9822(95)00101-1 · Cited by 100 · see citing works
Self-citationChan, D. W., Ting, N. S. Y., Lees‐Miller, S. P., et al. (1996) · Biochemistry and Cell Biology · doi:10.1139/o96-007 · Cited by 84 · see citing works
Ku Selectively Transfers between DNA Molecules with Homologous Ends
Bliss, T. M., & Lane, D. P. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.9.5765 · Cited by 78 · see citing works
Nomenclature of human genes involved in ionizing radiation sensitivity
Thompson, L. H., & Jeggo, P. A. (1995) · Mutation Research/DNA Repair · doi:10.1016/0921-8777(95)00018-f · Cited by 72 · see citing works
Production and characterization of recombinant human Ku antigen
Ono, M., Tucker, P. W., & Capra, J. D. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.19.3918 · Cited by 72 · see citing works
Wang, Y. C., Burkhart, W., Mackey, Z. B., et al. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)31783-6 · Cited by 68 · see citing works
V(D)J Recombination in Mammalian Cell Mutants Defective in DNA Double-Strand Break Repair
Pergola, F., Zdzienicka, M. Z., & Lieber, M. R. (1993) · Molecular and Cellular Biology · doi:10.1128/mcb.13.6.3464-3471.1993 · Cited by 54 · see citing works
Mechanisms of Overlap Formation in Nonhomologous DNA End Joining
Pfeiffer, P., Thode, S., Hancke, J., et al. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.2.888-895.1994 · Cited by 29 · see citing works
Elder, R. H., Montecucco, A., Ciarrocchi, G., et al. (1992) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1992.tb19826.x · Cited by 23 · see citing works
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Molecular Mechanisms of Mammalian DNA Repair and the DNA Damage Checkpoints
Sancar, A., Lindsey-Boltz, L. A., Ünsal-Kaçmaz, K., & Linn, S. (2004) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.73.011303.073723 · Cited by 3,317 · see citing works
Molecular Mechanisms of Ultraviolet Radiation‐Induced DNA Damage and Repair
Rastogi, R. P., Richa, Kumar, A., Tyagi, M. B., & Sinha, R. P. (2010) · Journal of Nucleic Acids · doi:10.4061/2010/592980 · Cited by 1,329 · see citing works
McEachern, M. J., Krauskopf, A., & Blackburn, E. H. (2000) · Annual Review of Genetics · doi:10.1146/annurev.genet.34.1.331 · Cited by 716 · see citing works
Nbs1 potentiates ATP-driven DNA unwinding and endonuclease cleavage by the Mre11/Rad50 complex
Paull, T. T., & Gellert, M. (1999) · Genes & Development · doi:10.1101/gad.13.10.1276 · Cited by 551 · see citing works
Self-citationDasika, G. K., Lin, S.-C. J., Zhao, S., Sung, P., Tomkinson, A., & Lee, E. Y.-H. P. (1999) · Oncogene · doi:10.1038/sj.onc.1203283 · Cited by 427 · see citing works
DNA end-joining catalyzed by human cell-free extracts
Baumann, P., & West, S. C. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.24.14066 · Cited by 295 · see citing works
Factors and forces controlling V(D) J recombination
Hesslein, D. G. T., & Schatz, D. G. (2001) · Advances in immunology · doi:10.1016/s0065-2776(01)78004-2 · Cited by 183 · see citing works
TRF2/RAP1 and DNA-PK mediate a double protection against joining at telomeric ends
Bombarde, O., Boby, C., Gomez, D., Frit, P., Giraud‐Panis, M., Gilson, E., Salles, B., & Calsou, P. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.49 · Cited by 89 · see citing works
Andrews, B. J., Lehman, J. A., & Turchi, J. J. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m512787200 · Cited by 49 · see citing works
- Authors
- Ramsden, D. A., & Gellert, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Gellert, Martin
- Venue
- The EMBO Journal
- Published
- 1998-01-15
- Volume
- 17
- Issue
- 2
- Pages
- 609-614
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1170410
- OpenAlex
- W2011320725
- Cited by
- 296
- References
- 41
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 7 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 8 · 2013: 9 · 2012: 6
- FWCI
- 11.63
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- Ku protein, DNA end joining, DNA double-strand break repair, DNA-dependent protein kinase, DNA end binding, DNA repair
- MeSH terms
- Ku Autoantigen, DNA Ligase ATP, Poly-ADP-Ribose Binding Proteins, DNA, DNA Damage, DNA Repair, DNA Helicases, DNA-Binding Proteins, Humans, Nuclear Proteins, DNA Ligases, Xenopus Proteins, Antigens, Nuclear
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