The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.
Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks
Open accessAbstract
The DNA-dependent protein kinase catalytic subunit (DNA-PKCS) plays an important role during the repair of DNA double-strand breaks (DSBs). It is recruited to DNA ends in the early stages of the nonhomologous end-joining (NHEJ) process, which mediates DSB repair. To study DNA-PKCS recruitment in vivo, we used a laser system to introduce DSBs in a specified region of the cell nucleus. We show that DNA-PKCS accumulates at DSB sites in a Ku80-dependent manner, and that neither the kinase activity nor the phosphorylation status of DNA-PKCS influences its initial accumulation. However, impairment of both of these functions results in deficient DSB repair and the maintained presence of DNA-PKCS at unrepaired DSBs. The use of photobleaching techniques allowed us to determine that the kinase activity and phosphorylation status of DNA-PKCS influence the stability of its binding to DNA ends. We suggest a model in which DNA-PKCS phosphorylation/autophosphorylation facilitates NHEJ by destabilizing the interaction of DNA-PKCS with the DNA ends.
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Cites
Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage
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Chromosomal stability and the DNA double-stranded break connection
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Mechanism and regulation of human non-homologous DNA end-joining
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The DNA-dependent protein kinase
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Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks
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DNA end-joining: from yeast to man
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Molecular mechanisms of DNA double-strand break repair
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Self-citationChan, D. W., Chen, B. P.-C., Prithivirajsingh, S., Kurimasa, A., Story, M. D., Qin, J., & Chen, D. J. (2002) · Genes & Development · doi:10.1101/gad.1015202 · Cited by 479
Self-citationLi, 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
Dynamic assembly of end-joining complexes requires interaction between Ku70/80 and XRCC4
Mari, P.-O., Florea, B. I., Persengiev, S. P., Verkaik, N. S., Brüggenwirth, H. T., Modesti, M., Giglia-Mari, G., Bezstarosti, K., Demmers, J. A. A., Luider, T. M., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0609061103 · Cited by 423
Self-citation
Cited by
Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications
Polo, S. E., & Jackson, S. P. (2011) · Genes & Development · doi:10.1101/gad.2021311 · Cited by 1,092
The mechanism of human nonhomologous DNA end joining
Lieber, M. R. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.r700039200 · Cited by 720
Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining
Mahaney, B. L., Meek, K., & Lees-Miller, S. P. (2009) · Biochemical Journal · doi:10.1042/bj20080413 · Cited by 717
Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining
Miller, K. M., Tjeertes, J. V., Coates, J., Legube, G., Polo, S. E., Britton, S., & Jackson, S. P. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1899 · Cited by 629
Heavy ion carcinogenesis and human space exploration
Durante, M., & Cucinotta, F. A. (2008) · Nature Reviews Cancer · doi:10.1038/nrc2391 · Cited by 578
Metadata
- Authors
- Uematsu, N., Weterings, E., Yano, K.-I., Morotomi-Yano, K., Jakob, B., Taucher-Scholz, G., Mari, P.-O., van Gent, D. C., Chen, B. P. C., & Chen, D. J.
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2007-04-16
- Volume
- 177
- Issue
- 2
- Pages
- 219-229
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- OpenAlex
- W2156063202
- Cited by
- 414
- References
- 37
- FWCI
- 10.06
- Type
- journal article
- Language
- en
- Open access
- green
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- Uematsu, N., Weterings, E., Yano, K.-I., Morotomi-Yano, K., Jakob, B., Taucher-Scholz, G., Mari, P.-O., van Gent, D. C., Chen, B. P. C., & Chen, D. J. (2007). Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks. The Journal of Cell Biology. https://doi.org/10.1083/jcb.200608077
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