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Stimulation of the DNA-dependent Protein Kinase by Poly(ADP-Ribose) Polymerase
Open accessAbstract
The DNA-dependent protein kinase (DNA-PK) is a heterotrimeric enzyme that binds to double-stranded DNA and is required for the rejoining of double-stranded DNA breaks in mammalian cells. It has been proposed that DNA-PK functions in this DNA repair pathway by binding to the ends of broken DNA molecules and phosphorylating proteins that bind to the damaged DNA ends. Another enzyme that binds to DNA strand breaks and may also function in the cellular response to DNA damage is the poly(ADP-ribose) polymerase (PARP). Here, we show that PARP can be phosphorylated by purified DNA-PK, and the catalytic subunit of DNA-PK is ADP-ribosylated by PARP. The protein kinase activity of DNA-PK can be stimulated by PARP in the presence of NAD+ in a reaction that is blocked by the PARP inhibitor 1, 5-dihydroxyisoquinoline. The stimulation of DNA-PK by PARP-mediated protein ADP-ribosylation occurs independent of the Ku70/80 complex. Taken together, these results show that PARP can modify the activity of DNA-PK in vitro and suggest that these enzymes may function coordinately in vivo in response to DNA damage.
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Citations
Cited by
The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
Ray Chaudhuri, A., & Nussenzweig, A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.53 · Cited by 1,786
NAD+ metabolism: pathophysiologic mechanisms and therapeutic potential
Xie, N., Zhang, L., Gao, W., Huang, C., Huber, P. E., Zhou, X., Li, C., Shen, G., & Zou, B. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00311-7 · Cited by 1,052
Tankyrase, a Poly(ADP-Ribose) Polymerase at Human Telomeres
Smith, S., Giriat, I., Schmitt, A., & de Lange, T. (1998) · Science · doi:10.1126/science.282.5393.1484 · Cited by 1,012
Poly(ADP-ribosyl)ation by PARP-1: `PAR-laying' NAD+ into a nuclear signal
Kim, M. Y., Zhang, T., & Kraus, W. L. (2005) · Genes & Development · doi:10.1101/gad.1331805 · Cited by 802
Audebert, M., Salles, B., & Calsou, P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404524200 · Cited by 707
Metadata
- Authors
- Ruscetti, T., Lehnert, B. E., Halbrook, J., Le Trong, H., Hoekstra, M. F., Chen, D. J., & Peterson, S. R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1998-06
- Volume
- 273
- Issue
- 23
- Pages
- 14461-14467
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2075174658
- Cited by
- 248
- References
- 0
- FWCI
- 4.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- The paper
- Ruscetti, T., Lehnert, B. E., Halbrook, J., Le Trong, H., Hoekstra, M. F., Chen, D. J., & Peterson, S. R. (1998). Stimulation of the DNA-dependent Protein Kinase by Poly(ADP-Ribose) Polymerase. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.273.23.14461
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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