The DNA-dependent protein kinase catalytic subunit phosphorylation sites in human Artemis
Open accessAbstract
Artemis protein has irreplaceable functions in V(D)J recombination and nonhomologous end joining (NHEJ) as a hairpin and 5' and 3' overhang endonuclease. The kinase activity of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is necessary in activating Artemis as an endonuclease. Here we report that three basal phosphorylation sites and 11 DNA-PKcs phosphorylation sites within the mammalian Artemis are all located in the C-terminal domain. All but one of these phosphorylation sites deviate from the SQ or TQ motif of DNA-PKcs that was predicted previously from in vitro phosphorylation studies. Phosphatase-treated mammalian Artemis and Artemis that is mutated at the three basal phosphorylation sites still retain DNA-PKcs-dependent endonucleolytic activities, indicating that basal phosphorylation is not required for the activation. In vivo studies of Artemis lacking the C-terminal domain have been reported to be sufficient to complement V(D)J recombination in Artemis null cells. Therefore, the C-terminal domain may have a negative regulatory effect on the Artemis endonucleolytic activities, and phosphorylation by DNA-PKcs in the C-terminal domain may relieve this inhibition.
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DNA-PK phosphorylates and activates downstream effectors.
“DNA-PK is believed to phosphorylate and activate downstream effectors [61].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [61]
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- Authors
- Ma, Y., Pannicke, U., Lu, H., Niewolik, D., Schwarz, K., & Lieber, M. R.
- Affiliations
- University of Southern California (US)
- Universität Ulm (DE)
- Corresponding author
- Schwarz, Klaus
- Lieber, Michael R.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 280
- Issue
- 40
- Pages
- 33839-33846
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2088698677
- Cited by
- 144
- References
- 32
- Citations by year
- 2026: 1 · 2024: 3 · 2023: 5 · 2022: 6 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 11 · 2012: 9
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- University of Virginia
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Keywords
- Artemis, DNA-PKcs, phosphorylation sites, C-terminal domain, V(D)J recombination, non-homologous end joining, endonuclease activation, phosphatase treatment
- MeSH terms
- DNA, DNA-Binding Proteins, Endonucleases, Humans, Nuclear Proteins, Phosphorylation, Plasmids, Recombination, Genetic, Polymerase Chain Reaction, Mutagenesis, Site-Directed, Baculoviridae, Catalytic Domain, DNA-Activated Protein Kinase
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