Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination
Open accessAbstract
Mutations in the Artemis protein in humans result in hypersensitivity to DNA double-strand break-inducing agents and absence of B and T lymphocytes (radiosensitive severe combined immune deficiency [RS-SCID]). Here, we report that Artemis forms a complex with the 469 kDa DNA-dependent protein kinase (DNA-PKcs) in the absence of DNA. The purified Artemis protein alone possesses single-strand-specific 5' to 3' exonuclease activity. Upon complex formation, DNA-PKcs phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and 3' overhangs, as well as hairpins. Finally, the Artemis:DNA-PKcs complex can open hairpins generated by the RAG complex. Thus, DNA-PKcs regulates Artemis by both phosphorylation and complex formation to permit enzymatic activities that are critical for the hairpin-opening step of V(D)J recombination and for the 5' and 3' overhang processing in nonhomologous DNA end joining.
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Artemis nuclease is responsible for end processing.
“The Artemis nuclease is responsible for end processing since blunt DNA ends are not always generated, especially after IR.”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [62]
Artemis utilizes a 5′ exonuclease and a 5′-3′ endonuclease to manipulate ssDNA overhangs for end processing.
“Artemis utilizes a 5′ exonuclease and a 5′–3′ endonuclease to manipulate ssDNA overhangs for end processing [62,63].”
From Integration of DNA damage and repair with murine double-minute 2 (Mdm2) in tumorigenesis (2012) · cites this paper as [62]
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- Authors
- Ma, Y., Pannicke, U., Schwarz, K., & Lieber, M. R.
- Affiliations
- USC Norris Comprehensive Cancer Center (US)
- Universität Ulm (DE)
- Corresponding author
- Lieber, Michael R.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-03
- Volume
- 108
- Issue
- 6
- Pages
- 781-794
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2011522975
- Cited by
- 1,166
- References
- 71
- Citations by year
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- FWCI
- 29.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- Artemis, DNA-dependent protein kinase, DNA-PKcs, non-homologous end joining, V(D)J recombination, phosphorylation, DNA double-strand breaks, endonuclease activity
- MeSH terms
- Adenosine Triphosphate, Animals, beta-Lactamases, DNA-Binding Proteins, DNA, Single-Stranded, Endonucleases, Enzyme Activation, Humans, Nuclear Proteins, Phosphorylation, Recombination, Genetic, Protein Serine-Threonine Kinases, Homeodomain Proteins, HMGB1 Protein, DNA-Activated Protein Kinase
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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