Cited by 1,166DNA Repair MechanismsCRISPR and Genetic EngineeringEffects of Radiation Exposure

Hairpin opening and overhang processing by an Artemis/DNA-dependent protein kinase complex in nonhomologous end joining and V(D)J recombination

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Ma, Yunmei, Pannicke, Ulrich, Schwarz, Klaus, Lieber, Michael R.·2002·Cell

Abstract

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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Crossref · 10.1016/s0092-8674(02)00671-2

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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
2026: 11 · 2025: 27 · 2024: 28 · 2023: 32 · 2022: 41 · 2021: 35 · 2020: 47 · 2019: 36 · 2018: 40 · 2017: 35 · 2016: 40 · 2015: 41 · 2014: 53 · 2013: 45 · 2012: 63
FWCI
29.20
Type
journal article
Language
en
Open access
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

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