The Artemis:DNA-PKcs endonuclease cleaves DNA loops, flaps, and gaps.
In eukaryotic cells, nonhomologous DNA end joining (NHEJ) is a major pathway for repair of double-strand DNA breaks (DSBs). Artemis and the 469kDa DNA-dependent protein kinase (DNA-PKcs) together form a key nuclease for NHEJ in vertebrate organisms. The structure-specific endonucleolytic activity of Artemis is activated by binding to and phosphorylation ... by DNA-PKcs. We tested various DNA structures in order to understand the range of structural features that are recognized by the Artemis:DNA-PKcs complex. We find that all tested substrates that contain single-to-double-strand transitions can be cleaved by the Artemis:DNA-PKcs complex near the transition region. The cleaved substrates include heterologous loops, stem-loops, flaps, and gapped substrates. Such versatile activity on single-/double-strand transition regions is important in understanding how reconstituted NHEJ systems that lack DNA polymerases can join incompatible DNA ends and yet preserve 3' overhangs. Additionally, the flexibility of the Artemis:DNA-PKcs nuclease may be important in removing secondary structures that hinder processing of DNA ends during NHEJ.
Mesh Terms:
DNA, DNA, Single-Stranded, DNA-Activated Protein Kinase, DNA-Binding Proteins, Humans, Nuclear Proteins, Nucleic Acid Conformation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Recombination, Genetic, Substrate Specificity
DNA, DNA, Single-Stranded, DNA-Activated Protein Kinase, DNA-Binding Proteins, Humans, Nuclear Proteins, Nucleic Acid Conformation, Protein-Serine-Threonine Kinases, Recombinant Proteins, Recombination, Genetic, Substrate Specificity
DNA Repair (Amst.)
Date: Jul. 12, 2005
PubMed ID: 15936993
View in: Pubmed Google Scholar
Download Curated Data For This Publication
151140
Switch View:
- Interactions 1