ArticleMolecular and cellular biology2014
Unraveling the complexities of DNA-dependent protein kinase autophosphorylation.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed.
- Nonhomologous end joining-the importance of end tethering and beyond.Genes & development · 2026Review
- DNA-PK: A synopsis beyond synapsis.DNA repair · 2024Review
- Secrets of DNA-PKcs beyond DNA repair.NPJ precision oncology · 2024Review
- BUB1 regulates non-homologous end joining pathway to mediate radioresistance in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2024Article
- BUB1 Inhibition Sensitizes TNBC Cell Lines to Chemotherapy and Radiotherapy.Biomolecules · 2024Article
- DNA-PK controls Apollo's access to leading-end telomeres.Nucleic acids research · 2024Article
- DNA-PK and ATM drive phosphorylation signatures that antagonistically regulate cytokine responses to herpesvirus infection or DNA damage.Cell systems · 2024Article
- OGT and OGA: Sweet guardians of the genome.The Journal of biological chemistry · 2024Review
- Comparative analysis of basal and etoposide-induced alterations in gene expression by DNA-PKcs kinase activity.Frontiers in genetics · 2024Article
- Unravelling the complexities of DNA-PK activation by structure-based mutagenesis.Research square · 2023Article
- How to fix DNA breaks: new insights into the mechanism of non-homologous end joining.Biochemical Society transactions · 2023Review
- Multifaceted Influence of Histone Deacetylases on DNA Damage Repair: Implications for Hepatocellular Carcinoma.Journal of clinical and translational hepatology · 2023Review
- Multi-OMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells.iScience · 2023Article
- Dynamics of the Artemis and DNA-PKcs Complex in the Repair of Double-Strand Breaks.Journal of molecular biology · 2022Review
- Structural analysis of the basal state of the Artemis:DNA-PKcs complex.Nucleic acids research · 2022Article
- The importance of DNAPKcs for blunt DNA end joining is magnified when XLF is weakened.Nature communications · 2022Article
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- Article
- Autophosphorylation transforms DNA-PK from protecting to processing DNA ends.Molecular cell · 2022Article
- Uncovering DNA-PKcs ancient phylogeny, unique sequence motifs and insights for human disease.Progress in biophysics and molecular biology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
DNA-dependent protein kinase (DNA-PK) orchestrates DNA repair by regulating access to breaks through autophosphorylations within two clusters of sites (ABCDE and PQR). Blocking ABCDE phosphorylation (by alanine mutation) imparts a dominant negative effect, rendering cells hypersensitive to agents that cause DNA double-strand breaks. Here, a mutational approach is used to address the mechanistic basis of this dominant negative effect. Blocking ABCDE phosphorylation hypersensitizes cells to most types of DNA damage (base damage, cross-links, breaks, and damage induced by replication stress), suggesting that DNA-PK binds DNA ends that result from many DNA lesions and that blocking ABCDE phosphorylation sequesters these DNA ends from other repair pathways. This dominant negative effect requires DNA-PK's catalytic activity, as well as phosphorylation of multiple (non-ABCDE) DNA-PK catalytic subunit (DNA-PKcs) sites. PSIPRED analysis indicates that the ABCDE sites are located in the only contiguous extended region of this huge protein that is predicted to be disordered, suggesting a regulatory role(s) and perhaps explaining the large impact ABCDE phosphorylation has on the enzyme's function. Moreover, additional sites in this disordered region contribute to the ABCDE cluster. These data, coupled with recent structural data, suggest a model whereby early phosphorylations promote initiation of nonhomologous end joining (NHEJ), whereas ABCDE phosphorylations, potentially located in a "hinge" region between the two domains, lead to regulated conformational changes that initially promote NHEJ and eventually disengage NHEJ.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.