ArticleOncogenesis2014
DNA-PKcs activates the Chk2-Brca1 pathway during mitosis to ensure chromosomal stability.
Article in Oncogenesis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 50 citations in OpenAlex.
- Loss of Nemp1 disrupts female meiosis and activates a conserved ATM-CHK2 checkpoint.Nature communications · 2026Article
- NKX6.3 modulation of mitotic dynamics and genomic stability in gastric carcinogenesis.Cell communication and signaling : CCS · 2025Article
- Chk2 sustains PLK1 activity in mitosis to ensure proper chromosome segregation.Nature communications · 2024Article
- PDLIM1 sustains DNA damage response by promoting chromatin relaxation and activating DNA-PK complex.Genes & diseases · 2024Article
- Phenethyl isothiocyanate and dasatinib combination synergistically reduces hepatocellular carcinoma growth via cell cycle arrest and oxeiptosis.Frontiers in pharmacology · 2023Article
- CHK2 activation contributes to the development of oxaliplatin resistance in colorectal cancer.British journal of cancer · 2022Article
- Article
- DNA-PKcs: A Targetable Protumorigenic Protein Kinase.Cancer research · 2022Review
- Genotoxicity-Stimulated and CYLD-Driven Malignant Transformation.Cancer management and research · 2022Article
- CtBP1/2 differentially regulate genomic stability and DNA repair pathway in high-grade serous ovarian cancer cell.Oncogenesis · 2021Article
- Mitotic and DNA Damage Response Proteins: Maintaining the Genome Stability and Working for the Common Good.Frontiers in cell and developmental biology · 2021Review
- DNA-PKcs inhibition impairs HDAC6-mediated HSP90 chaperone function on Aurora A and enhances HDACs inhibitor-induced cell killing by increasing mitotic aberrant spindle assembly.Cell cycle (Georgetown, Tex.) · 2021Article
- Review
- Kv10.1 Regulates Microtubule Dynamics during Mitosis.Cancers · 2020Article
- Review
- Review
- PARP inhibitors in ovarian cancer: Sensitivity prediction and resistance mechanisms.Journal of cellular and molecular medicine · 2019Review
- DNA-PK as an Emerging Therapeutic Target in Cancer.Frontiers in oncology · 2019Review
- Assessment of DNA-PKcs kinase activity by quantum dot-based microarray.Scientific reports · 2018Article
- Hydroxylated-Graphene Quantum Dots Induce DNA Damage and Disrupt Microtubule Structure in Human Esophageal Epithelial Cells.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is known to have a critical role in DNA double-strand break repair. We have previously reported that DNA-PKcs is activated when cells enter mitosis and functions in mitotic spindle assembly and chromosome segregation. Here we report that DNA-PKcs is the upstream regulator of the Chk2-Brca1 pathway, which impacts microtubule dynamics, kinetochore attachment and chromosomal segregation in mitosis. Downstream from Chk2, Brca1 promotes monoubiquitination of γ-tubulin to inhibit microtubule nucleation and growth. We found that DNA-PKcs is essential for mitotic Chk2 phosphorylation at Thr68. As in Chk2- and Brca1-deficient cells, loss of DNA-PKcs resulted in chromosome misalignment and lagging during anaphase owing to elevation in microtubule dynamics. Importantly, these mitotic aberrations in DNA-PKcs-defective cells were alleviated by the overexpression of phosphomimetic Chk2 or Brca1 mutant proteins but not their wild-type counterparts. Taken together, these results demonstrate that DNA-PKcs regulates mitotic spindle organization and chromosomal instability via the Chk2-Brca1 signaling pathway.
Identifiers
What OpenQuestion holds
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.