ArticleMolecular and cellular biology2010
Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 157 citations in OpenAlex.
- Activator mimicry by PP6 regulatory subunits directs Aurora A dephosphorylation in mitosis.The EMBO journal · 2026Article
- Epigenetic regulation of humoral immunity: molecular mechanisms, diseases and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Pp6-Pfkfb1 axis modulates intracellular bacterial proliferation by orchestrating host-pathogen metabolic crosstalk.PLoS pathogens · 2025Article
- Protein Phosphatase 2ACα Regulates ATR-Mediated Endogenous DNA Damage Response Against Microcephaly.Molecular neurobiology · 2025Article
- Functional Role of Protein Phosphatase-6 (Current medicinal chemistry · 2025Review
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- TIPRL1 and its ATM-dependent phosphorylation promote radiotherapy resistance in head and neck cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- High expression of PPP1CC promotes NHEJ-mediated DNA repair leading to radioresistance and poor prognosis in nasopharyngeal carcinoma.Cell death and differentiation · 2024Article
- Oncogenic K-RasFEBS open bio · 2024Article
- Protein phosphatase 6 promotes transforming growth factor-β signaling in mouse embryonic fibroblasts.The Journal of veterinary medical science · 2023Article
- How to fix DNA breaks: new insights into the mechanism of non-homologous end joining.Biochemical Society transactions · 2023Review
- Regulation of DNA damage and transcriptional output in the vasculature through a cytoglobin-HMGB2 axis.Redox biology · 2023Article
- Maintaining Genome Integrity: Protein Kinases and Phosphatases Orchestrate the Balancing Act of DNA Double-Strand Breaks Repair in Cancer.International journal of molecular sciences · 2023Review
- Cryo-EM visualization of DNA-PKcs structural intermediates in NHEJ.Science advances · 2023Article
- Heavy metal ions exchange driven protein phosphorylation cascade functions in genomic instability in spermatocytes and male infertility.Nucleic acids research · 2023Article
- Inducible protein degradation as a strategy to identify Phosphoprotein Phosphatase 6 substrates in RAS-mutant colorectal cancer cells.bioRxiv : the preprint server for biology · 2023Article
- Article
- Review
- PP6 negatively modulates LUBAC-mediated M1-ubiquitination of RIPK1 and c-FLIPCell death & disease · 2022Article
- Alternative splicing plays key roles in response to stress across different stages of fighting in the fish Betta splendens.BMC genomics · 2022Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 2 countries.
Funding
Abstract
The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) plays a major role in the repair of DNA double-strand breaks (DSBs) by nonhomologous end joining (NHEJ). We have previously shown that DNA-PKcs is autophosphorylated in response to ionizing radiation (IR) and that dephosphorylation by a protein phosphatase 2A (PP2A)-like protein phosphatase (PP2A, PP4, or PP6) regulates the protein kinase activity of DNA-PKcs. Here we report that DNA-PKcs interacts with the catalytic subunits of PP6 (PP6c) and PP2A (PP2Ac), as well as with the PP6 regulatory subunits PP6R1, PP6R2, and PP6R3. Consistent with a role in the DNA damage response, silencing of PP6c by small interfering RNA (siRNA) induced sensitivity to IR and delayed release from the G(2)/M checkpoint. Furthermore, siRNA silencing of either PP6c or PP6R1 led to sustained phosphorylation of histone H2AX on serine 139 (gamma-H2AX) after IR. In contrast, silencing of PP6c did not affect the autophosphorylation of DNA-PKcs on serine 2056 or that of the ataxia-telangiectasia mutated (ATM) protein on serine 1981. We propose that a novel function of DNA-PKcs is to recruit PP6 to sites of DNA damage and that PP6 contributes to the dephosphorylation of gamma-H2AX, the dissolution of IR-induced foci, and release from the G(2)/M checkpoint in vivo.
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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.