PRKDC

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0000460 maturation of 5.8S rRNA	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	KEEP AS NON CORE	Summary: DNA-PKcs kinase activity and T2609-cluster phosphorylation are needed for normal pre-rRNA processing in a Ku-dependent nucleolar role. Reason: Shao et al. (2020) show kinase-dead and phospho-site mutant DNA-PKcs cells accumulate the 21S and 12S pre-rRNA precursors (12S being the 5.8S precursor). The function is real but secondary to the gene's NHEJ role, so it is kept as non-core. Supporting Evidence: PMID:32103174 revealed partial accumulation of the 21S and 12S pre-rRNA precursors of the 18S and 5.8S rRNAs, respectively PMID:32103174 Together our data show that DNA-PK has RNA-dependent, cNHEJ-independent functions during ribosome biogenesis that require the kinase activity of DNA-PKcs and its phosphorylation at the T2609 cluster.
GO:0000723 telomere maintenance	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: DNA-PKcs contributes to telomere stability; PAINT places this at the DNA-PKcs node (PTN001673367) with human and mouse experimental seeds. Reason: PRKDC sits inside the DNA-PKcs clade that carries the IBD; the target appearing in WITH/FROM reflects its own experimental grounding. Human DNA-PKcs-null cells have altered telomere length, and UniProt records a telomere end-protection role by similarity. The telomere role is real but peripheral to NHEJ. Supporting Evidence: PMID:18710952 The catalytic subunit of DNA-dependent protein kinase regulates proliferation, telomere length, and genomic stability in human somatic cells. file:human/PRKDC/PRKDC-uniprot.txt Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion
GO:0000781 chromosome, telomeric region	HDA PMID:19135898 Purification of proteins associated with specific genomic Lo...	KEEP AS NON CORE	Summary: Identified in proteomics of isolated telomeric chromatin (PICh). Reason: High-throughput telomeric chromatin purification is consistent with DNA-PKcs presence at chromosome ends noted by UniProt. Location is accepted as non-core. Supporting Evidence: PMID:19135898 Purification of human telomeric chromatin using PICh identified the majority of known telomeric factors and uncovered a large number of novel associations. file:human/PRKDC/PRKDC-uniprot.txt Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion
GO:0000785 chromatin	IDA PMID:29478807 The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-M...	ACCEPT	Summary: DNA-PKcs acts on chromatin at DNA double-strand breaks, where it phosphorylates chromatin-bound substrates such as ASF1A and nucleosomal H2AX. Reason: DNA-PKcs is recruited by Ku to broken DNA ends in chromatin; Huang et al. show DNA-PKcs-dependent ASF1A phosphorylation that recruits ASF1A to chromatin, and nucleosomal H2AX is a DNA-PK substrate. is_active_in chromatin is an appropriate location for the core activity. Supporting Evidence: PMID:29478807 these data show that ASF1A is rapidly phosphorylated after DSB induction, in a manner dependent on DNA-PKcs, leading to its enrichment/recruitment to chromatin. PMID:14627815 Here we show that DNA-PK can be activated by nucleosomes through the ability of Ku to bind to the ends of nucleosomal DNA, and that the activated DNA-PK is capable of phosphorylating H2AX within the nucleosomes.
GO:0001933 negative regulation of protein phosphorylation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Transferred from mouse Prkdc, apparently from the effect on CRY1 Ser-588 phosphorylation in circadian studies, which UniProt describes as most likely indirect. Reason: DNA-PKcs is itself a protein kinase; reduced phosphorylation of one substrate (CRY1) by another kinase through an indirect mechanism is not a general negative regulation of protein phosphorylation by PRKDC. This is an over-generalisation of a peripheral, indirect phenotype. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism
GO:0002218 activation of innate immune response	IDA PMID:28712728 HEXIM1 and NEAT1 Long Non-coding RNA Form a Multi-subunit Co...	KEEP AS NON CORE	Summary: DNA-PK is reported to promote DNA-triggered IRF3-dependent innate immune signalling, as part of the HEXIM1-NEAT1 HDP-RNP and as a cytoplasmic DNA sensor. Reason: Morchikh et al. show HDP-RNP remodelling by foreign DNA leads to activation of DNA-PKcs and IRF3, and Ferguson et al. independently describe DNA-PK as an IRF3-activating DNA sensor. Other work shows DNA-PK suppresses cGAS (row for GO:0160049), so the sign is context-dependent; this immune role is non-core. Supporting Evidence: PMID:28712728 Remodeling leads to the release of paraspeckle proteins, recruitment of STING, and activation of DNAPKc and IRF3. PMID:23251783 Here we identify DNA-dependent protein kinase (DNA-PK) as a DNA sensor that activates innate immunity.
GO:0003690 double-stranded DNA binding	IDA PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	ACCEPT	Summary: DNA-PKcs binds double-stranded DNA ends, alone or in the Ku-DNA holoenzyme; DNA binding is required for its kinase activity. Reason: Cryo-EM structures show DNA-PKcs bound to a DNA end alone and in the Ku70/80-DNA complex, and DNA binding allosterically activates the kinase. Double-stranded DNA binding is a core property of the DNA-dependent kinase. Supporting Evidence: PMID:33385326 Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms PMID:28840859 Structural and biochemical analyses indicate that KU70/80 and DNA coordinately induce conformational changes of DNA-PKcs and allosterically stimulate its kinase activity. file:human/PRKDC/PRKDC-uniprot.txt Must be bound to DNA to express its catalytic properties
GO:0003690 double-stranded DNA binding	IEA GO_REF:0000107	ACCEPT	Summary: DNA-PKcs binds double-stranded DNA ends, alone or in the Ku-DNA holoenzyme; DNA binding is required for its kinase activity. Reason: Cryo-EM structures show DNA-PKcs bound to a DNA end alone and in the Ku70/80-DNA complex, and DNA binding allosterically activates the kinase. Double-stranded DNA binding is a core property of the DNA-dependent kinase. Supporting Evidence: PMID:33385326 Here, we report the cryoelectron microscopy (cryo-EM) structures of DNA-PKcs (DNA-PK catalytic subunit) bound to a DNA end or complexed with Ku70/80 and DNA in both inactive and activated forms PMID:28840859 Structural and biochemical analyses indicate that KU70/80 and DNA coordinately induce conformational changes of DNA-PKcs and allosterically stimulate its kinase activity. file:human/PRKDC/PRKDC-uniprot.txt Must be bound to DNA to express its catalytic properties
GO:0003723 RNA binding	HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi...	KEEP AS NON CORE	Summary: Captured in an mRNA interactome screen by UV crosslinking. Reason: High-throughput RNA-interactome capture; DNA-PKcs RNA binding is independently supported by Ku-dependent assembly on U3 snoRNA and other cellular RNAs (PMID:32103174). RNA binding is real but peripheral to the core DNA-repair function. Supporting Evidence: PMID:22658674 We identify 860 proteins that qualify as RBPs by biochemical and statistical criteria PMID:32103174 U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609.
GO:0003723 RNA binding	HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ...	KEEP AS NON CORE	Summary: Captured in an mRNA interactome screen by UV crosslinking. Reason: High-throughput RNA-interactome capture; DNA-PKcs RNA binding is independently supported by Ku-dependent assembly on U3 snoRNA and other cellular RNAs (PMID:32103174). RNA binding is real but peripheral to the core DNA-repair function. Supporting Evidence: PMID:22681889 Application to a human embryonic kidney cell line identified close to 800 proteins. PMID:32103174 U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609.
GO:0004672 protein kinase activity	IDA PMID:7671312 DNA-dependent protein kinase catalytic subunit: a relative o...	MODIFY	Summary: DNA-PKcs is a protein kinase; the specific activity is DNA-dependent protein serine/threonine kinase activity. Reason: The general term is correct but less specific than the evidence: DNA-PKcs phosphorylates Ser/Thr residues ([ST]-Q motif) only when activated by DNA ends. Replace with the DNA-dependent protein kinase term already carried by the gene. Proposed replacements: DNA-dependent protein kinase activity Supporting Evidence: PMID:7671312 DNA-PK phosphorylates proteins but has no detectable activity toward lipids. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself. file:human/PRKDC/PRKDC-uniprot.txt Must be bound to DNA to express its catalytic properties
GO:0004672 protein kinase activity	IMP PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	MODIFY	Summary: DNA-PKcs is a protein kinase; the specific activity is DNA-dependent protein serine/threonine kinase activity. Reason: The general term is correct but less specific than the evidence: DNA-PKcs phosphorylates Ser/Thr residues ([ST]-Q motif) only when activated by DNA ends. Replace with the DNA-dependent protein kinase term already carried by the gene. Proposed replacements: DNA-dependent protein kinase activity Supporting Evidence: PMID:7671312 DNA-PK phosphorylates proteins but has no detectable activity toward lipids. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself. file:human/PRKDC/PRKDC-uniprot.txt Must be bound to DNA to express its catalytic properties
GO:0004672 protein kinase activity	TAS PMID:7671312 DNA-dependent protein kinase catalytic subunit: a relative o...	MODIFY	Summary: DNA-PKcs is a protein kinase; the specific activity is DNA-dependent protein serine/threonine kinase activity. Reason: The general term is correct but less specific than the evidence: DNA-PKcs phosphorylates Ser/Thr residues ([ST]-Q motif) only when activated by DNA ends. Replace with the DNA-dependent protein kinase term already carried by the gene. Proposed replacements: DNA-dependent protein kinase activity Supporting Evidence: PMID:7671312 DNA-PK phosphorylates proteins but has no detectable activity toward lipids. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself. file:human/PRKDC/PRKDC-uniprot.txt Must be bound to DNA to express its catalytic properties
GO:0004674 protein serine/threonine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: PIKK-family protein serine/threonine kinase activity propagated from the PTHR11139 root node (PTN000124197). Reason: Correct phylogenetic placement: PRKDC is a catalytically active PIKK; its own experimental annotation is among the descendant evidence, which is expected. The DNA-dependence is captured separately by GO:0004677. Supporting Evidence: PMID:20023628 DNA-PKcs is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids and belonging to the phosphatidylinositol-3-OH kinase (PI(3)K)-related protein family. file:human/PRKDC/PRKDC-uniprot.txt Belongs to the PI3/PI4-kinase family.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:15262962 Identification of a PKB/Akt hydrophobic motif Ser-473 kinase...	ACCEPT	Summary: Feng et al. purified a PKB Ser-473 kinase activity and identified it as DNA-PK, which phosphorylates PKB Ser-473 in vitro. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:15262962 In vitro, DNA-PK phosphorylated PKB on Ser-473, resulting in a approximately 10-fold enhancement of PKB activity. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon...	ACCEPT	Summary: Wong et al. show DNA-PK phosphorylates USF-1 on feeding/insulin signalling at the FAS promoter. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:19303849 feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:24485452 DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3.	ACCEPT	Summary: Farber-Katz et al. show DNA-PK directly phosphorylates GOLPH3 after DNA damage. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:24485452 In response to DNA damage, DNA-PK phosphorylates GOLPH3, resulting in increased interaction with MYO18A, which applies a tensile force to the Golgi. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:26237645 Local generation of fumarate promotes DNA repair through inh...	ACCEPT	Summary: Jiang et al. show purified activated DNA-PK phosphorylates fumarase (FH) at Thr236. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:26237645 an in vitro protein phosphorylation assay showed that purified, activated DNA-PK phosphorylated purified recombinant FH PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:29478807 The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-M...	ACCEPT	Summary: Huang et al. show DNA-PKcs-dependent phosphorylation of ASF1A Ser192 after DSBs. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:29478807 ASF1A is phosphorylated on serine 192 in a manner dependent on DNA-PKcs in response to DSBs PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	ACCEPT	Summary: Shao et al. show U3 snoRNA-activated DNA-PK autophosphorylation at the T2609 cluster. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:32103174 U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:33273464 DNA-PK deficiency potentiates cGAS-mediated antiviral innate...	ACCEPT	Summary: Sun et al. show DNA-PK phosphorylates cGAS. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:33273464 we report that DNA-PK phosphorylates cGAS and suppresses its enzymatic activity. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi...	ACCEPT	Summary: Wang et al. show activated DNA-PK phosphorylates PARP1 on Thr594. Reason: Direct substrate phosphorylation by DNA-PK on Ser/Thr residues supports protein serine/threonine kinase activity, the core catalytic activity of PRKDC (its DNA-dependence is captured by GO:0004677). Supporting Evidence: PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo. PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0004674 protein serine/threonine kinase activity	IEA GO_REF:0000003	ACCEPT	Summary: EC 2.7.11.1 mapping to protein serine/threonine kinase activity. Reason: Consistent with the curated catalytic activity (Ser and Thr phosphorylation) and extensive experimental evidence. Supporting Evidence: PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself. PMID:20023628 DNA-PKcs is a serine/threonine protein kinase comprising a single polypeptide chain of 4,128 amino acids and belonging to the phosphatidylinositol-3-OH kinase (PI(3)K)-related protein family.
GO:0004674 protein serine/threonine kinase activity	TAS Reactome:R-HSA-5687183	ACCEPT	Summary: Reactome: PRKDC phosphorylates Artemis (DCLRE1C) at DSBs. Reason: Artemis S516 phosphorylation by DNA-PKcs activates Artemis endonuclease in NHEJ and V(D)J hairpin opening; supports Ser/Thr kinase activity. Supporting Evidence: Reactome:R-HSA-5687183 PRKDC (DNA-PKcs) phosphorylates DCLRE1C (ARTEMIS) at least on serine residue S516, and this phosphorylation is necessary for the activation of DCLRE1C endonucleolytic activity PMID:11955432 Upon complex formation, DNA-PKcs phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and 3' overhangs, as well as hairpins.
GO:0004677 DNA-dependent protein kinase activity	IDA PMID:15194694 Phosphorylation and regulation of DNA ligase IV stability by...	ACCEPT	Summary: DNA-PK phosphorylates DNA ligase IV (Thr650) in vitro. Reason: DNA-dependent Ser/Thr kinase activity is the defining catalytic activity of PRKDC; activity requires Ku and DNA ends. Supporting Evidence: PMID:15194694 Using tandem mass spectrometry, we identified a DNA-PK phosphorylation site at Thr-650 in human Lig4 PMID:28840859 Structural and biochemical analyses indicate that KU70/80 and DNA coordinately induce conformational changes of DNA-PKcs and allosterically stimulate its kinase activity. file:human/PRKDC/PRKDC-uniprot.txt Must be bound to DNA to express its catalytic properties
GO:0004677 DNA-dependent protein kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation of DNA-dependent protein kinase activity (InterPro DNA-PK domain, mouse ortholog). Reason: Correct and core; consistent with experimental evidence. Supporting Evidence: PMID:28840859 Structural and biochemical analyses indicate that KU70/80 and DNA coordinately induce conformational changes of DNA-PKcs and allosterically stimulate its kinase activity. file:human/PRKDC/PRKDC-uniprot.txt Must be bound to DNA to express its catalytic properties
GO:0005515 protein binding	IPI PMID:17308091 A role for the HOXB7 homeodomain protein in DNA repair.	REMOVE	Summary: Protein binding with HOXB7 (PMID:17308091). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with HOXB7 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:17308091 included members of the DNA-dependent protein kinase holoenzyme (Ku70, Ku80, DNA-PK(cs)) responsible for DNA double-strand break repair by nonhomologous end joining pathway
GO:0005515 protein binding	IPI PMID:17308091 A role for the HOXB7 homeodomain protein in DNA repair.	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:17308091). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:17308091 A role for the HOXB7 homeodomain protein in DNA repair.	REMOVE	Summary: Protein binding with XRCC5 (Ku80) (PMID:17308091). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:18026119 A YY1-INO80 complex regulates genomic stability through homo...	REMOVE	Summary: Protein binding with YY1 (PMID:18026119). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with YY1 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false.
GO:0005515 protein binding	IPI PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon...	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:19303849). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon...	REMOVE	Summary: Protein binding with XRCC5 (Ku80) (PMID:19303849). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:19833092 Ku proteins function as corepressors to regulate farnesoid X...	REMOVE	Summary: Protein binding with NR1H4 (FXR) (PMID:19833092). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with NR1H4 (FXR) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:19833092 We identified DNA-dependent protein kinase catalytic subunit (DNA-PKcs), Ku80, and Ku70 as FXR associated factors.
GO:0005515 protein binding	IPI PMID:20023628 Crystal structure of DNA-PKcs reveals a large open-ring crad...	REMOVE	Summary: Protein binding with XRCC5 (Ku80) (PMID:20023628). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:20085707 Aire's partners in the molecular control of immunological to...	REMOVE	Summary: Protein binding with AIRE (PMID:20085707). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with AIRE does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:20085707 One set of Aire interactions centered on DNA protein kinase and a group of proteins it partners with to resolve DNA double-stranded breaks or promote transcriptional elongation.
GO:0005515 protein binding	IPI PMID:20085707 Aire's partners in the molecular control of immunological to...	REMOVE	Summary: Protein binding with XRCC5 (Ku80) (PMID:20085707). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:20711232 Regulation of DNA-dependent protein kinase by protein kinase...	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:20711232). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:20711232 Regulation of DNA-dependent protein kinase by protein kinase...	REMOVE	Summary: Protein binding with XRCC5 (Ku80) (PMID:20711232). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:21575865 Mechanistic rationale for inhibition of poly(ADP-ribose) pol...	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:21575865). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:21575865 Mechanistic rationale for inhibition of poly(ADP-ribose) pol...	REMOVE	Summary: Protein binding with ETS1 (PMID:21575865). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with ETS1 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:21575865 interacts in a DNA-independent manner with the enzyme poly (ADP-ribose) polymerase 1 (PARP1) and the catalytic subunit of DNA protein kinase (DNA-PKcs)
GO:0005515 protein binding	IPI PMID:21575865 Mechanistic rationale for inhibition of poly(ADP-ribose) pol...	REMOVE	Summary: Protein binding with SPI1 (PMID:21575865). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with SPI1 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false.
GO:0005515 protein binding	IPI PMID:21575865 Mechanistic rationale for inhibition of poly(ADP-ribose) pol...	REMOVE	Summary: Protein binding with ETV1 (PMID:21575865). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with ETV1 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false.
GO:0005515 protein binding	IPI PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	REMOVE	Summary: Protein binding with PARP1/Ku (PMID:22504299). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	REMOVE	Summary: Protein binding with PARP1/WARS1 (PMID:22504299). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with PARP1/WARS1 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells.
GO:0005515 protein binding	IPI PMID:22529269 Artemis C-terminal region facilitates V(D)J recombination th...	REMOVE	Summary: Protein binding with DCLRE1C (Artemis) (PMID:22529269). Reason: Generic protein binding is uninformative. The Artemis interaction is real and functionally important (DNA-PKcs phosphorylates and activates Artemis), which is captured by the kinase activity, NHEJ and V(D)J recombination terms. Removal does not dispute the interaction. Supporting Evidence: PMID:22529269 Point mutations in Artemis that disrupt its interaction with Ligase IV or DNA-PKcs reduce V(D)J recombination PMID:11955432 Upon complex formation, DNA-PKcs phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and 3' overhangs, as well as hairpins.
GO:0005515 protein binding	IPI PMID:22977523 Functional interaction of BRCA1/ATM-associated BAAT1 with th...	REMOVE	Summary: Protein binding with BRAT1 (BAAT1) (PMID:22977523). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with BRAT1 (BAAT1) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:22977523 BAAT1 was found to bind to the DNA-PK catalytic subunit (DNA-PKcs) and SMC1
GO:0005515 protein binding	IPI PMID:24365180 DNA-dependent protein kinase catalytic subunit (DNA-PKcs)-SI...	REMOVE	Summary: Protein binding with MAPKAP1 (SIN1) (PMID:24365180). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with MAPKAP1 (SIN1) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:24365180 we discovered that DNA-PKcs was associated with SIN1 in cytosol upon UVB radiation
GO:0005515 protein binding	IPI PMID:25303530 Enhancer activation requires trans-recruitment of a mega tra...	REMOVE	Summary: Protein binding with RARA (PMID:25303530). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with RARA does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false.
GO:0005515 protein binding	IPI PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ...	REMOVE	Summary: Protein binding with PARP1 (PMID:25749521). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with PARP1 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:25749521 The TNKS1BP1 protein was demonstrated to interact with DNA-dependent protein kinase (DNA-PKcs) and poly(ADP-ribose) polymerase 1 (PARP-1), by co-immunoprecipitation analysis.
GO:0005515 protein binding	IPI PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ...	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:25749521). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:25749521 TNKS1BP1 functions in DNA double-strand break repair though ...	REMOVE	Summary: Protein binding with TNKS1BP1 (PMID:25749521). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with TNKS1BP1 does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false.
GO:0005515 protein binding	IPI PMID:25852083 DNA-dependent protein kinase (DNA-PK) permits vascular smoot...	REMOVE	Summary: Protein binding with NR4A3 (NOR1) (PMID:25852083). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with NR4A3 (NOR1) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:25852083 Co-immunoprecipitation studies from VSM cell lysates demonstrated that DNA-PK forms a complex with NOR1.
GO:0005515 protein binding	IPI PMID:25941166 XLS (c9orf142) is a new component of mammalian DNA double-st...	REMOVE	Summary: Protein binding with DCLRE1C (Artemis) (PMID:25941166). Reason: Generic protein binding is uninformative. The Artemis interaction is real and functionally important (DNA-PKcs phosphorylates and activates Artemis), which is captured by the kinase activity, NHEJ and V(D)J recombination terms. Removal does not dispute the interaction. Supporting Evidence: PMID:25941166 Here we show using combined affinity purification and mass spectrometry that DNA-PKcs co-purifies with all known core NHEJ factors. PMID:11955432 Upon complex formation, DNA-PKcs phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and 3' overhangs, as well as hairpins.
GO:0005515 protein binding	IPI PMID:26175416 DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate...	REMOVE	Summary: Protein binding with AR (PMID:26175416). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with AR does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:26175416 these findings reveal that DNA-PKcs is found in complex with AR and facilitates AR-dependent transcriptional transactivation
GO:0005515 protein binding	IPI PMID:26175416 DNA-PKcs-Mediated Transcriptional Regulation Drives Prostate...	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:26175416). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:26237645 Local generation of fumarate promotes DNA repair through inh...	REMOVE	Summary: Protein binding with FH (fumarase) (PMID:26237645). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with FH (fumarase) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false.
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:26496610). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:26496610 A human interactome in three quantitative dimensions organiz...	REMOVE	Summary: Protein binding with XRCC5 (Ku80) (PMID:26496610). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:32832608 TIP60 K430 SUMOylation attenuates its interaction with DNA-P...	REMOVE	Summary: Protein binding with KAT5 (TIP60) (PMID:32832608). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with KAT5 (TIP60) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:32832608 we demonstrate that the interaction of TIP60 with DNA-PKcs is attenuated specifically in S phase
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	REMOVE	Summary: Protein binding with DCLRE1C (Artemis) (PMID:33961781). Reason: Generic protein binding is uninformative. The Artemis interaction is real and functionally important (DNA-PKcs phosphorylates and activates Artemis), which is captured by the kinase activity, NHEJ and V(D)J recombination terms. Removal does not dispute the interaction. Supporting Evidence: PMID:11955432 Upon complex formation, DNA-PKcs phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and 3' overhangs, as well as hairpins.
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: Protein binding with XRCC6 (Ku70) (PMID:35271311). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce...	REMOVE	Summary: Protein binding with XRCC5 (Ku80) (PMID:35271311). Reason: Generic protein binding is uninformative. The Ku interaction is real and functionally central, but it is captured by the complex memberships (GO:0070418 DNA-dependent protein kinase complex, GO:0070419 NHEJ complex) and by DNA-dependent protein kinase activity. Removal does not dispute the interaction. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0005515 protein binding	IPI PMID:9442054 DNA-dependent protein kinase interacts with antigen receptor...	REMOVE	Summary: Protein binding with ILF2 (NF45) (PMID:9442054). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with ILF2 (NF45) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false. Supporting Evidence: PMID:9442054 antibodies to recombinant NF90 or recombinant NF45 immunoprecipitate DNA-PKcs in vitro
GO:0005515 protein binding	IPI PMID:9442054 DNA-dependent protein kinase interacts with antigen receptor...	REMOVE	Summary: Protein binding with ILF3 (NF90) (PMID:9442054). Reason: Generic protein binding is uninformative under the protein-binding policy. The reported interaction with ILF3 (NF90) does not by itself establish a more specific molecular function for DNA-PKcs; where DNA-PKcs phosphorylates the partner, that is captured by the kinase activity terms. Removal does not mean the interaction is false.
GO:0005634 nucleus	EXP PMID:12231622 Autophosphorylation of the DNA-dependent protein kinase cata...	ACCEPT	Summary: DNA-PKcs is a predominantly nuclear protein. Reason: Nuclear localization is well established and is where the core NHEJ and V(D)J functions occur. Supporting Evidence: PMID:12231622 Phosphorylated DNA-PKcs colocalizes with both gamma-H2AX and 53BP1 after DNA damage.
GO:0005634 nucleus	EXP PMID:14734805 DNA-PKcs function regulated specifically by protein phosphat...	ACCEPT	Summary: DNA-PKcs is a predominantly nuclear protein. Reason: Nuclear localization is well established and is where the core NHEJ and V(D)J functions occur. Supporting Evidence: PMID:14734805 DNA-PKcs, is a DNA-dependent serine/threonine kinase that phosphorylates protein targets as well as itself.
GO:0005634 nucleus	EXP PMID:15262962 Identification of a PKB/Akt hydrophobic motif Ser-473 kinase...	ACCEPT	Summary: DNA-PKcs is a predominantly nuclear protein. Reason: Nuclear localization is well established and is where the core NHEJ and V(D)J functions occur. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Nucleus
GO:0005634 nucleus	EXP PMID:22002106 Systematic analysis of protein pools, isoforms, and modifica...	ACCEPT	Summary: DNA-PKcs is a predominantly nuclear protein. Reason: Nuclear localization is well established and is where the core NHEJ and V(D)J functions occur. Supporting Evidence: PMID:22002106 we measured turnover rates and subcellular distribution for the HeLa cell proteome
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: Nuclear localization propagated across the PIKK family (PAINT). Reason: Correct for PRKDC; consistent with extensive experimental localization. Supporting Evidence: PMID:12231622 Phosphorylated DNA-PKcs colocalizes with both gamma-H2AX and 53BP1 after DNA damage. Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005634 nucleus	IDA PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	ACCEPT	Summary: DNA-PKcs is a predominantly nuclear protein. Reason: Nuclear localization is well established and is where the core NHEJ and V(D)J functions occur. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells.
GO:0005634 nucleus	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	ACCEPT	Summary: DNA-PKcs is a predominantly nuclear protein. Reason: Nuclear localization is well established and is where the core NHEJ and V(D)J functions occur. Supporting Evidence: PMID:32103174 DNA-PK, but not other cNHEJ factors, resides in nucleoli in an rRNA-dependent manner and is co-purified with the small subunit processome.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Electronic nucleus annotation. Reason: Consistent with experimental data. Supporting Evidence: PMID:12231622 Phosphorylated DNA-PKcs colocalizes with both gamma-H2AX and 53BP1 after DNA damage.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	ACCEPT	Summary: Human Protein Atlas immunofluorescence: nucleoplasm. Reason: Consistent with nuclear localization and diffuse nucleoplasmic staining reported independently. Supporting Evidence: PMID:27829214 ATM, DNA-PKcs (the catalytic subunit of DNA-PK) and Ku70 (a regulatory subunit of DNA-PK) were clearly localized to the nucleoli, in addition to showing diffuse staining throughout the nucleoplasm.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5686924	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5686924) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5687183	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5687183) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5687360	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5687360) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5693533	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5693533) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5693574	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5693574) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5693575	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5693575) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5693578	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5693578) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5693604	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5693604) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005654 nucleoplasm	TAS Reactome:R-HSA-5693615	ACCEPT	Summary: Reactome NHEJ reaction (Reactome:R-HSA-5693615) places PRKDC in the nucleoplasm at DNA DSBs. Reason: Nucleoplasm is the correct compartment for the NHEJ reactions in which DNA-PKcs participates. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0005667 transcription regulator complex	IDA PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon...	KEEP AS NON CORE	Summary: DNA-PK associates with USF-1 at the FAS promoter during feeding/insulin-induced transcription. Reason: Wong et al. identified DNA-PK among USF-1 interacting proteins at the FAS promoter; real but a context-specific transcriptional role, non-core. Supporting Evidence: PMID:19303849 feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation.
GO:0005730 nucleolus	IDA PMID:27829214 PICT-1 is a key nucleolar sensor in DNA damage response sign...	KEEP AS NON CORE	Summary: Immunostaining and nucleolar fractionation localize DNA-PKcs to nucleoli. Reason: Nucleolar localization is supported by two independent studies and relates to the non-core rRNA-processing role. Supporting Evidence: PMID:27829214 ATM, DNA-PKcs (the catalytic subunit of DNA-PK) and Ku70 (a regulatory subunit of DNA-PK) were clearly localized to the nucleoli, in addition to showing diffuse staining throughout the nucleoplasm.
GO:0005730 nucleolus	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	KEEP AS NON CORE	Summary: DNA-PK resides in nucleoli in an rRNA-dependent manner. Reason: Supports the non-core ribosome biogenesis role. Supporting Evidence: PMID:32103174 DNA-PK, but not other cNHEJ factors, resides in nucleoli in an rRNA-dependent manner and is co-purified with the small subunit processome.
GO:0005730 nucleolus	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location mapping: nucleolus. Reason: Consistent with experimental nucleolar localization; non-core. Supporting Evidence: PMID:32103174 DNA-PK, but not other cNHEJ factors, resides in nucleoli in an rRNA-dependent manner and is co-purified with the small subunit processome.
GO:0005829 cytosol	IEA GO_REF:0000044	KEEP AS NON CORE	Summary: UniProt subcellular location mapping: cytosol (based on Feng et al. 2004). Reason: A minor cytoplasmic pool is reported in several studies (AKT signalling, cytosolic DNA sensing); the core functions are nuclear. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Cytoplasm, cytosol Reactome:R-HSA-3134821 DNA-PK was found both in the nucleus and in the cytosol
GO:0005829 cytosol	TAS Reactome:R-HSA-3134821	KEEP AS NON CORE	Summary: Reactome: DNA-PK binds microbial dsDNA in the cytosol. Reason: Cytosolic DNA sensing is a non-core, debated role. Supporting Evidence: Reactome:R-HSA-3134821 DNA-PK was found both in the nucleus and in the cytosol PMID:23251783 Here we identify DNA-dependent protein kinase (DNA-PK) as a DNA sensor that activates innate immunity.
GO:0005829 cytosol	TAS Reactome:R-HSA-8938770	KEEP AS NON CORE	Summary: Reactome: RNF144A binds PRKDC in the cytoplasm. Reason: Cytoplasmic pool targeted for ubiquitination; non-core location. Supporting Evidence: Reactome:R-HSA-8938770 binds the catalytic subunit of DNA-dependent protein kinase (PRKDC, DNA-PKcs) and the E2-ubiquitin conjugate UBE2L3:Ubiquitin (UBCH7:Ubiquitin) located in the cytoplasm
GO:0005829 cytosol	TAS Reactome:R-HSA-8938773	KEEP AS NON CORE	Summary: Reactome: RNF144A polyubiquitinates PRKDC (cytosol). Reason: Cytoplasmic pool targeted for ubiquitination; non-core location. Supporting Evidence: Reactome:R-HSA-8938770 binds the catalytic subunit of DNA-dependent protein kinase (PRKDC, DNA-PKcs) and the E2-ubiquitin conjugate UBE2L3:Ubiquitin (UBCH7:Ubiquitin) located in the cytoplasm
GO:0005958 DNA-dependent protein kinase-DNA ligase 4 complex	IDA PMID:15194694 Phosphorylation and regulation of DNA ligase IV stability by...	ACCEPT	Summary: DNA-PKcs with Ku, XRCC4 and LIG4 forms the DNA-PK-DNA ligase 4 complex. Reason: Core NHEJ complex membership; Wang et al. used the Lig4-XRCC4 complex as a DNA-PK substrate. Supporting Evidence: PMID:15194694 Using tandem mass spectrometry, we identified a DNA-PK phosphorylation site at Thr-650 in human Lig4 file:human/PRKDC/PRKDC-uniprot.txt Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF
GO:0005958 DNA-dependent protein kinase-DNA ligase 4 complex	IDA PMID:34352203 Cryo-EM of NHEJ supercomplexes provides insights into DNA re...	ACCEPT	Summary: Cryo-EM structures of NHEJ supercomplexes containing Ku, DNA-PKcs, XRCC4, XLF and LIG4. Reason: Direct structural evidence of core complex membership. Supporting Evidence: PMID:34352203 Here, we present cryo-EM structures of NHEJ supercomplexes that are composed of these core proteins and DNA, revealing the detailed structural architecture of this assembly. PMID:33854234 Two DNA end-bound subcomplexes comprising Ku and DNA-PKcs are linked by interactions between the DNA-PKcs subunits and a scaffold comprising LigIV, XRCC4, XLF, XRCC4 and LigIV.
GO:0006281 DNA repair	IEA GO_REF:0000002	MODIFY	Summary: InterPro-based DNA repair annotation. Reason: Correct but general; the specific repair pathway in which DNA-PKcs acts is NHEJ, already annotated. Proposed replacements: double-strand break repair via nonhomologous end joining Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination
GO:0006302 double-strand break repair	IBA GO_REF:0000033	MODIFY	Summary: PAINT IBA for double-strand break repair at node PTN001673367. Reason: Correct but less specific than what is known for PRKDC: DNA-PKcs acts in DSB repair specifically via classical NHEJ, which the gene already carries (IEA, NAS, TAS). The node placement is not disputed. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN001673367 SUPPORTS TRANSFER Node placement is sound: PRKDC lies inside the DNA-PKcs clade and acts in DSB repair. The node term is correctly broad for the clade; for human PRKDC the more specific classical NHEJ term is directly supported, so the row is refined rather than disputed. UniProtKB:P78527 SUPPORTS TRANSFER The target's own experimental DSB-repair annotation is expected descendant evidence, not circularity. Proposed replacements: double-strand break repair via nonhomologous end joining Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination PMID:12231622 These findings establish that Ku-dependent phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by NHEJ.
GO:0006302 double-strand break repair	IMP PMID:18710952 The catalytic subunit of DNA-dependent protein kinase regula...	MODIFY	Summary: DNA-PKcs-null human somatic cells show DSB repair and genomic stability defects. Reason: Correct but general; the DSB-repair role of DNA-PKcs is in NHEJ, as stated in the same paper. Proposed replacements: double-strand break repair via nonhomologous end joining Supporting Evidence: PMID:18710952 DNA-PK functions in the nonhomologous end-joining pathway for the repair of DNA double-stranded breaks (DSBs) introduced by either exogenous DNA damage or endogenous processes, such as lymphoid V(D)J recombination. PMID:18710952 the cell line lacking this gene has profound proliferation and genomic stability deficits not observed for other mammalian systems.
GO:0006303 double-strand break repair via nonhomologous end joining	IEA GO_REF:0000120	ACCEPT	Summary: Electronic NHEJ annotation from DNA-PKcs-specific domains. Reason: Core function. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination PMID:12231622 These findings establish that Ku-dependent phosphorylation of DNA-PKcs at Thr2609 is required for the repair of DSBs by NHEJ.
GO:0006303 double-strand break repair via nonhomologous end joining	NAS PMID:10207111 Requirement for the kinase activity of human DNA-dependent p...	ACCEPT	Summary: Kinase activity of DNA-PKcs is required for DSB rejoining (NHEJ). Reason: Core function; kinase-dead constructs fail to complement DSB repair. Supporting Evidence: PMID:10207111 These DNA-PKcs mutant constructs are able to express the protein but fail to complement the DNA DSB or V(D)J recombination defects of DNA-PKcs mutant cells.
GO:0006303 double-strand break repair via nonhomologous end joining	TAS Reactome:R-HSA-5693571	ACCEPT	Summary: Reactome NHEJ pathway. Reason: Core function. Supporting Evidence: Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.
GO:0006338 chromatin remodeling	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: Inferred by inter-ontology link from histone H2AX S139 kinase activity. Reason: Phosphorylation of H2AX at DSBs is a signalling mark, not ATP-dependent chromatin remodelling by DNA-PKcs; the logical inference over-states the role. The underlying H2AX kinase activity is retained separately. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism
GO:0006468 protein phosphorylation	IDA PMID:26237645 Local generation of fumarate promotes DNA repair through inh...	ACCEPT	Summary: DNA-PK phosphorylates fumarase in vitro and in IR-treated cells. Reason: Protein phosphorylation is the process directly executed by DNA-PKcs kinase activity. Supporting Evidence: PMID:26237645 an in vitro protein phosphorylation assay showed that purified, activated DNA-PK phosphorylated purified recombinant FH
GO:0006974 DNA damage response	IDA PMID:26237645 Local generation of fumarate promotes DNA repair through inh...	ACCEPT	Summary: DNA-PK-dependent fumarase phosphorylation is part of the IR-induced DNA damage response at DSB regions. Reason: DNA-PKcs is a DNA damage sensor kinase; DNA damage response is appropriate for its signalling outputs. Supporting Evidence: PMID:26237645 this increases the accumulation of the Ku70-containing DNA-PK at DSB regions for non-homologous end-joining DNA repair and cell survival. file:human/PRKDC/PRKDC-uniprot.txt Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage
GO:0006974 DNA damage response	IDA PMID:29478807 The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-M...	ACCEPT	Summary: DNA-PKcs-dependent ASF1A phosphorylation after DSBs. Reason: DNA damage signalling by DNA-PKcs. Supporting Evidence: PMID:29478807 ASF1A is phosphorylated on serine 192 in a manner dependent on DNA-PKcs in response to DSBs file:human/PRKDC/PRKDC-uniprot.txt Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage
GO:0006974 DNA damage response	IDA PMID:35460603 Cytoplasmic PARP1 links the genome instability to the inhibi...	ACCEPT	Summary: Virus-induced DNA damage activates DNA-PK, which phosphorylates PARP1. Reason: DNA damage signalling by DNA-PKcs. Supporting Evidence: PMID:35460603 we report that DNA virus induces a reactive nitrogen species (RNS)-dependent DNA damage and activates DNA-dependent protein kinase (DNA-PK). file:human/PRKDC/PRKDC-uniprot.txt Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage	IBA GO_REF:0000033	KEEP AS NON CORE	Summary: PAINT IBA (node PTN002476708, seeded by mouse Prkdc) for intrinsic apoptotic signalling in response to DNA damage. Reason: DNA-PKcs phosphorylates p53 and contributes to p53 activation after damage, but its role in apoptosis decisions is context-dependent and peripheral to NHEJ. Node placement within the DNA-PKcs clade is accepted; retained as non-core. Supporting Evidence: PMID:22504299 The IFN-γ-dependent poly(ADP-ribosyl)ation of DNA-PKcs (which activates its kinase function) and concomitant activation of the tumor suppressor p53 were specifically prevented by Trp-SA
GO:0016020 membrane	HDA PMID:19946888 Defining the membrane proteome of NK cells.	MARK AS OVER ANNOTATED	Summary: Detected in a membrane proteome of NK-like YTS cells. Reason: DNA-PKcs has no transmembrane segments and is an abundant nuclear protein; detection in a membrane preparation reflects peripheral or contaminating association, as the authors note for many non-integral proteins. A small membrane-associated pool (Feng et al. 2004) does not make membrane a meaningful location. Supporting Evidence: PMID:19946888 The remaining species were largely involved in cellular processes and molecular functions that could be predicted to be transiently associated with membranes.
GO:0016233 telomere capping	IMP PMID:18710952 The catalytic subunit of DNA-dependent protein kinase regula...	KEEP AS NON CORE	Summary: DNA-PKcs-null human cells show telomere defects. Reason: Telomere end protection is a real but secondary role. Supporting Evidence: PMID:18710952 The catalytic subunit of DNA-dependent protein kinase regulates proliferation, telomere length, and genomic stability in human somatic cells. file:human/PRKDC/PRKDC-uniprot.txt Found at the ends of chromosomes, suggesting a further role in the maintenance of telomeric stability and the prevention of chromosomal end fusion
GO:0016301 kinase activity	IEA GO_REF:0000002	MODIFY	Summary: InterPro PI3/4-kinase signature gives kinase activity. Reason: Correct but general; DNA-PKcs is a protein (not lipid) kinase with DNA-dependent Ser/Thr activity. Proposed replacements: DNA-dependent protein kinase activity Supporting Evidence: PMID:7671312 DNA-PK phosphorylates proteins but has no detectable activity toward lipids. file:human/PRKDC/PRKDC-uniprot.txt Belongs to the PI3/PI4-kinase family.
GO:0018105 peptidyl-serine phosphorylation	IDA PMID:15194694 Phosphorylation and regulation of DNA ligase IV stability by...	KEEP AS NON CORE	Summary: DNA-PK phosphorylates Lig4 at Thr650 and possibly Ser668/672. Reason: Process directly executed by DNA-PK kinase activity; peripheral substrate-level detail. Supporting Evidence: PMID:15194694 Using tandem mass spectrometry, we identified a DNA-PK phosphorylation site at Thr-650 in human Lig4
GO:0018105 peptidyl-serine phosphorylation	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	KEEP AS NON CORE	Summary: DNA-PKcs autophosphorylation at serine/threonine clusters. Reason: Process directly executed by DNA-PKcs kinase activity. Supporting Evidence: PMID:32103174 U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609.
GO:0018107 peptidyl-threonine phosphorylation	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	KEEP AS NON CORE	Summary: DNA-PKcs autophosphorylation at the T2609 (threonine) cluster. Reason: Process directly executed by DNA-PKcs kinase activity. Supporting Evidence: PMID:32103174 U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609.
GO:0019899 enzyme binding	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Transferred from mouse Prkdc binding annotations via Ensembl Compara. Reason: Enzyme binding is a near-uninformative binding term; the functionally relevant partner interactions (Ku, Artemis, LIG4) are captured by complex membership and kinase activity. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt DNA-PK is a heterotrimer of PRKDC and the Ku dimer (composed of XRCC6/Ku70 and XRCC5/Ku86)
GO:0019904 protein domain specific binding	IPI PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	MARK AS OVER ANNOTATED	Summary: DNA-PKcs kinase domain is bridged by the WHEP domain of TrpRS (WARS1) to PARP-1. Reason: A single interaction study in an IFN-gamma context; a domain-specific binding term adds little functional information about DNA-PKcs itself. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells.
GO:0031571 mitotic G1 DNA damage checkpoint signaling	IMP PMID:21731742 DNA-PK-dependent RPA2 hyperphosphorylation facilitates DNA r...	MODIFY	Summary: DNA-PK-dependent RPA2 S4/S8 hyperphosphorylation delays mitotic entry after DSBs. Reason: The full text of the cited paper places the effect at the G2/M transition (increased mitotic entry when DNA-PKcs is silenced), not G1. The replacement is the corresponding G2 checkpoint term; this remains a non-core role. Proposed replacements: mitotic G2 DNA damage checkpoint signaling Supporting Evidence: PMID:21731742 DNA-PK-dependent RPA2 phosphorylation at S4, S8 appeared to function in the G2/M checkpoint PMID:21731742 our results demonstrate that RPA2 hyperphosphorylation by DNA-PK in response to DSBs blocks unscheduled homologous recombination and delays mitotic entry.
GO:0032040 small-subunit processome	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	KEEP AS NON CORE	Summary: DNA-PK co-purifies with the small subunit processome. Reason: Non-core rRNA processing role. Supporting Evidence: PMID:32103174 DNA-PK, but not other cNHEJ factors, resides in nucleoli in an rRNA-dependent manner and is co-purified with the small subunit processome. file:human/PRKDC/PRKDC-uniprot.txt As part of the DNA-PK complex, involved in the early steps of ribosome assembly by promoting the processing of precursor rRNA into mature 18S rRNA in the small-subunit processome
GO:0032869 cellular response to insulin stimulus	IMP PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon...	KEEP AS NON CORE	Summary: DNA-PK mediates feeding/insulin-induced USF-1 phosphorylation and FAS activation. Reason: Context-specific signalling role in liver lipogenic gene activation; non-core. Supporting Evidence: PMID:19303849 feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation. PMID:19303849 In DNA-PK-deficient SCID mice, feeding-induced USF-1 phosphorylation/acetylation, DNA breaks, and FAS activation leading to lipogenesis are impaired
GO:0032991 protein-containing complex	IMP PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	TOO GENERAL	Summary: Generic complex membership. Reason: True but uninformative; DNA-PK complex (GO:0070418) and NHEJ complex (GO:0070419) are accepted. Supporting Evidence: PMID:22504299 Here we report a nuclear complex of TrpRS with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) and with poly(ADP-ribose) polymerase 1 (PARP-1), the major PARP in human cells.
GO:0032993 protein-DNA complex	IDA PMID:22504299 Trp-tRNA synthetase bridges DNA-PKcs to PARP-1 to link IFN-γ...	KEEP AS NON CORE	Summary: DNA-PKcs assembles on DNA with Ku as a protein-DNA complex. Reason: The DNA-PK holoenzyme is a protein-DNA complex; retained as non-core because the more informative DNA-PK and NHEJ complex terms carry the core claim. Supporting Evidence: PMID:28840859 In the complex structure, DNA-PKcs, KU70, KU80 and DNA duplex form a 650-kDa heterotetramer with 1:1:1:1 stoichiometry.
GO:0033152 immunoglobulin V(D)J recombination	IBA GO_REF:0000033	ACCEPT	Summary: PAINT IBA for immunoglobulin V(D)J recombination (node PTN002596777, seeded by mouse and zebrafish orthologs). Reason: DNA-PKcs activates Artemis to open RAG-generated coding hairpins and is required for V(D)J joining; DNA-PKcs-deficient humans and mice are SCID. Core function. Supporting Evidence: PMID:11955432 Upon complex formation, DNA-PKcs phosphorylates Artemis, and Artemis acquires endonucleolytic activity on 5' and 3' overhangs, as well as hairpins. PMID:10207111 These DNA-PKcs mutant constructs are able to express the protein but fail to complement the DNA DSB or V(D)J recombination defects of DNA-PKcs mutant cells. file:human/PRKDC/PRKDC-uniprot.txt Promotes processing of hairpin DNA structures in V(D)J recombination by activation of the hairpin endonuclease artemis (DCLRE1C)
GO:0034462 small-subunit processome assembly	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	KEEP AS NON CORE	Summary: U3 snoRNA binding recruits DNA-PK to the small subunit processome. Reason: Non-core rRNA role. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome PMID:32103174 DNA-PK, but not other cNHEJ factors, resides in nucleoli in an rRNA-dependent manner and is co-purified with the small subunit processome.
GO:0034511 U3 snoRNA binding	IDA PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	KEEP AS NON CORE	Summary: Ku-dependent binding of DNA-PKcs to U3 snoRNA activates DNA-PK. Reason: Non-core RNA-binding activity relevant to rRNA processing. Supporting Evidence: PMID:32103174 U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609. file:human/PRKDC/PRKDC-uniprot.txt Binding to U3 small nucleolar RNA, recruits PRKDC and XRCC5/Ku86 to the small-subunit processome
GO:0035979 histone H2AXS139 kinase activity	IDA PMID:14627815 DNA-PK is activated by nucleosomes and phosphorylates H2AX w...	ACCEPT	Summary: DNA-PK phosphorylates H2AX within nucleosomes. Reason: H2AX S139 phosphorylation is a direct DNA-PK activity at DSBs, shared with ATM and ATR. Supporting Evidence: PMID:14627815 Here we show that DNA-PK can be activated by nucleosomes through the ability of Ku to bind to the ends of nucleosomal DNA, and that the activated DNA-PK is capable of phosphorylating H2AX within the nucleosomes. file:human/PRKDC/PRKDC-uniprot.txt Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism
GO:0035979 histone H2AXS139 kinase activity	IDA PMID:16046194 DNA-PK is responsible for enhanced phosphorylation of histon...	ACCEPT	Summary: DNA-PKcs is responsible for enhanced H2AX phosphorylation under hypertonic conditions. Reason: Supports H2AX S139 kinase activity. Supporting Evidence: PMID:16046194 DNA-PKcs deficient M059J cells failed to respond to hypertonic treatment and M059J Fus1 cells corrected for this deficiency showed the expected increase in foci size. file:human/PRKDC/PRKDC-uniprot.txt Phosphorylates 'Ser-139' of histone variant H2AX, thereby regulating DNA damage response mechanism
GO:0036211 protein modification process	TAS PMID:7671312 DNA-dependent protein kinase catalytic subunit: a relative o...	MODIFY	Summary: Hartley et al. cloned DNA-PKcs and showed it phosphorylates proteins. Reason: Correct but general; the specific process is protein phosphorylation (GO:0006468), already carried by the gene. Proposed replacements: protein phosphorylation Supporting Evidence: PMID:7671312 DNA-PK phosphorylates proteins but has no detectable activity toward lipids.
GO:0042752 regulation of circadian rhythm	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Transferred from mouse Prkdc: effect on circadian period through CRY1 stability. Reason: UniProt records this as most likely indirect; there is no evidence that DNA-PKcs acts within the clock mechanism. Over-annotation of a peripheral phenotype. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism
GO:0042752 regulation of circadian rhythm	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Transferred from mouse Prkdc: effect on circadian period through CRY1 stability. Reason: UniProt records this as most likely indirect; there is no evidence that DNA-PKcs acts within the clock mechanism. Over-annotation of a peripheral phenotype. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Contributes to the determination of the circadian period length by antagonizing phosphorylation of CRY1 'Ser-588' and increasing CRY1 protein stability, most likely through an indirect mechanism
GO:0043066 negative regulation of apoptotic process	IMP PMID:24485452 DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3.	KEEP AS NON CORE	Summary: Depletion of DNA-PK reduces survival after DNA damage (Golgi dispersal pathway). Reason: Context-specific pro-survival role after DNA damage; non-core. Supporting Evidence: PMID:24485452 Interference with the Golgi DNA damage response by depletion of DNA-PK, GOLPH3, or MYO18A reduces survival after DNA damage
GO:0045621 positive regulation of lymphocyte differentiation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of lymphocyte differentiation. Reason: Lymphocyte development depends on V(D)J recombination, in which DNA-PKcs acts; loss of lymphocytes in SCID is a downstream consequence, not regulation of differentiation by DNA-PKcs. V(D)J recombination is annotated separately. Supporting Evidence: PMID:18710952 DNA-PK functions in the nonhomologous end-joining pathway for the repair of DNA double-stranded breaks (DSBs) introduced by either exogenous DNA damage or endogenous processes, such as lymphoid V(D)J recombination. file:human/PRKDC/PRKDC-uniprot.txt Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination
GO:0045621 positive regulation of lymphocyte differentiation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of lymphocyte differentiation. Reason: Lymphocyte development depends on V(D)J recombination, in which DNA-PKcs acts; loss of lymphocytes in SCID is a downstream consequence, not regulation of differentiation by DNA-PKcs. V(D)J recombination is annotated separately. Supporting Evidence: PMID:18710952 DNA-PK functions in the nonhomologous end-joining pathway for the repair of DNA double-stranded breaks (DSBs) introduced by either exogenous DNA damage or endogenous processes, such as lymphoid V(D)J recombination. file:human/PRKDC/PRKDC-uniprot.txt Involved in DNA non-homologous end joining (NHEJ) required for double-strand break (DSB) repair and V(D)J recombination
GO:0045648 positive regulation of erythrocyte differentiation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of erythrocyte differentiation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:0045648 positive regulation of erythrocyte differentiation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of erythrocyte differentiation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:0045727 positive regulation of translation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of translation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:0045727 positive regulation of translation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of translation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon...	KEEP AS NON CORE	Summary: DNA-PK-dependent USF-1 phosphorylation activates FAS transcription. Reason: Context-specific transcriptional coactivation; non-core. Supporting Evidence: PMID:19303849 feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation. PMID:19303849 In DNA-PK-deficient SCID mice, feeding-induced USF-1 phosphorylation/acetylation, DNA breaks, and FAS activation leading to lipogenesis are impaired
GO:0048660 regulation of smooth muscle cell proliferation	IMP PMID:25852083 DNA-dependent protein kinase (DNA-PK) permits vascular smoot...	KEEP AS NON CORE	Summary: DNA-PK phosphorylates and stabilizes NOR1, permitting vascular SMC proliferation. Reason: Context-specific signalling role; non-core. Supporting Evidence: PMID:25852083 DNA-PK directly phosphorylates NOR-1 and, this way, modulates SMC proliferation.
GO:0050678 regulation of epithelial cell proliferation	IMP PMID:18710952 The catalytic subunit of DNA-dependent protein kinase regula...	MARK AS OVER ANNOTATED	Summary: Proliferation defect of DNA-PKcs-null HCT116 cells. Reason: The proliferation deficit accompanies genomic instability in knockout cells and is an indirect consequence, not a regulatory function of DNA-PKcs in epithelial proliferation. Supporting Evidence: PMID:18710952 the cell line lacking this gene has profound proliferation and genomic stability deficits not observed for other mammalian systems.
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding	IPI PMID:19303849 A role of DNA-PK for the metabolic gene regulation in respon...	KEEP AS NON CORE	Summary: DNA-PK binds USF-1 at the FAS promoter. Reason: Binding of a sequence-specific transcription factor that DNA-PK phosphorylates; non-core. Supporting Evidence: PMID:19303849 feeding induces the recruitment of DNA-PK to USF-1 and its phosphorylation, which then allows recruitment of P/CAF, resulting in USF-1 acetylation and FAS promoter activation.
GO:0070418 DNA-dependent protein kinase complex	IPI PMID:28840859 Cryo-EM structure of human DNA-PK holoenzyme.	ACCEPT	Summary: Cryo-EM of DNA-PK holoenzyme (DNA-PKcs, Ku70, Ku80, DNA). Reason: Core complex membership. Supporting Evidence: PMID:28840859 In the complex structure, DNA-PKcs, KU70, KU80 and DNA duplex form a 650-kDa heterotetramer with 1:1:1:1 stoichiometry.
GO:0070419 nonhomologous end joining complex	IDA PMID:20383123 Ku is a 5'-dRP/AP lyase that excises nucleotide damage near ...	ACCEPT	Summary: Purified NHEJ core factors including DNA-PKcs. Reason: Core NHEJ complex membership. Supporting Evidence: PMID:20383123 purified human NHEJ core factors (Ku, DNA-PKcs, XLF/Cernunnos, and XRCC4-LigaseIV) file:human/PRKDC/PRKDC-uniprot.txt Component of the core long-range non-homologous end joining (NHEJ) complex (also named DNA-PK complex) composed of PRKDC, LIG4, XRCC4, XRCC6/Ku70, XRCC5/Ku86 and NHEJ1/XLF
GO:0070419 nonhomologous end joining complex	IDA PMID:25941166 XLS (c9orf142) is a new component of mammalian DNA double-st...	ACCEPT	Summary: DNA-PKcs co-purifies with all core NHEJ factors. Reason: Core NHEJ complex membership. Supporting Evidence: PMID:25941166 Here we show using combined affinity purification and mass spectrometry that DNA-PKcs co-purifies with all known core NHEJ factors.
GO:0080135 regulation of cellular response to stress	IEA GO_REF:0000117	MARK AS OVER ANNOTATED	Summary: ARBA machine-learning annotation. Reason: Vague regulatory term; DNA-PKcs functions are captured by NHEJ, DNA damage response and specific signalling terms. Supporting Evidence: file:human/PRKDC/PRKDC-uniprot.txt Serine/threonine-protein kinase that acts as a molecular sensor for DNA damage
GO:0097681 double-strand break repair via alternative nonhomologous end joining	TAS PMID:18710952 The catalytic subunit of DNA-dependent protein kinase regula...	REMOVE	Summary: Author statement linking DNA-PKcs to alternative NHEJ. Reason: By GO definition, alternative NHEJ is independent of factors important for V(D)J recombination, and DNA-PKcs is one of those classical NHEJ factors. DNA-PKcs acts in classical NHEJ (GO:0006303, accepted). Alt-EJ activity observed in DNA-PKcs-deficient cells would not make DNA-PKcs a participant. Supporting Evidence: PMID:18710952 DNA-PK functions in the nonhomologous end-joining pathway for the repair of DNA double-stranded breaks (DSBs) introduced by either exogenous DNA damage or endogenous processes, such as lymphoid V(D)J recombination. PMID:10207111 These DNA-PKcs mutant constructs are able to express the protein but fail to complement the DNA DSB or V(D)J recombination defects of DNA-PKcs mutant cells.
GO:0106310 protein serine kinase activity	EXP PMID:15262962 Identification of a PKB/Akt hydrophobic motif Ser-473 kinase...	ACCEPT	Summary: Serine phosphorylation by DNA-PK. Reason: Direct experimental support for protein serine kinase activity, a facet of the core catalytic activity. Supporting Evidence: PMID:15262962 In vitro, DNA-PK phosphorylated PKB on Ser-473, resulting in a approximately 10-fold enhancement of PKB activity.
GO:0106310 protein serine kinase activity	EXP PMID:29478807 The Histone Chaperones ASF1 and CAF-1 Promote MMS22L-TONSL-M...	ACCEPT	Summary: Serine phosphorylation by DNA-PK. Reason: Direct experimental support for protein serine kinase activity, a facet of the core catalytic activity. Supporting Evidence: PMID:29478807 ASF1A is phosphorylated on serine 192 in a manner dependent on DNA-PKcs in response to DSBs
GO:0106310 protein serine kinase activity	EXP PMID:32103174 DNA-PKcs has KU-dependent function in rRNA processing and ha...	ACCEPT	Summary: Serine phosphorylation by DNA-PK. Reason: Direct experimental support for protein serine kinase activity, a facet of the core catalytic activity. Supporting Evidence: PMID:32103174 U3 activates purified DNA-PK and triggers phosphorylation of DNA-PKcs at T2609.
GO:0106310 protein serine kinase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea-based protein serine kinase activity. Reason: Consistent with curated catalytic activity. Supporting Evidence: PMID:15262962 In vitro, DNA-PK phosphorylated PKB on Ser-473, resulting in a approximately 10-fold enhancement of PKB activity.
GO:0160049 negative regulation of cGAS/STING signaling pathway	IDA PMID:33273464 DNA-PK deficiency potentiates cGAS-mediated antiviral innate...	KEEP AS NON CORE	Summary: DNA-PK phosphorylates cGAS and suppresses cGAMP synthesis. Reason: Direct mechanism (cGAS phosphorylation) with genetic and patient-cell support; an immune-regulatory role that is non-core relative to NHEJ. Supporting Evidence: PMID:33273464 we report that DNA-PK phosphorylates cGAS and suppresses its enzymatic activity. PMID:35460603 Activated DNA-PK phosphorylates PARP1 on Thr594, thus facilitating the cytoplasmic translocation of PARP1 to inhibit the antiviral immunity both in vitro and in vivo.
GO:1902036 regulation of hematopoietic stem cell differentiation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of regulation of hematopoietic stem cell differentiation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:1902036 regulation of hematopoietic stem cell differentiation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of regulation of hematopoietic stem cell differentiation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:1905221 positive regulation of platelet formation	IEA GO_REF:0000107	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of platelet formation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:1905221 positive regulation of platelet formation	ISS GO_REF:0000024	MARK AS OVER ANNOTATED	Summary: Mouse-to-human transfer of positive regulation of platelet formation. Reason: Derived from mouse DNA-PKcs mutants with bone marrow failure and reduced protein synthesis, which Shao et al. attribute to defective 18S rRNA processing. These haematopoietic and translational phenotypes are downstream consequences of the ribosome-biogenesis role (annotated separately), not regulation of these processes by DNA-PKcs. Supporting Evidence: PMID:32103174 Blocking the phosphorylation of DNA-PKcs at the T2609 cluster, but not the S2056 cluster, led to KU-dependent defects in 18S rRNA processing, compromised global protein synthesis in haematopoietic cells and caused bone marrow failure in mice.
GO:2001034 positive regulation of double-strand break repair via nonhomologous end joining	IDA PMID:26237645 Local generation of fumarate promotes DNA repair through inh...	KEEP AS NON CORE	Summary: DNA-PK phosphorylation of FH promotes local fumarate production and further DNA-PK accumulation at DSBs. Reason: A feed-forward loop in which DNA-PK enhances its own NHEJ function; DNA-PKcs is primarily a direct NHEJ participant (GO:0006303), so the regulatory term is non-core. Supporting Evidence: PMID:26237645 this increases the accumulation of the Ku70-containing DNA-PK at DSB regions for non-homologous end-joining DNA repair and cell survival.
GO:0035861 site of double-strand break	IDA PMID:12231622 Autophosphorylation of the DNA-dependent protein kinase cata...	NEW	Summary: Autophosphorylated DNA-PKcs (pT2609) forms foci that colocalize with gamma-H2AX and 53BP1 at DSBs. Reason: DNA-PKcs is recruited by Ku to DNA ends at DSBs, where it performs its NHEJ function; this location is not otherwise captured (only nucleus/nucleoplasm/chromatin). Comparator check (QuickGO, Oct 2026): other NHEJ/DSB factors XRCC4, NHEJ1/XLF, PAXX, TP53BP1 and ATM carry this term by IDA, while XRCC5, XRCC6 and LIG4 do not, so its absence for PRKDC is not a systematic convention. A cellular component, so the process participation test does not apply. Supporting Evidence: PMID:12231622 Phosphorylated DNA-PKcs colocalizes with both gamma-H2AX and 53BP1 after DNA damage. Reactome:R-HSA-5693571 The catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs, PRKDC) is then recruited to DNA-bound Ku to form the DNA-PK holoenzyme.

Gene Description

Existing Annotations Review

Core Functions

DNA end-activated serine/threonine protein kinase of the DNA-PK holoenzyme. Recruited by Ku to DNA double-strand break ends, DNA-PKcs protects and synapses the ends with XRCC4-LIG4-XLF and autophosphorylates in trans to allow end processing and ligation in classical non-homologous end joining.

In V(D)J recombination, DNA-PKcs forms a complex with Artemis and phosphorylates it, activating the Artemis endonuclease that opens RAG-generated coding-end hairpins; human PRKDC mutations cause radiosensitive SCID.

DNA damage signalling kinase at double-strand breaks, phosphorylating chromatin and repair substrates including histone H2AX Ser139 alongside ATM and ATR.

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