scholarly journals DNA-Dependent protein kinase in DNA damage response: Three decades and beyond

2020 ◽  
Vol 11 (4) ◽  
pp. 123
Author(s):  
Yoshihisa Matsumoto ◽  
MukeshKumar Sharma
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Dependent Protein Kinase ◽  
Damage Response ◽  
Dependent Protein

scholarly journals Nuclear localized Raf1 isoform alters DNA‐dependent protein kinase activity and the DNA damage response

2018 ◽  
Vol 33 (1) ◽  
pp. 1138-1150 ◽  
Author(s):  
Benjamin R. Nixon ◽  
Sara C. Sebag ◽  
Michael S. Glennon ◽  
Eric J. Hall ◽  
Emily S. Kounlavong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Dependent Protein Kinase ◽  
Damage Response ◽  
Dependent Protein

scholarly journals HTLV-1 Tax Oncoprotein Subverts the Cellular DNA Damage Response via Binding to DNA-dependent Protein Kinase

2008 ◽  
Vol 283 (52) ◽  
pp. 36311-36320 ◽  
Author(s):  
Sarah S. Durkin ◽  
Xin Guo ◽  
Kimberly A. Fryrear ◽  
Valia T. Mihaylova ◽  
Saurabh K. Gupta ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Dependent Protein Kinase ◽  
Damage Response ◽  
Dependent Protein ◽  
Cellular Dna

scholarly journals Adeno-Associated Virus Replication Induces a DNA Damage Response Coordinated by DNA-Dependent Protein Kinase

2009 ◽  
Vol 83 (12) ◽  
pp. 6269-6278 ◽  
Author(s):  
Rachel A. Schwartz ◽  
Christian T. Carson ◽  
Christine Schuberth ◽  
Matthew D. Weitzman
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Dependent Protein Kinase ◽  
Adeno Associated Virus ◽  
Host Cell Response ◽  
Rep Proteins ◽  
Damage Response ◽  
Dependent Protein ◽  
Cellular Replication

ABSTRACT The parvovirus adeno-associated virus (AAV) contains a small single-stranded DNA genome with inverted terminal repeats that form hairpin structures. In order to propagate, AAV relies on the cellular replication machinery together with functions supplied by coinfecting helper viruses such as adenovirus (Ad). Here, we examined the host cell response to AAV replication in the context of Ad or Ad helper proteins. We show that AAV and Ad coinfection activates a DNA damage response (DDR) that is distinct from that seen during Ad or AAV infection alone. The DDR was also triggered when AAV replicated in the presence of minimal Ad helper proteins. We detected autophosphorylation of the kinases ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and signaling to downstream targets SMC1, Chk1, Chk2, H2AX, and XRCC4 and multiple sites on RPA32. The Mre11 complex was not required for activation of the DDR to AAV infection. Additionally, we found that DNA-PKcs was the primary mediator of damage signaling in response to AAV replication. Immunofluorescence revealed that some activated damage proteins were found in a pan-nuclear pattern (phosphorylated ATM, SMC1, and H2AX), while others such as DNA-PK components (DNA-PKcs, Ku70, and Ku86) and RPA32 accumulated at AAV replication centers. Although expression of the large viral Rep proteins contributed to some damage signaling, we observed that the full response required replication of the AAV genome. Our results demonstrate that AAV replication in the presence of Ad helper functions elicits a unique damage response controlled by DNA-PK.

Effects of the novel DNA dependent protein kinase inhibitor, IC486241, on the DNA damage response to doxorubicin and cisplatin in breast cancer cells

2011 ◽  
Vol 30 (4) ◽  
pp. 1736-1742 ◽  
Author(s):  
David Davidson ◽  
Jeremy Grenier ◽  
Veronica Martinez-Marignac ◽  
Lilian Amrein ◽  
May Shawi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Breast Cancer Cells ◽  
Kinase Inhibitor ◽  
The Novel ◽  
Dependent Protein Kinase ◽  
Damage Response ◽  
Dependent Protein

scholarly journals Steroidogenic Factor 1 (NR5A1) Maintains Centrosome Homeostasis in Steroidogenic Cells by Restricting Centrosomal DNA-Dependent Protein Kinase Activation

2012 ◽  
Vol 33 (3) ◽  
pp. 476-484 ◽  
Author(s):  
Chia-Yih Wang ◽  
Yung-Hsin Kao ◽  
Pao-Yen Lai ◽  
Wei-Yi Chen ◽  
Bon-chu Chung
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Nuclear Dna ◽  
Cyclin A ◽  
Dependent Protein Kinase ◽  
Steroidogenic Factor 1 ◽  
Damage Response ◽  
Dependent Protein ◽  
Steroidogenic Cells

ABSTRACTSteroidogenic factor 1 (SF-1 or NR5A1) is a nuclear receptor that controls adrenogenital cell growth and differentiation. Adrenogenital primordial cells fromSF-1knockout mice die of apoptosis, but the mechanism by which SF-1 regulates cell survival is not entirely clear. Besides functioning in the nucleus, SF-1 also resides in the centrosome and controls centrosome homeostasis. Here, we show that SF-1 restricts centrosome overduplication by inhibiting aberrant activation of DNA-dependent protein kinase (DNA-PK) in the centrosome. SF-1 was found to be associated with Ku70/Ku80 only in the centrosome, sequestering them from the catalytic subunit of DNA-PK (DNA-PKcs). In the absence of SF-1, DNA-PKcs was recruited to the centrosome and activated, causing aberrant activation of centrosomal Akt and cyclin-dependent kinase 2 (CDK2)/cyclin A and leading to centrosome overduplication. Centrosome overduplication caused by SF-1 depletion was averted by the elimination of DNA-PKcs, Ku70/80, or cyclin A or by the inhibition of CDK2 or Akt. In the nucleus, SF-1 did not interact with Ku70/80, and SF-1 depletion did not activate a nuclear DNA damage response. Centriole biogenesis was also unaffected. Thus, centrosomal DNA-PK signaling triggers centrosome overduplication, and this centrosomal event, but not the nuclear DNA damage response, is controlled by SF-1.

scholarly journals The DNA Damage Response Kinases DNA-dependent Protein Kinase (DNA-PK) and Ataxia Telangiectasia Mutated (ATM) Are Stimulated by Bulky Adduct-containing DNA

2011 ◽  
Vol 286 (22) ◽  
pp. 19237-19246 ◽  
Author(s):  
Michael G. Kemp ◽  
Laura A. Lindsey-Boltz ◽  
Aziz Sancar
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Dna Adducts ◽  
Ataxia Telangiectasia ◽  
Ataxia Telangiectasia Mutated ◽  
Dependent Protein Kinase ◽  
Damage Response ◽  
Dependent Protein ◽  
Bulky Dna Adducts

A variety of environmental, carcinogenic, and chemotherapeutic agents form bulky lesions on DNA that activate DNA damage checkpoint signaling pathways in human cells. To identify the mechanisms by which bulky DNA adducts induce damage signaling, we developed an in vitro assay using mammalian cell nuclear extract and plasmid DNA containing bulky adducts formed by N-acetoxy-2-acetylaminofluorene or benzo(a)pyrene diol epoxide. Using this cell-free system together with a variety of pharmacological, genetic, and biochemical approaches, we identified the DNA damage response kinases DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) as bulky DNA damage-stimulated kinases that phosphorylate physiologically important residues on the checkpoint proteins p53, Chk1, and RPA. Consistent with these results, purified DNA-PK and ATM were directly stimulated by bulky adduct-containing DNA and preferentially associated with damaged DNA in vitro. Because the DNA damage response kinase ATM and Rad3-related (ATR) is also stimulated by bulky DNA adducts, we conclude that a common biochemical mechanism exists for activation of DNA-PK, ATM, and ATR by bulky adduct-containing DNA.

scholarly journals In VivoAnalysis of Protein Kinase B (PKB)/Akt Regulation in DNA-PKcs-null Mice Reveals a Role for PKB/Akt in DNA Damage Response and Tumorigenesis

2008 ◽  
Vol 283 (44) ◽  
pp. 30025-30033 ◽  
Author(s):  
Banu Surucu ◽  
Lana Bozulic ◽  
Debby Hynx ◽  
Arnaud Parcellier ◽  
Brian A. Hemmings
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Protein Kinase B ◽  
Damage Response

scholarly journals Beyond ATM: The protein kinase landscape of the DNA damage response

FEBS Letters ◽  
2011 ◽  
Vol 585 (11) ◽  
pp. 1625-1639 ◽  
Author(s):  
Ariel Bensimon ◽  
Ruedi Aebersold ◽  
Yosef Shiloh
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Damage Response
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