scholarly journals The DNA damage response in DNA-dependent protein kinase-deficient SCID mouse cells: Replication protein A hyperphosphorylation and p53 induction

1996 ◽  
Vol 93 (24) ◽  
pp. 13825-13830 ◽  
Author(s):  
L. M. Fried ◽  
C. Koumenis ◽  
S. R. Peterson ◽  
S. L. Green ◽  
P. van Zijl ◽  
...  
Keyword(s):  
Dna Damage ◽  
Protein Kinase ◽  
Dna Damage Response ◽  
Scid Mouse ◽  
Protein A ◽  
Replication Protein A ◽  
Dependent Protein Kinase ◽  
Damage Response ◽  
Dependent Protein ◽  
Mouse Cells

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 Roles of Replication Protein A and DNA-dependent Protein Kinase in the Regulation of DNA Replication following DNA Damage

1999 ◽  
Vol 274 (31) ◽  
pp. 22060-22064 ◽  
Author(s):  
Ya Wang ◽  
Xiang-Yang Zhou ◽  
Hongyan Wang ◽  
M. Saiful Huq ◽  
George Iliakis
Keyword(s):  
Dna Damage ◽  
Dna Replication ◽  
Protein Kinase ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Dependent Protein Kinase ◽  
Dependent Protein

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 Single-stranded-DNA binding alters human replication protein A structure and facilitates interaction with DNA-dependent protein kinase.

1996 ◽  
Vol 16 (9) ◽  
pp. 4798-4807 ◽  
Author(s):  
L J Blackwell ◽  
J A Borowiec ◽  
I A Mastrangelo
Keyword(s):  
Protein Kinase ◽  
Dna Binding ◽  
Protein A ◽  
Replication Protein A ◽  
Replication Protein ◽  
Physical Interaction ◽  
Binding Modes ◽  
Dependent Protein Kinase ◽  
Single Stranded Dna ◽  
Dependent Protein

Human replication protein A (hRPA) is an essential single-stranded-DNA-binding protein that stimulates the activities of multiple DNA replication and repair proteins through physical interaction. To understand DNA binding and its role in hRPA heterologous interaction, we examined the physical structure of hRPA complexes with single-stranded DNA (ssDNA) by scanning transmission electron microscopy. Recent biochemical studies have shown that hRPA combines with ssDNA in at least two binding modes: by interacting with 8 to 10 nucleotides (hRPA8nt) and with 30 nucleotides (hRPA30nt). We find the relatively unstable hRPA8nt complex to be notably compact with many contacts between hRPA molecules. In contrast, on similar lengths of ssDNA, hRPA30nt complexes align along the DNA and make few intermolecular contacts. Surprisingly, the elongated hRPA30nt complex exists in either a contracted or an extended form that depends on ssDNA length. Therefore, homologous-protein interaction and available ssDNA length both contribute to the physical changes that occur in hRPA when it binds ssDNA. We used activated DNA-dependent protein kinase as a biochemical probe to detect alterations in conformation and demonstrated that formation of the extended hRPA30nt complex correlates with increased phosphorylation of the hRPA 29-kDa subunit. Our results indicate that hRPA binds ssDNA in a multistep pathway, inducing new hRPA alignments and conformations that can modulate the functional interaction of other factors with hRPA.

scholarly journals Simian Virus Large T Antigen Interacts with the N-Terminal Domain of the 70 kD Subunit of Replication Protein A in the Same Mode as Multiple DNA Damage Response Factors

PLoS ONE ◽  
2015 ◽  
Vol 10 (2) ◽  
pp. e0116093 ◽  
Author(s):  
Boting Ning ◽  
Michael D. Feldkamp ◽  
David Cortez ◽  
Walter J. Chazin ◽  
Katherine L. Friedman ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Protein A ◽  
Replication Protein A ◽  
Simian Virus ◽  
T Antigen ◽  
Replication Protein ◽  
Large T Antigen ◽  
Response Factors ◽  
Damage Response
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