scholarly journals Microarray analysis of the DNA-dependent protein kinase catalytic subunit knock-out mouse: global effects on gene regulation and the cellular response to ionizing radiation

10.1038/14277 ◽  
1999 ◽  
Vol 23 (S3) ◽  
pp. 36-36
Author(s):  
Robert B. Cary ◽  
Akihiro Kurimasa ◽  
Konan Peck ◽  
David J. Chen
Keyword(s):  
Gene Regulation ◽  
Protein Kinase ◽  
Ionizing Radiation ◽  
Microarray Analysis ◽  
Cellular Response ◽  
Catalytic Subunit ◽  
Dependent Protein Kinase ◽  
Knock Out ◽  
Dependent Protein ◽  
Knock Out Mouse

scholarly journals ATR-Dependent Phosphorylation of DNA-Dependent Protein Kinase Catalytic Subunit in Response to UV-Induced Replication Stress

2006 ◽  
Vol 26 (20) ◽  
pp. 7520-7528 ◽  
Author(s):  
Hirohiko Yajima ◽  
Kyung-Jong Lee ◽  
Benjamin P. C. Chen
Keyword(s):  
Protein Kinase ◽  
Uv Irradiation ◽  
Cellular Response ◽  
Replication Stress ◽  
Dominant Negative ◽  
Catalytic Subunit ◽  
Dependent Manner ◽  
Dependent Protein Kinase ◽  
Dependent Protein

ABSTRACT Phosphorylation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) upon ionizing radiation (IR) is essential for cellular radioresistance and nonhomologous-end-joining-mediated DNA double-strand break repair. In addition to IR induction, we have previously shown that DNA-PKcs phosphorylation is increased upon camptothecin treatment, which induces replication stress and replication-associated double-strand breaks. To clarify the involvement of DNA-PKcs in this process, we analyzed DNA-PKcs phosphorylation in response to UV irradiation, which causes replication stress and activates ATR (ATM-Rad3-related)/ATM (ataxia-telangiectasia mutated) kinases in a replication-dependent manner. Upon UV irradiation, we observed a rapid DNA-PKcs phosphorylation at T2609 and T2647, but not at S2056, distinct from that induced by IR. UV-induced DNA-PKcs phosphorylation occurs specifically only in replicating cells and is dependent on ATR kinase. Inhibition of ATR activity via caffeine, a dominant-negative kinase-dead mutant, or RNA interference led to the attenuation of UV-induced DNA-PKcs phosphorylation. Furthermore, DNA-PKcs associates with ATR in vivo and is phosphorylated by ATR in vitro, suggesting that DNA-PKcs could be the direct downstream target of ATR. Taken together, these results strongly suggest that DNA-PKcs is required for the cellular response to replication stress and might play an important role in the repair of stalled replication forks.

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