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SUMMARY:DNA-dependent protein kinase is a DNA sensor for IRF-3-dependent i
 nnate immunity - Geoffrey Smith\, Department of Pathology Cambridge
DTSTART:20111006T151500Z
DTEND:20111006T170000Z
UID:TALK32573@talks.cam.ac.uk
CONTACT:Scientific Meetings Co-ordinator
DESCRIPTION:Nucleic acids are a key target for the innate immune response 
 to pathogens and\, while the mechanisms of RNA sensing are well establishe
 d\, receptors for DNA have only recently been discovered. Here we show tha
 t the DNA-dependent protein kinase (DNA-PK) acts as an intracellular DNA s
 ensor. DNA-PK bound to DNA in the cytoplasm and the absence of Ku or DNA-P
 Kcs resulted in impaired transcription of type I interferon (IFN)\, cytoki
 ne and chemokine genes following DNA stimulation. DNA-PK binds IFN regulat
 ory factor 3 (IRF-3) and is required to initiate IRF-3-dependent signallin
 g in response to DNA via a pathway involving TANK binding kinase 1 (TBK1) 
 and stimulator of interferon genes (STING). The importance of this pathway
  in sensing virus infection is shown by the observations that in cells inf
 ected with modified vaccinia Ankara (MVA) Ku70 and DNA-PKcs are associated
  with sites of viral DNA replication\, and MVA infection of cells lacking 
 DNA-PK components induced attenuated cytokine responses and increased viru
 s protein expression. DNA-PK has a long-established role in DNA double-str
 and break repair in the nucleus and its loss causes a severe combined immu
 ne deficiency (SCID) phenotype\, but here we describe a novel anti-microbi
 al function for this complex. 
LOCATION:Max Perutz Lecture Theatre\, Medical Research Council (MRC) (MRC 
 Laboratory of Molecular Biol
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