title: N-terminal constraint activates the catalytic subunit of the DNA-dependent protein kinase in the absence of DNA or Ku.
abstract: The DNA-dependent protein kinase (DNA-PK) was identified as an activity and as its three component polypeptides 25 and 15 years ago, respectively. It has been exhaustively characterized as being absolutely dependent on free double stranded DNA ends (to which it is directed by its regulatory subunit, Ku) for its activation as a robust nuclear serine/threonine protein kinase. Here, we report the unexpected finding of robust DNA-PKcs activation by N-terminal constraint, independent of either DNA or its regulatory subunit Ku. These data suggest that an N-terminal conformational change (likely induced by DNA binding) induces enzymatic activation.
authors.affiliation: Department of Microbiology and Molecular Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. kmeek@msu.edu
authors.forename: Katheryn
authors.initials: K
authors.lastname: Meek
authors.forename: Susan P
authors.initials: SP
authors.lastname: Lees-Miller
authors.forename: Mauro
authors.initials: M
authors.lastname: Modesti
mesh_terms: D000818:Animals; D034961:Antigens, Nuclear / Q000502:physiology; D016466:CHO Cells; D020134:Catalytic Domain; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000378:metabolism*; D051747:DNA-Activated Protein Kinase / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D000072200:Ku Autoantigen; D010766:Phosphorylation; D012965:Sodium Chloride / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; D012965:Sodium Chloride; D004247:DNA; D051747:DNA-Activated Protein Kinase; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen