Ku protein stimulates DNA end joining by mammalian DNA ligases: a direct role for Ku in repair of DNA double-strand breaks.
Ku protein binds to DNA ends and is a cofactor for the DNA-dependent protein kinase. Both of these components are involved in DNA double-strand break repair, but it has not been clear if they function indirectly, by sensing DNA damage and activating other factors, or if they are more directly involved in the processing and rejoining of DNA breaks. We demonstrate that intermolecular ligation of DNA fragments is highly dependent on Ku under conditions designed to mimic those existing in the cell. This effect of Ku is specific to eukaryotic DNA ligases. Ku protein, therefore, has an activity consistent with a direct role in rejoining DNA breaks and independent of DNA-dependent protein kinase.
Ramsden
D A
DA
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892-0540, USA.
Gellert
M
M
D034961:Antigens, Nuclear; D004247:DNA / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000378:metabolism / Q000502:physiology*; D004260:DNA Repair / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000502:physiology*; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins
D034961:Antigens, Nuclear; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D029867:Xenopus Proteins; D004247:DNA; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D011088:DNA Ligases; D000072481:DNA Ligase ATP; C000618816:DNA ligase III alpha protein, Xenopus