Binding of inositol hexakisphosphate (IP6) to Ku but not to DNA-PKcs.
The nonhomologous DNA end joining (NHEJ) pathway is responsible for repairing a major fraction of double strand DNA breaks in somatic cells of all multicellular eukaryotes. As an indispensable protein in the NHEJ pathway, Ku has been hypothesized to be the first protein to bind at the DNA ends generated at a double strand break being repaired by this pathway. When bound to a DNA end, Ku improves the affinity of another DNA end-binding protein, DNA-PK(cs), to that end. The Ku.DNA-PK(cs) complex is often termed the DNA-PK holoenzyme. It was recently shown that myo-inositol hexakisphosphate (IP(6)) stimulates the joining of complementary DNA ends in a cell free system. Moreover, the binding data suggested that IP(6) bound to DNA-PK(cs) (not to Ku). Here we clearly show that, in fact, IP(6) associates not with DNA-PK(cs), but rather with Ku. Furthermore, the binding of DNA ends and IP(6) to Ku are independent of each other. The possible relationship between inositol phosphate metabolism and DNA repair is discussed in light of these findings.
Ma
Yunmei
Y
Norris Comprehensive Cancer Center, Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, California 90089-9176, USA.
Lieber
Michael R
MR
D034961:Antigens, Nuclear; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002474:Cell-Free System; D004265:DNA Helicases; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D006367:HeLa Cells; D006801:Humans; D000072200:Ku Autoantigen; D009687:Nuclear Proteins / Q000378:metabolism*; D010833:Phytic Acid / Q000378:metabolism*; D011485:Protein Binding; D020349:Surface Plasmon Resonance
D034961:Antigens, Nuclear; C109198:CIB1 protein, human; D002135:Calcium-Binding Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D010833:Phytic Acid; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen