REGULATION OF DNA-DEPENDENT PROTEIN-KINASE BY THE LYN TYROSINE KINASE

The Src-like protein-tyrosine kinase Lyn is activated by ionizing radi ation and certain other DNA-damaging agents, whereas the DNA-dependent protein kinase (DNA-PK), consisting of the catalytic subunits (DNA-PK cs) and Ku DNA-binding components, requires DNA double-stranded breaks for activation. Here me demonstrate that Lyn associates constitutivel y with DNA-PKcs. The SH3 domain of Lyn interacts directly with DNA-PKc s near a leucine zipper homology domain. We also show that Lyn phospho rylates DNA-PKcs but not Ku in vitro. The interaction between Lyn and DNA-PKcs inhibits DNA-PKcs activity and the ability of DNA-PKcs to for m a complex with Ku/DNA. These results support the hypothesis that the re are functional interactions between Lyn and DNA-PKcs in the respons e to DNA damage.