Multi-functions of DNA-dependent protein kinase (DNA-PK) and the association of radiation sensitivity

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Severe combined immunodeficient (scid) mice are aberrant in DSB repair and are thus sensitive to ionizing radiation. An underlying gene for murine scid was mapped in human chromosome 8q11 by Komatsu and identified as a catalytic subunit of DNA-dependent protein kinase (DNA-PK). The DNA-PK complex such as Ku70, Ku80, and DNA-PKcs, could play a critical role in rejoining radiation-induced dsb and signal transduction following DNA damage, but the mechanism remains unclear. Recently, scid mice also show predisposed to thymic lymphoma. In this study, we demonstrated the multi-function of DNA-PK using in vitron and in vivo assay system. (1) the coding joint formation is aberrant in scid mutation but signal joint formation is normal. Moreover, (2) Ku80 is labile for heat at 43ﾟC and it could cause the hyperthermic sensitization of radiation-induced cell killing. On the other hand, (3) DNA-PK (scid mutation) contributes to the genomic instability on the basis of Pc-1 micro-satellite. Finally, (4) our results showed the involvement of DNA-PK in mouse embryogenesis, where the radiation-induced teralogenesis in scid mice is significently high than that of control mice.