Abstract
Ionizing radiation induces various damages on genomic DNA. Among those, DNA double strand breaks (DSBs) are the most critical damage and it might be a main cause of cell killing in cancer radiotherapy. There are at least two pathways for DSBs, one is non-homologous end joining (NHEJ) and the other is homologous recombination (HR). We report here that the partial inhibition of the HR pathways has significant potential for application for improvement of cancer radiotherapy through the slight but enough radio-sensitization. A specific, strong inhibitor of any HR protein should be an effective radio-sensitizer because it shut down the S/G2 specific DSB repair pathway. However, this efficient inhibition of HR results a strong cytotoxicity, in other words, the inhibitor cannot reach the bed side, due to its strong side effects. Our novel concept is that inhibiting the function of a specific domain of a DSB repair protein can partially suppress HR pathway and reduce cancer cell viability following irradiation with slight but enough efficiency. This weak radio-sensitization can be enhanced if radiation is given with a sprit dose because the recovery from sublethal damage depends on HR.
