Abstract
Ionizing radiation efficiently induces DNA double strand breaks (DSBs). There are two major pathways to repair those DSBs. One is homologous recombination (HR) and the other is non-homologous end joining (NHEJ). HR is thought to occur during late-S and G2 phase of cell cycle because it requires sister chromatid as a repair template. NBS1, a component of MRN (MRE11/RAD50/NBS1) complex plays a crucial role in HR. We investigated whether the partial inhibition of NBS1 could affect HR efficiency or not. A mutant form of NBS1 was constructed and was introduced into HeLa or MRC5 cells. Expression of the mutant NBS1 resulted partial inhibition of radiation induced foci formation and significant reduction of HR frequency. Cells expressing the mutant NBS1 were slightly sensitive to X-rays compared to the cells ectopically expressing wild-type NBS1. This difference in radiosensitivity between wild-type and mutant NBS1-expressing cells was enhanced when the cells were irradiated with a split dose. These observations suggest that partial inhibition of NBS1 suppress HR and inhibits recovery from sublethal damage.
