抄録
Mutation in NBS1 protein causes Nijimegen breakage syndrome (NBS) which cells exhibit hyper-radiosensitivity, abnormal S phase checkpoint and chromosomal instability. NBS1 forms a complex with Mre11/Rad50 to play critical roles in DNA double strands break (DSB) repair. We have reported that the Mre11 complex with functional NBS1 is essential for homologous recombination (HR) repair pathway. This suggest that NBS1 regulates the complex by controlling their subnuclear localization and enzymatic activities. To analyze functional domains of NBS1 in HR repair pathway, a SCneo reporter was introduced into NBS fibroblast cells. Full length or mutant NBS1 was expressed in the cells, and then DSB was induced by transient expression of I-SceI endonuclease. We found that Mre11-binding domain of NBS1 is the most critical domain for HR, and that ATM-phosphorylation sites of NBS1 is not essential for normal HR function whereas slight decrease in efficiency was observed.
