抄録
Werner syndrome (WS) is an autosomal recessive disorder with many features of premature ageing. The life span of fibroblasts derived from WS patients is much shorter than that of normal fibroblasts. WS cells also show genomic instability and sensitivity to certain genotoxic agents. The responsible gene for WS, WRN belongs to RecQ helicase family and exhibits 3' to 5' helicase and 3' to 5' exonuclease activities, and interacts with Ku, DNA-PKcs, RPA and NBS1. DNA repair-related genes such as NBS1, BRCA1 and MDC1 are recruited to DNA damage sites for DNA repair. AS WRN might function for DNA repair, WRN could be recruited to DNA damage sites. Therefore, we investigated the foci formation of WRN in response to DNA damage.
The formation of WRN foci was detected in response to DSBs induced by X-ray, bleomycin or etposide in HeLa cells. AT and NBS cells showed these foci formation. Camptothecin, or hydroxyurea, which stall the DNA replication and induce DSBs, also induced WRN foci formation. Moreover, S phase cells showed WRN foci in response to DNA damage, but G1 phase cells didn't. Therefore, WRN is recruited to DNA damage site only in S phase and function for DNA repair.
