Abstract
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 such as 4NQO. The responsible gene for WS, WRN belongs to RecQ helicase family and exhibits 3' to 5' helicase and 3' to 5' exonuclease activities. WRN protein forms foci at DNA damage site and interacts with Ku, DNA-PKcs, RPA and NBS1, suggesting that WRN functions for DNA repair. Recently, NBS1 was identified as a new interacting protein with WRN and functions in DNA repair and cell cycle checkpoints. Therefore, we investigated the functional interaction between WRN and NBS1 in DNA damage response.
As reported, WRN formed the complex with NBS1 with and without DNA damage and this complex also cotained BRCA1. In NBS cells WRN cannot form nuclear foci following exposure to IR and camptothecin treatment. WRN is phosphorylated in response to DNA damage, but this phosphorylations is defect in NBS cells. Moreover, the NBS1, mutated in FHA domain, cannot bind with WRN and not induce WRN phosphorylation. Taken together, NBS1 might mediate WRN function in DNA damage response such as recruitment and phopshorylation through interaction.
