Enhanced sensitivity and long-term G2 arrest in hydrogen peroxide-treated Ku80-null cells are unrelated to DNA repair defects

While the Ku complex, comprised of Ku70 and Ku80, is primarily involved in the repair of DNA double-strand breaks, it is also believed to participate in additional cellular processes. Here, treatment of embryo fibroblasts (MEFs) derived from either wild-type or Ku80-null (Ku80−/−) mice with various stress agents revealed that hydrogen peroxide (H2O2) was markedly more cytotoxic for Ku80−/− MEFs and led to their long-term accumulation in the G2 phase. This differential response was not due to differences in DNA repair, since H2O2-triggered DNA damage was repaired with comparable efficiency in both Wt and Ku80−/− MEFs, but was associated with differences in the expression of important cell cycle regulatory genes. Our results support the notion that Ku80-mediated cytoprotection and G2-progression are not only dependent on the cell’s DNA repair but also may reflect Ku80’s influence on additional cellular processes such as gene expression.