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 (ME Fs) derived from either wild-type or Ku80-null (Ku80(-/-)) mice with variou s stress agents revealed that hydrogen peroxide (H2O2) was markedly more cy totoxic for Ku80(-/-) MEFs and led to their long-term accumulation in the G 2 phase. This differential response was not due to differences in DNA repai r, since H2O2-triggered DNA damage was repaired with comparable efficiency in both Wt and Ku80-/- MEFs, but was associated with differences in the exp ression of important cell cycle regulatory genes. Our results support the n otion that Ku80-mediated cytoprotection and G2-progression are not only dep endent on the cell's DNA repair but also may reflect Ku80's influence on ad ditional cellular processes such as gene expression. (C) 2000 Elsevier Scie nce Inc.