Abstract
The ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) protein kinases, which are members of phosphatidyl inositol 3-kinase-like kinase family, play central roles in DNA damage checkpoints. ATM is primarily activated by DNA double-strand breaks (DSBs) caused by ionizing radiation or radiomimetic drugs. Activation of ATM is stimulated by the MRE11-RAD50-NBS1 (MRN) complex. On the other hand, in response to UV damage or other replication blocking stress, ATR is activated by TopBP1 and phosphorylates several substrates, including Chk1. In the NBS1 deficient cells, Chk1 phosphorylation after UV irradiation is impaired, suggesting that activation of the ATR-mediated pathway also requires NBS1. However, its precise mechanism is unknown. In this study, we investigated whether NBS1 is required for ATR localization to DNA damage sites after UV irradiation. Roles of NBS1 in the ATR pathway will be discussed.
