Figure 2. DNA damage detected at the G₂ checkpoint. Depending on the type of genotoxic stress, either ataxia-telangectasia mutated (ATM) protein kinase or ataxia-telangiectasia-related (ATR) protein kinase are preferentially activated. ATR is the main kinase responsible for the phosphorylation and activation of checkpoint kinase 1 (Chk1). Chk1, in turn, concomitantly phosphorylates wee1 and Cdc25C, thereby activating wee1 kinase activity and inactivating Cdc25C phosphatase activity. Wee1 phosphorylates and inactivates Cdk1/Cdc2-bound cyclin B on its tyrosine15 residue, resulting in cell cycle arrest at G₂, allowing time for DNA repair. Abbreviations: ATM, ataxia-telangectasia mutated protein kinase; ATR, ataxia-telangiectasia-related protein kinase; Chk, checkpoint kinase; Cdk, cyclin-dependent kinase; Cdc, cell division cycle phosphatase.