Fig. 1.

Signaling pathways of ATM and ATR

The DNA damage response is activated by ATM, ATR, and DNA-PKcs. All three play central roles in DDR. The ATM-CHK2 and ATR-CHK1 signaling pathways activate the HRR. The ATM and ATR pathways can be activated respectively by DSBs and SSBs. ATM activation can be regulated by Tip60, MRN complex, ATR, and PP2A as well as Wip1. The activated ATM can further trigger the activation of CHK2, SMC-1, FANCD2, BRCA1, as well as H2AX. In addition, the activated CHK2 can phosphorylate Cdc25A and p53. The ATR pathway can be activated by ATRIP, TopBP1, claspin, and 9-1-1 complex. The activation of ATR leads to phosphorylation of various downstream targets such as CHK1, SMC-1, ATM, and p21. Furthermore, CHK1 can facilitate phosphorylation of Wee1, RAD51, Cdc25A, p65, and Rb