Figure 3

SSBs function in cell cycle checkpoint activation. (A) Schematic of the potential role of RPA in ATR signalling: RPA coated ssDNA stimulates ATR signalling both through direct interaction with its binding partner ATRIP, as well as through the 9-1-1 complex. Activated ATR phosphorylates various cell cycle checkpoint proteins, including p53 and CHK1, allowing for cell cycle arrest. RPA also interacts with RFWD3, an E3 ubiquitin ligase involved in p53 stabilisation. (B) Schematic of the potential role of hSSB1 and Strap in ATM signalling: hSSB1 activation allows for the recruitment of the MRN complex, which activates the ATM kinase. ATM phosphorylation of hSSB1 then facilitates a positive feedback loop, which further activates ATM, as well as many downstream ATM targets. hSSB1 also interacts with and stabilises p53 and p21 (an effector of p53 signalling), as well as the p53-interacting acetyltransferase p300. Strap, a phosphorylation substrate of ATM, interacts with and stabilises p53, and additionally directs it to transcriptional targets.