Figure 6.

Putative model for the role of WIP1 in HR and in PARP inhibitor sensitivity. (A) Under normal conditions, endogenous DNA lesions are efficiently repaired by HR and BER. WIP1 promotes efficiency of HR and limits the extent of p53 pathway activation allowing cells to proliferate. (B) After inhibition of PARP1, BER pathway is impaired (dashed lines) but DNA lesions are efficiently repaired by HR. (C) Combined inhibition of PARP1 and WIP1 impairs both BER and HR (dashed lines) and enhances p53 response leading to accumulation of DNA lesions in G2 cells. Increased DNA damage load triggers the DNA damage response and allows full activation of p53 pathway leading to cell death.