Fig. 7. Proposed model for activation of the ATR-p53-p21 pathway induced by increasing the amount of PCs that contain polyunsaturated fatty acids in membrane phospholipids. Under physiological conditions, the levels of polyunsaturated fatty acids in cell-membranous PCs in are precisely regulated by a iPLA₂-mediated deacylation and reacylation cycle. Inhibition of iPLA₂ results in an increase of phospholipids that contain polyunsaturated fatty acids, which may alter the fluidity of cell membranes especially nuclear envelopes. This leads to activation of the ATR-p53-p21 signalling pathway to prevent cells from entering the S phase of the cell cycle. In the absence of p21, the alteration in membrane phospholipids leads to apoptosis (Zhang et al., 2006). PUFA, polyunsaturated fatty acids; SFA, saturated fatty acids; LysoPC, lysophosphatidylcholine.