Figure 1.

Upon replication stress caused by various types of DDA, SLFN11-proficient cells undergo an enforced G1/S arrest ultimately resulting in cell death (B). On the contrary, SLFN11-deficient cells reliant on the ATR/CHK1 pathway re-enter the cell cycle, slowly progress through the S-phase, and following DNA repair can survive (A). SLFN11 expression can be reactivated by the inhibitors of epigenetic modulators, such as DNA methyltransferase (DNMT), histone deacetylase (HDAC), or EZH2 inhibitors. Resistance of SLFN11-deficient cells can be overcome by combination with ATR/CHK1/WEE1 inhibitors.