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. Author manuscript; available in PMC: 2017 Nov 23.
Published in final edited form as: Trends Cancer. 2016 Nov 23;2(11):646–656. doi: 10.1016/j.trecan.2016.10.014

Figure 2. Effect of DNA Damage Repair Inhibitors on Cell Cycle Progression.

Figure 2

TP53 is a sensor that guards the integrity of the genome by altering progression through the cell cycle at the G1/S, S, and G2/M checkpoints. Progression through the cell cycle is tightly regulated by cyclins and cyclin-dependent kinases. Blockade of cell cycle checkpoints propagates DNA damage by permitting the replication of unrepaired DNA and increasing mutational burden. All these events lead to genomic instability and enhanced susceptibility to DNA repair inhibitors, such as those listed on the figure.

Abbreviations: i, inhibitor; DNARi, DNA repair inhibition; CHEK1, checkpoint kinase 1 inhibitor; CHEK1/2i, checkpoint kinases 1/2; WEE1, WEE1 G2 checkpoint kinase; MYT1, myelin transcription factor 1; CDK1/2, cyclin dependent kinases 1/2; CDK4/6/9, cyclin dependent kinases 4/6/9; ATR, ataxia telangiectasia and Rad3-related kinase; DNA-PKCS, DNA-dependent protein kinase catalytic subunit; MDM2, MDM2 proto-oncogene; TP53, tumor protein p53.