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. 2016 Dec 22;8(7):10966–10979. doi: 10.18632/oncotarget.14089

Figure 5. Model.

Figure 5

(A) Wee1-inhibition alone causes very high CDK activity in S-phase, but Chk1 mediated suppression of CDC45 loading limits replication initiation. This results in low levels of S-phase DNA damage. (B) Chk1-inhibition alone causes a moderate increase in CDC45 loading, which is limited due to Wee1 mediated suppression of CDK activity. This results in moderate levels of S-phase DNA damage. (C) Simultaneous Wee1- and Chk1- inhibition removes the restraints on both CDK activity and CDC45 loading. Consequently, there is a strong increase in CDC45 loading and subsequent massive DNA damage in S-phase.