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. Author manuscript; available in PMC: 2021 Jun 18.
Published in final edited form as: Mol Cell. 2020 May 26;78(6):1070–1085. doi: 10.1016/j.molcel.2020.04.035

Figure 2: The ATR/CHK1/WEE1 pathway compensates for the replicative stress induced by gemcitabine.

Figure 2:

Gemcitabine causes replicative stress by irreversibly inhibiting ribonucleotide reductase and thereby decreasing dNTP concentration. Decreased dNTP concentration causes stalled replication forks. In response to this replicative stress, the ATR/CHK1/WEE1 pathway is activated and this leads to stabilization of the replicative forks. However, inhibitors of the ATR/CHK1/WEE1 pathway block this compensatory pathway. This leads to persistence of unstable replication forks and ultimately causes genomic catastrophe leading to cancer cell death.