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Updated: Jul 8, 2025

Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis
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Combining Mitotic Cell Synchronization and High Resolution Confocal Microscopy to Study the Role of Multifunctional Cell Cycle Proteins During Mitosis

Published on: December 5, 2017

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FBH1 deficiency sensitizes cells to WEE1 inhibition by promoting mitotic catastrophe

Lucy Jennings1, Heather Andrews Walters1, Tyler J McCraw1

  • 1Department of Genetics and Biochemistry, Clemson University, United States.

DNA Repair
|December 16, 2023
PubMed

Insights

Loss of the helicase FBH1 sensitizes cancer cells to WEE1 inhibition by increasing mitotic catastrophe. FBH1 is required for the replication stress response following WEE1 inhibition.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • WEE1 kinase regulates cell cycle progression by phosphorylating CDK1/CDK2.
  • WEE1 inhibition is a promising cancer therapy, inducing replication stress and G2/M checkpoint abrogation.
  • Understanding genetic factors influencing WEE1 inhibitor response is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of the helicase FBH1 in cellular response to WEE1 inhibition.
  • To determine if FBH1 deficiency impacts WEE1 inhibitor-induced replication and mitotic stress.

Main Methods:

  • Utilized WEE1 inhibitors in cancer cell models.
  • Assessed DNA damage signaling (ssDNA, double-strand breaks) in response to WEE1 inhibition.
  • Evaluated FBH1-deficient cells for sensitivity to WEE1 inhibition and cell death induction.

Main Results:

  • FBH1-deficient cells showed reduced replication stress response signaling upon WEE1 inhibition.
  • Despite impaired replication stress signaling, FBH1-deficiency sensitized cells to WEE1 inhibition.
  • Increased mitotic catastrophe was observed in FBH1-deficient cells treated with WEE1 inhibitors.

Conclusions:

  • FBH1 is essential for the induction of the replication stress response following WEE1 inhibition.
  • Loss of FBH1 enhances sensitivity to WEE1 inhibition, primarily through increased mitotic catastrophe.
  • Replication-associated damage in FBH1-deficient cells may rely on the WEE1-dependent G2 checkpoint for repair.
Keywords:
DNA repairFBH1MitosisReplicationReplication catastropheWEE1

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