The Deubiquitinating Enzyme USP37 Stabilizes CHK1 to Promote the Cellular Response to Replication Stress

The deubiquitinating enzyme USP37 is known to contribute to timely S-phase onset. However, it is not clear if USP37 is essential beyond S-phase entry despite expression and activity of USP37 peaking within S-phase. Here, we determine that USP37-depleted cells exhibited altered S-phase kinetics and harbored increased levels of the replication stress and DNA damage markers γH2AX and 53BP1 in response to perturbed replication. Depletion of USP37 also reduced cellular proliferation and led to increased sensitivity to agents that induce replication stress. Underlying the increased sensitivity, we found that the checkpoint kinase CHK1 is destabilized in the absence of USP37, attenuating its function. We further demonstrated that USP37 deubquitinates and stabilizes CHK1. Our data contribute to an evolving understanding of UPS37 as a multifaceted regulator of genome regulation.

• Publication year

  2019

• Venue

  bioRxiv

• Publication date

  2019-05-29

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1101/652891
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

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