The deubiquitinating enzyme USP37 enhances CHK1 activity to promote the cellular response to replication stress.

ABSTRACT: The deubiquitinating enzyme USP37 is known to contribute to timely onset of S phase and progression of mitosis. However, it is not clear if USP37 is required beyond S-phase entry despite expression and activity of USP37 peaking within S phase. We have utilized flow cytometry and microscopy to analyze populations of replicating cells labeled with thymidine analogs and monitored mitotic entry in synchronized cells to determine that USP37-depleted cells exhibited altered S-phase kinetics. Further analysis revealed that cells depleted of USP37 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 str

SUBMITTER: Stromberg BR 

PROVIDER: S-EPMC8487067 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature