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USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication.

Santiago Hernández-Pérez1, Elisa Cabrera1, Hugo Amoedo1

  • 1Unidad de Investigación, Hospital Universitario de Canarias, Instituto de Tecnologías Biomédicas, Ofra s/n, La Laguna, Tenerife, Spain.

Molecular Oncology
|June 15, 2016
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Summary
This summary is machine-generated.

The deubiquitinase USP37 stabilizes Cdt1, a key protein in DNA replication initiation. USP37 regulates Cdt1 levels, impacting DNA replication fork speed and genomic integrity.

Keywords:
DNA damageDNA damage responseInitiation of DNA replicationProteasomeProtein degradationUbiquitin hydrolase

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genomics

Background:

  • DNA replication initiation requires precise control to ensure genomic integrity.
  • Cdt1 protein levels are tightly regulated throughout the cell cycle via ubiquitination and degradation.
  • Origin recognition complex (ORC), Cdt1, and Cdc6 proteins license DNA replication origins by recruiting MCM2-7 helicase.

Purpose of the Study:

  • To identify ubiquitin hydrolases that regulate Cdt1.
  • To investigate the role of USP37 in Cdt1 regulation and DNA replication.

Main Methods:

  • Overexpression screen to identify Cdt1 deubiquitinating enzymes.
  • USP37 knockdown and overexpression studies.
  • In vivo deubiquitination assays.
  • Chromatin loading assays for MCM complexes.
  • Measurement of DNA replication fork speed.

Main Results:

  • USP37 was identified as the first ubiquitin hydrolase controlling Cdt1.
  • USP37 overexpression stabilizes Cdt1, while USP37 knockdown destabilizes it, particularly in G1/S phases.
  • USP37 interacts with Cdt1, deubiquitinates it in vivo, and regulates MCM complex loading onto chromatin.
  • Downregulation of USP37 leads to reduced DNA replication fork speed.

Conclusions:

  • The deubiquitinase USP37 plays a significant role in regulating DNA replication.
  • USP37 stabilizes Cdt1, a crucial protein for DNA replication initiation.
  • USP37's function in DNA replication may involve Cdt1 or additional factors.