Proteomics

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USP37 protects mammalian cells during DNA replication stress by counteracting CUL2-LRR1 and TRAIP

ABSTRACT: We have found that the USP37 deubiquitylase binds to the DNA helicase known as CMG (Cdc45-Mcm-GINS) in mammalian cells. CMG unwinds the parental DNA duplex during the process of chromosome duplication, and USP37 is important to help cells survive problems in DNA replication.In this project, we investigated the partners of the mammalian CMG helicase. We compared control mouse embryonic stem cells (mES cells) to mES cells in which the SLD5 component of the CMG helicase was fused to the ‘Tandem Affinity Purification’ tag (TAP-tag). Cells were either untreated or exposed to 5 µM CB-5083 for three hours, to inhibit activity of the p97 ATPase.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: KARIM LABIB  

LAB HEAD: Professor Karim

PROVIDER: PXD056491 | Pride | 2026-06-09

REPOSITORIES: Pride

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USP37 protects mammalian cells during DNA replication stress by counteracting CUL2<sup>LRR1</sup> and TRAIP.

Villa Fabrizio F   Ainsworth Johanna J   Labib Karim P M KPM  

Cell reports 20250522 6

The USP37 deubiquitylase is essential for mammalian cells to survive DNA replication stress, but the underlying mechanisms are unknown. Here, we demonstrate that USP37 binds the CDC45-MCM-GINS (CMG) helicase, which forms the stable core of the replisome until DNA replication termination when CMG is ubiquitylated and disassembled. USP37 contacts CDC45, and structure-guided mutations that displace USP37 from CMG cause sensitivity to DNA synthesis defects or topological stress. Binding to CDC45 at  ...[more]

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