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Updated: Aug 13, 2025

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
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Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

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SPRTN patient variants cause global-genome DNA-protein crosslink repair defects

Pedro Weickert1,2, Hao-Yi Li1,2, Maximilian J Götz1,2

  • 1Department of Biochemistry, Ludwig-Maximilians-University, 81377, Munich, Germany.

Nature Communications
|January 21, 2023
PubMed

Insights

Researchers developed a new method to track DNA-protein crosslinks (DPCs). They discovered the SPRTN protease repairs DPCs independently of DNA replication, a finding crucial for understanding premature aging and cancer.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA-protein crosslinks (DPCs) are common DNA lesions formed by metabolites and chemotherapy.
  • Accumulation of DPCs can lead to cellular dysfunction and disease.

Purpose of the Study:

  • To develop a novel technique for identifying and tracking DPCs in mammalian cells.
  • To investigate the role of the SPRTN protease in DPC repair, particularly in the context of Ruijs-Aalfs syndrome.

Main Methods:

  • Development of the Purification of x-linked Proteins (PxP) technique.
  • Utilizing genetically engineered mammalian cells expressing SPRTN variants.
  • Investigating DPC repair mechanisms, including replication-independent pathways.

Main Results:

  • The PxP technique enables the identification and tracking of diverse DPCs.
  • SPRTN plays an unexpected role in global-genome DPC repair, independent of DNA replication.
  • Replication-independent DPC repair by SPRTN requires SUMO-targeted ubiquitylation and complements proteasomal degradation.

Conclusions:

  • SPRTN is essential for global-genome DPC repair through a novel replication-independent mechanism.
  • Defective SPRTN ubiquitin binding impairs DPC repair, leading to synthetic lethality with reduced proteasomal DPC repair.

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