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Updated: Jun 6, 2025

A Simple, Rapid, and Quantitative Assay to Measure Repair of DNA-protein Crosslinks on Plasmids Transfected into Mammalian Cells
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A Simple, Rapid, and Quantitative Assay to Measure Repair of DNA-protein Crosslinks on Plasmids Transfected into Mammalian Cells

Published on: March 5, 2018

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Transcription-coupled repair of DNA-protein crosslinks

Christopher J Carnie1, Stephen P Jackson1, Julian Stingele2

  • 1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK.

Trends in Cell Biology
|December 1, 2024
PubMed

Insights

DNA-protein crosslinks (DPCs) are toxic lesions repaired by a transcription-coupled pathway involving Cockayne syndrome proteins. This pathway

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA-protein crosslinks (DPCs) are harmful DNA lesions implicated in human diseases.
  • DPCs arise from endogenous/environmental factors and enzyme actions, obstructing DNA replication.
  • The impact of DPCs on RNA polymerases was previously unclear.

Purpose of the Study:

  • To investigate the consequences of DPC-induced RNA polymerase blockade.
  • To discover and characterize a transcription-coupled DPC repair pathway.

Main Methods:

  • Utilized novel methodologies for studying DPC repair.
  • Investigated the role of RNA polymerase II (RNAPII) stalling in DPC repair initiation.
  • Examined the involvement of Cockayne syndrome (CS) proteins CSB and CSA.

Main Results:

  • Discovered a transcription-coupled (TC) DPC repair pathway.
  • RNAPII stalling triggers TC-DPC repair.
  • TC-DPC repair involves sequential engagement of CSB and CSA, leading to proteasomal DPC degradation.

Conclusions:

  • TC-DPC repair is a critical pathway for resolving DPC-induced transcription stress.
  • Deficiencies in CSA or CSB impair TC-DPC repair, potentially explaining Cockayne syndrome clinical features.
Keywords:
Cockayne syndromeDNA repairformaldehydenucleotide excision repair

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