TRIP12's role in the governance of DNA polymerase β involvement in DNA damage response and repair

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Updated: Sep 17, 2025

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

Published on: June 8, 2018

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Burcu Inanc1, Qingming Fang2,3, Wynand P Roos4

  • 1Division of Cell Biology, The Netherlands Cancer Institute, Amsterdam 1066CX, The Netherlands.

Nucleic Acids Research
|July 4, 2025
PubMed

Insights

TRIP12, a DNA repair regulator, controls DNA polymerase beta (Polβ) ubiquitylation and levels, ensuring base excision repair (BER) precedes double-strand break (DSB) repair for genome stability.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Maintaining genome integrity involves complex DNA repair pathways.
  • Cross-talk between double-strand break (DSB) repair and base excision repair (BER) is crucial but poorly understood.
  • Specific regulators coordinating these pathways remain unidentified.

Purpose of the Study:

  • To identify regulators controlling DNA repair pathway crosstalk.
  • To investigate the role of E3 ligase TRIP12 in coordinating BER and DSB repair.
  • To elucidate the mechanism of Polβ regulation in DNA damage response.

Main Methods:

  • Ubiquitylation assays to study Polβ modification.
  • Western blotting and chromatin immunoprecipitation to assess protein levels and localization.
  • Radiation sensitivity assays to evaluate DNA repair efficiency.
  • Immunofluorescence microscopy to visualize DNA repair foci.

Main Results:

  • TRIP12, an E3 ligase, ubiquitylates DNA polymerase beta (Polβ) in a BER complex-dependent manner.
  • TRIP12, but not UBR5, regulates cellular Polβ levels and chromatin loading.
  • TRIP12-mediated ubiquitylation of Polβ is essential for Polβ foci formation and its involvement in radiation-induced DNA damage.
  • Dysregulation of TRIP12 impacts DSB formation and radiation sensitivity, favoring BER over DSB repair.

Conclusions:

  • TRIP12 governs Polβ-directed BER, ensuring efficient lesion removal at complex DSB sites.
  • TRIP12 acts as a critical coordinator at the nexus of DNA repair pathways.
  • This discovery highlights TRIP12's role in maintaining genome stability by prioritizing BER.

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