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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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SUMO orchestrates multiple alternative DNA-protein crosslink repair pathways

Nataliia Serbyn1, Ivona Bagdiul1, Audrey Noireterre1

  • 1Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland.

Cell Reports
|November 24, 2021
PubMed

Insights

SUMO biogenesis factors regulate DNA repair pathways. SUMOylation inhibits alternative DNA-protein crosslink (DPC) repair mechanisms when Tdp1 and Wss1 are absent, ensuring genome integrity.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Covalent DNA-protein crosslinks (DPCs) arise from various sources and threaten genome stability.
  • Multiple repair pathways exist to eliminate persistent DPCs, but the selection mechanism remains unclear.
  • Topoisomerase 1-DNA crosslinks (Top1ccs) are a specific type of DPC repaired by Tdp1 and Wss1 in yeast.

Purpose of the Study:

  • To investigate the role of SUMO (Small Ubiquitin-like Modifier) biogenesis factors in DPC repair.
  • To elucidate how cells choose between different DPC repair mechanisms.
  • To understand the interplay between SUMOylation and DPC repair pathways.

Main Methods:

  • Genetic analysis in Saccharomyces cerevisiae.
  • Investigating the function of SUMO biogenesis factors (Ulp1, Siz2, Slx5, Slx8).
  • Assessing Top1cc processing in various mutant backgrounds (tdp1Δ, wss1Δ, tdp1Δ wss1Δ).

Main Results:

  • SUMO biogenesis factors control the repair of Top1ccs and analogous DPCs.
  • SUMO promotes Top1cc processing when Tdp1 is absent.
  • SUMO inhibits alternative DPC repair (e.g., Ddi1) in a Tdp1- and Wss1-deficient background, mediated by Siz2-dependent sumoylation near the DPC.

Conclusions:

  • SUMOylation acts as a regulatory mechanism in DPC repair.
  • The SUMO pathway influences the choice between parallel DPC repair routes.
  • SUMOylation fine-tunes repair pathway selection to maintain genome integrity.
Keywords:
DNA-protein crosslinkDPC repairFlp-nickSTUbLSUMOSiz2Tdp1Top1Top1ccUlp1Wss1

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