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The Aspartic Protease Ddi1 Contributes to DNA-Protein Crosslink Repair in Yeast.
Journal article

The Aspartic Protease Ddi1 Contributes to DNA-Protein Crosslink Repair in Yeast.

  • Serbyn N Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: nataliia.serbyn@unige.ch.
  • Noireterre A Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland.
  • Bagdiul I Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland.
  • Plank M Department of Molecular Biology and the Swiss National Centre for Competence in Research Program Chemical Biology, University of Geneva, 1211 Geneva 4, Switzerland.
  • Michel AH Institute of Biochemistry, ETH Zürich, 8093 Zurich, Switzerland; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
  • Loewith R Department of Molecular Biology and the Swiss National Centre for Competence in Research Program Chemical Biology, University of Geneva, 1211 Geneva 4, Switzerland.
  • Kornmann B Institute of Biochemistry, ETH Zürich, 8093 Zurich, Switzerland; Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK.
  • Stutz F Department of Cell Biology, University of Geneva, 1211 Geneva 4, Switzerland. Electronic address: francoise.stutz@unige.ch.
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  • 2020-01-07
Published in:
  • Molecular cell. - 2020
26S proteasome
DNA-protein crosslink
Ddi1
Flp recombinase
RNA polymerase II
Rpb1
Top1
Wss1
protease
yeast
Animals
DNA Damage
DNA Nucleotidyltransferases
DNA Repair
DNA Topoisomerases, Type I
DNA, Fungal
Gene Expression Regulation, Fungal
Phosphoric Diester Hydrolases
Proteolysis
RNA Polymerase II
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Sf9 Cells
Spodoptera
Transcription, Genetic
English Naturally occurring or drug-induced DNA-protein crosslinks (DPCs) interfere with key DNA transactions if not repaired in a timely manner. The unique family of DPC-specific proteases Wss1/SPRTN targets DPC protein moieties for degradation, including stabilized topoisomerase-1 cleavage complexes (Top1ccs). Here, we describe that the efficient DPC disassembly requires Ddi1, another conserved predicted protease in Saccharomyces cerevisiae. We found Ddi1 in a genetic screen of the tdp1 wss1 mutant defective in Top1cc processing. Ddi1 is recruited to a persistent Top1cc-like DPC lesion in an S phase-dependent manner to assist in the eviction of crosslinked protein from DNA. Loss of Ddi1 or its putative protease activity hypersensitizes cells to DPC trapping agents independently from Wss1 and 26S proteasome, implying its broader role in DPC repair. Among the potential Ddi1 targets, we found the core component of Pol II and show that its genotoxin-induced degradation is impaired in ddi1. We propose that the Ddi1 protease contributes to DPC proteolysis.
Language
  • English
Open access status
green
Identifiers
Persistent URL
https://sonar.ch/global/documents/185485
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