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DNA-damage tolerance through PCNA ubiquitination and sumoylation

Li Fan1,2, Tonghui Bi2, Linxiao Wang1,2

  • 1Department of Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada S7N 5E5.

The Biochemical Journal
|July 30, 2020
PubMed

Insights

Eukaryotic cells use DNA-damage tolerance (DDT) to bypass DNA lesions during replication. This process involves modifying proliferating cell nuclear antigen (PCNA) through ubiquitination and sumoylation, with conserved enzymes across species.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cell Biology

Background:

  • DNA-damage tolerance (DDT) is crucial for eukaryotic cells to navigate replication-blocking lesions.
  • Prokaryotic cell nuclear antigen (PCNA) is a central DNA clamp involved in replication and repair.
  • PCNA undergoes sequential post-translational modifications, including ubiquitination and sumoylation.

Purpose of the Study:

  • To elucidate the mechanisms of DNA-damage tolerance (DDT) in Saccharomyces cerevisiae.
  • To detail the roles of PCNA ubiquitination and sumoylation in DDT pathways.
  • To highlight the evolutionary conservation of DDT enzymes.

Main Methods:

  • Focus on genetic studies in Saccharomyces cerevisiae.
  • Analysis of PCNA ubiquitination and sumoylation.
  • Investigating the functions of RAD6 epistatic group genes.

Main Results:

  • DDT involves two parallel pathways: error-prone (via monoubiquitination) and error-free (via K63-linked polyubiquitination) PCNA modifications.
  • PCNA sumoylation inhibits recombination at replication forks.
  • The enzymes mediating these PCNA modifications are conserved from yeast to humans.

Conclusions:

  • PCNA post-translational modifications are key regulatory events in DNA-damage tolerance.
  • Distinct ubiquitination and sumoylation pathways ensure genome stability.
  • Conserved enzymatic machinery underscores the fundamental importance of DDT in eukaryotes.
Keywords:
schizosaccharomyces pombemycesDNA-damage tolerancePCNAsumoylationubiquitins

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