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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
Summary
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.
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