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The DNA damage tolerance factor Rad5 and telomere replication
1Université Paris-Saclay, Université Paris-Cité, CEA, Institut de biologie François Jacob, UMR Stabilité Génétique Cellules Souches et Radiations, Fontenay-aux-Roses, Inserm, France. stefano.mattarocci@inserm.fr.
Abstract:
The DNA Damage Tolerance pathway (DDT) is one of the major mechanisms for resolving replication fork blocks. A key factor in DDT is the fork-associated clamp PCNA, which can undergo to mono- or polyubiquitination, leading to error-prone or error-free modes of DNA damage bypass, respectively. In the yeast Saccharomyces cerevisiae, Rad5HLTF/SNF2 factor plays important roles in both pathways: (i) promoting the error-free mode through PCNA polyubiquitination and transient template switching and (ii) interacting with specialized DNA polymerases involved in the error-prone pathway. Rad5 also associates with telomeres, the repetitive DNA regions present at the ends of chromosomes. Telomeric DNA, tightly bound by tandem proteins arrays, poses unique challenges to replication fork progression. Here, I review the current understanding of the link between Rad5 and telomeres and provide evidence that Rad5 binds to yeast telomeres, with notable enrichment during telomere replication. This finding highlights a connection between telomeres and an important DDT factor in unperturbed wild-type cells, raising intriguing possibilities regarding the functional interplay between telomere replication and DNA damage tolerance mechanisms.
Insights
The DNA Damage Tolerance (DDT) pathway uses Rad5 to help replicate DNA past blocks. Rad5 binds to telomeres, suggesting a role in telomere replication and DNA repair.
Area of Science:
- Molecular Biology
- Genetics
- Cell Biology
Background:
- DNA replication requires mechanisms to overcome blocks, such as the DNA Damage Tolerance (DDT) pathway.
- PCNA ubiquitination is central to DDT, mediating error-free or error-prone DNA damage bypass.
- Rad5 is a key factor in yeast Saccharomyces cerevisiae, influencing both DDT pathways and interacting with telomeres.
Purpose of the Study:
- To review the current understanding of the link between Rad5 and telomeres.
- To present evidence for Rad5 binding to yeast telomeres.
- To explore the functional interplay between telomere replication and DNA damage tolerance.
Main Methods:
- Literature review of Rad5 function in DNA Damage Tolerance.
- Experimental evidence demonstrating Rad5 binding to telomeres in Saccharomyces cerevisiae.
- Analysis of Rad5 enrichment during telomere replication.
Main Results:
- Rad5 plays a dual role in DDT, promoting error-free bypass via PCNA polyubiquitination and interacting with polymerases for error-prone bypass.
- Rad5 demonstrates binding to yeast telomeres.
- Rad5 shows enrichment at telomeres specifically during their replication.
Conclusions:
- Rad5 is functionally linked to telomeres in yeast.
- The findings suggest a novel connection between telomere replication and DNA damage tolerance mechanisms.
- Further research is warranted to elucidate the precise role of Rad5 at telomeres during replication.
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