The DNA damage tolerance factor Rad5 and telomere replication.

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, Rad5 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.