Rad5 and Telomere Replication

The DNA Damage Tolerance pathway (DDT) is one of the major mechanisms for resolving replication fork blocks. A central factor for DDT is the fork-associated clamp, PCNA, which can undergo to mono- or polyubiquitination, leading to error-free or error-prone modes of repair, respectively. The Rad5 protein in the yeast Saccharomyces cerevisiae plays important roles in both pathways: promoting the error-free mode by PCNA polyubiquitination and 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 present evidence that Rad5 is associated with yeast telomeres, with notable enrichment during telomere replication. This data highlights a connection between telomeres and a key DDT factor in unperturbed wild-type cells, raising intriguing possibilities about the functional interplay between telomere replication and DNA damage tolerance mechanisms.