Stn1-Ten1 and Taz1 independently promote replication of subtelomeric fragile sequences in fission yeast

Efficient replication of terminal DNA is crucial to maintain telomere stability. In fission yeast, Taz1 and the Stn1-Ten1 (ST) complex play prominent roles in DNA-ends replication. However, their function remains elusive. Here, we have analyzed genome-wide replication and show that ST does not affect genome-wide replication but is crucial for the efficient replication of a subtelomeric region called STE3-2. We further show that, when ST function is compromised, a homologous recombination (HR)-based fork restart mecha-nism becomes necessary for STE3-2 stability. While both Taz1 and Stn1 bind to STE3-2, we find that the STE3-2 replication function of ST is independent of Taz1 but relies on its association with the shelterin pro-teins Pot1-Tpz1-Poz1. Finally, we demonstrate that the firing of an origin normally inhibited by Rif1 can circumvent the replication defect of subtelomeres when ST function is compromised. Our results help illumi-nate why fission yeast telomeres are terminal fragile sites.

Automated summary

Efficient replication of terminal DNA is important for telomere stability. In fission yeast, the Stn1-Ten1 complex is crucial for replication of a subtelomeric region called STE3-2, and its function relies on its association with shelterin proteins. When Stn1-Ten1 function is compromised, a homologous recombination-based fork restart mechanism becomes necessary for STE3-2 stability. The firing of an origin normally inhibited by Rif1 can bypass the replication defect of subtelomeres.