For long-term survival a cell must take care of its telomeres. It needs to protect them from the DNA-repair apparatus — which might otherwise view them as double-stranded breaks — while making sure that they are completely replicated during cell division. Reports in Cell and Genes and Development by Vicki Lundblad and colleagues now show that these two functions are reconciled in yeast through a telomere-binding protein called Cdc13 .

Lundblad's group previously showed that Cdc13 can positively regulate telomere replication by recruiting the enzyme responsible — telomerase — to chromosome ends. But Cdc13 also negatively modulates telomere replication — an effect that occurs after the recruitment of telomerase, and depends on a protein known as Stn1.

One explanation for this negative regulation is the recruitment, by Cdc13, of an end-protecting activity. The obvious candidate is Stn1, so the authors fused the DNA-binding domain of Cdc13 to Stn1. Expression of this construct rescued the lethality of a cdc13 null strain, suggesting that Stn1 is the arbiter of end protection and that it is delivered to telomeres by Cdc13.

The association of Cdc13 with both telomerase and Stn1 is blocked by a single mutation (cdc13-2), leading Lundblad and colleagues to describe how Cdc13 might regulate telomere replication. According to their model, telomerase is delivered to the DNA end in the first (positive) step. Then, in the second (negative) step, Stn1 binds an overlapping site on Cdc13, allowing it, in turn, to be recruited to the telomere.