The shortening of telomeres with each cell division is counteracted by telomerase, which extends these repetitive sequences that cap the ends of linear chromosomes. The squeaky telomere gets the grease, however, as shorter ends seem to recruit or activate more telomerase.
Bianchi and Shore set out to examine the basis of this inequality by comparing individual short and long telomeres. “We expected to see a quantitative difference in the binding of telomerase or Cdc13, which activates it,” says Bianchi. “But instead we noticed a shift in the replication timing.” Shorter telomeres were replicated earlier in S phase.
The early start comes from an earlier firing of replication origins. Origins near long telomeres consistently fired late, but those near short telomeres were more likely to fire early. The mechanistic basis of this difference is still unclear.
The head start on replication corresponded with the creation of longer telomeres. Longer extension may be due to the noted advanced arrival of Cdc13 to early firing origins along with DNA polymerase. Telomerase inhibitors, on the other hand, were not affected by replication timing.