Figure 1.

T-loop regulation may require precise temporal regulation. The displacement loop likely inhibits the smooth passage of the DNA replication machinery upon telomere replication. It has been suggested that the RTEL1 helicase is able to resolve the t-loop structure and allow replication fork passage while at the same time providing telomerase access to the 3′ ss overhang. In the absence of RTEL1 the replication machinery may encounter the t-loop junction, resulting in fork stalling and the subsequent SLX4-mediated excision of a t-circle, which leads to rapid telomere loss. In this situation (RTEL absent) the loss is compounded by the inability of telomerase to act. Upon the completion of telomere replication the loop must be re-established. Therefore, a complete switch from t-loop resolving to t-loop promoting activities must take place. As the HDR factors RAD51 and RAD52, which are necessary for t-loop formation, get loaded onto telomeres, we suggest that RTEL1 must get actively removed. Together these activities would sequentially promote telomere replication, telomerase elongation, and the re-establishment of a protective loop structure.