Turning telomeres off and on.

We envision multiple steps in telomere maintenance, based largely on genetic data from budding yeast. First, the telomere must unfold or open itself such that the free end is accessible to the appropriate enzymatic machinery. Second, telomerase must be recruited, together with the DNA replication machinery that synthesizes the C-rich strand. The processivity of telomerase is regulated both by a length-sensing feedback mechanism and by second-strand synthesis. Finally, the telosome refolds into a protective end structure. If telomerase is nonfunctional, recombination may occur once telomeres are open. Multiple pathways regulate these different steps, producing a highly dynamic chromosomal cap.