How Shelterin Orchestrates the Replication and Protection of Telomeres

Efforts to determine how telomeres solve the end-protection problem led to the discovery of shelterin, a conserved six-subunit protein complex that specifically binds to the long arrays of telomeric TTAGGG repeats at vertebrate chromosome ends. The mechanisms by which shelterin prevents telomeres from being detected as sites of DNA damage and how shelterin prevents inappropriate DNA repair pathways are now largely known. More recently, shelterin has emerged as a central player in solving the second major problem at telomeres: how to complete the duplication of telomeric DNA. This end-replication problem results from the inability of the canonical DNA replication machinery to maintain the DNA at chromosome ends. Shelterin solves this problem by recruiting two enzymes that can replenish the lost telomeric repeats: telomerase and CST-Polα/primase. How shelterin accomplishes these critical tasks is reviewed here.