The Unmasking of Telomerase

Telomerase is a ribonucleoprotein complex that reverse transcribes a portion of its RNA subunit during the synthesis of G-rich DNA at the 3′ end of each chromosome in most eukaryotes. This activity compensates for the inability of the normal DNA replication machinery to fully replicate chromosome termini. The roles of telomerase in cellular immortality and tumor biology have catalyzed a significant interest in this unusual polymerase. Recently the first structures of two domains, the CR4/CR5 and pseudoknot, of human telomerase RNA (hTR) were reported, offering a structural basis for interpreting biochemical studies and possible roles of hTR mutations in human diseases. Structures of the stem II and stem IV domains of Tetrahymena thermophila TR as well as the N-terminal domain of the T. thermophila telomerase reverse transcriptase have also been determined. These studies complement previous biochemical studies, providing rich insight into the structural basis for telomerase activity.