Structures of telomerase subunits provide functional insights

Background: Telomerase continues to generate substantial attention both because of its pivotal roles in cellular proliferation and aging and because of its unusual structure and mechanism. By replenishing telomeric DNA lost during the cell cycle, telomerase overcomes one of the many hurdles facing cellular immortalization. Functionally, telomerase is a reverse transcriptase, and it shares structural and mechanistic features with this class of nucleotide polymerases. Telomerase is a very unusual reverse transcriptase because it remains stably associated with its template and because it reverse transcribes multiple copies of its template onto a single primer in one reaction cycle. Scope of review: Here, we review recent findings that illuminate our understanding of telomerase. Even though the specific emphasis is on structure and mechanism, we also highlight new insights into the roles of telomerase in human biology. General significance: Recent advances in the structural biology of telomerase, including high resolution structures of the catalytic subunit of a beetle telomerase and two domains of a ciliate telomerase catalytic subunit, provide new perspectives into telomerase biochemistry and reveal new puzzles.