The telomerase complex and its components. The enzyme telomerase reverse transcriptase (TERT), its RNA component (TERC), the protein dyskerin, and other associated proteins (NHP2, NOP10, and GAR1) are shown. Telomerase catalytically adds TTAGGG hexameric nucleotide repeats to the 3′-hydroxyl end of the telomeric leading strand, using a specific sequence in the RNA component as the template. TERT contains three major domains: the N-terminal region, the reverse-transcriptase motifs, and the C-terminal region, all containing evolutionarily conserved motifs. TERC contains 451 nucleotides in seven conserved regions (CR1 through CR7), including the template (CR1), and an H/ACA box, a hairpin nucleotide sequence characteristic of a class of small nucleolar RNAs involved in RNA processing. Reprinted with permission from Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009;361:2353–2365.