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The CR7 domain point mutation decreases stability and alters a conserved secondary structure thought to be involved in human telomerase RNA accumulation\n                    <jats:italic>in vivo<\/jats:italic>\n                    . We find that pseudoknot constructs containing the conserved elements of the pseudoknot domain are in equilibrium with a hairpin conformation. The solution structure of the wild-type hairpin reveals that it forms a continuous helix containing a novel run of three consecutive U\u22c5U and a U\u22c5C base pairs closed by a pentaloop. The six base pairs unique to the hairpin conformation are phylogenetically conserved in mammals, suggesting that this conformation is also functionally important. The DKC mutation in the pseudoknot domain results in a shift in the equilibrium toward the hairpin form, primarily due to destabilization of the pseudoknot. Our results provide insight into the effect of these mutations on telomerase structure and suggest that the catalytic cycle of telomerase involves a delicate interplay between RNA conformational states, alteration of which leads to the disease state.\n                  <\/jats:p>","DOI":"10.1073\/pnas.242720799","type":"journal-article","created":{"date-parts":[[2003,1,21]],"date-time":"2003-01-21T17:51:47Z","timestamp":1043171507000},"page":"449-454","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":145,"title":["Mutations linked to dyskeratosis congenita cause changes in the structural equilibrium in telomerase RNA"],"prefix":"10.1073","volume":"100","author":[{"given":"Carla A.","family":"Theimer","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry and Molecular Biology Institute, University of California, Los Angeles, CA 90095-1569"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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