Adding to the ends: what makes telomerase processive and how important is it?

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Abstract
Telomerase is a cellular reverse transcriptase responsible for telomere maintenance in most organisms. It does so by adding telomere repeats onto pre‐existing ends using an integral RNA component as template. Compared to “prototypical” reverse transcriptases, telomerase is unique in being able to repetitively copy a short templating RNA segment, thus adding multiple copies of the repeat to the DNA substrate following a single binding event. This uniquely processive property hints at the intricate conformational alterations that the enzyme must choreograph during its reaction cycles. Recent studies have identified distinct structural elements within both the RNA and protein components of telomerase that modulate enzyme processivity. Pharmacological and genetic analysis suggest that telomerase processivity is a significant determinant of telomere length. Because telomere maintenance and the lack thereof have been linked to tumor progression and aging, further investigation of telomerase processivity may lead to novel medical intervention strategies. BioEssays 26:955–962, 2004.