A modified model for translocation events of processive nucleotide and repeat additions by the recombinant telomerase

Telomerase is a unique reverse transcriptase that extends the single-stranded 3' overhangs of telomeres by copying a short template sequence within the integral RNA component of the enzyme. It shows processive nucleotide and repeat addition activities, which are realized via two types of movements: translocation of the DNA:RNA hybrid away from the active site following each nucleotide addition and translocation of the 3' end of the DNA primer relative to the RNA template after each round of repeat synthesis. Here, a model is presented to describe these two types of translocation events by the recombinant Tetrahymena telomerase, via the modification of the model that has been proposed recently. Using the present model, the dynamics of the dissociation of the DNA primer from the telomerase and the dynamics of the disruption of the DNA:RNA hybrid and then repositioning of the product 3' end to the beginning of the template are studied quantitatively. Their effects on the repeat addition processivity are theoretically studied. The theoretical results are in agreement with the available experimental data. (C) 2010 Elsevier B.V. All rights reserved.