The fidelity of human telomerase.

The ribonucleoprotein enzyme telomerase is a RNA dependent DNA polymerase. The function of telomeres is mediated by the proteins which bind telomeric repeats. The binding of those proteins is sequence specific. We determined the fidelity of the DNA polymerization reaction of human telomerase in order to understand the origin of non-canonical telomeric repeats in human telomeres and to gain insight into the reaction mechanism of telomerase. By cloning and sequencing a large number of in vitro generated telomeric repeats we found the error rate for human telomerase to be approximately 2 x 10(-3) per nucleotide or one non-TTAGGG repeat for every 100 TTAGGG repeats. All the nucleotide changes observed were A --> C changes for a positional error rate of 1.2 x 10(-2). All the other positions had no observed errors for a positional error rate no greater than 1.2 x 10(-3).