Appendix: A Personal Account of the Discovery of Telomerase

Abstract

DID A NEW ENZYME EXIST IN CELLS THAT COULD SYNTHESIZE TELOMERIC DNA?
The molecular features of telomeric DNA were not consistent with any of the properties expected from the models for telomere replication that had become current in the 1970s. In the early 1980s, four lines of evidence led me to think that a new enzyme activity might work on telomeres to elongate them. Each consisted of molecular observations on telomeric DNA that could not be readily explained otherwise.

First, telomeric GGGGTT repeat tracts on minichromosomes in the ciliates Tetrahymena thermophila and Glaucoma chattoni were heterogeneous in length (Blackburn and Gall 1978; Yao et al. 1979; Katzen et al. 1981). Second, telomeric GGGGTT repeat tract DNA was found added to various sequences in ciliate minichromosomes as a result of the process by which new telomeres formed on chromosomes during development of the somatic nucleus. This stage in the ciliate life cycle had an intriguing parallel in the postfertilization phase when maize chromosomes could heal and when Ascarid chromosomes fragmented to form new chromosomes with stable ends. Meng-Chao Yao, working in Martin Gorovsky’s lab and then Joe Gall’s lab, had found such telomeric DNA acquisition for Tetrahymena rDNA minichromosomes, and in my lab at the University of California at Berkeley, we had made similar observations for other, non-rDNA telomeres of the somatic nucleus (Yao et al. 1979; King and Yao 1982; Blackburn et al. 1983).

Simultaneously, David Prescott’s group in Colorado had made the corresponding observation for the telomeres of somatic...