Putative Telomere-Recruiting Domain in the Catalytic Subunit of Human Telomerase

Abstract

Telomerase, the enzyme that elongates telomeres, is essential to maintain telomere length and to immortalize most cancer cells. However, little is known about the regulation of this enzyme in higher eukaryotes. We previously described a domain in the hTERT telomerase catalytic subunit that is essential for telomere elongation and cell immortalization in vivo but dispensable for catalytic activity in vitro. Here, we show that fusions of hTERT containing different mutations in this domain to the telomere binding protein hTRF2 redirected the mutated hTERT to telomeres and rescued its in vivo functions. We suggest that this domain posttranscriptionally regulates telomerase function by targeting the enzyme to telomeres.

ACKNOWLEDGMENTS

We thank members of the Counter laboratory for advice, Danny Lew for critical review of the manuscript, and Corinne Linardic and Diane Downie for technical assistance. C.M.C. is especially grateful to Silvia Bacchetti for review of the manuscript and her continued support, guidance, and insight.

This work was supported by NIH grant CA82481. B.N.A. is supported by a Department of Defense Breast Cancer Research Pre-Doctoral Fellowship. C.M.C. is a Leukemia and Lymphoma Scholar.