title: 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.
authors.affiliation: Departments of Pharmacology and Cancer Biology, Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Blaine N
authors.initials: BN
authors.lastname: Armbruster
authors.forename: Katherine T
authors.initials: KT
authors.lastname: Etheridge
authors.forename: Dominique
authors.initials: D
authors.lastname: Broccoli
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Counter
mesh_terms: D020134:Catalytic Domain; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism*; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D035341:Telomeric Repeat Binding Protein 2; D004247:DNA; D019098:Telomerase