title: Functional multimerization of the human telomerase reverse transcriptase.
abstract: The telomerase enzyme exists as a large complex (approximately 1,000 kDa) in mammals and at minimum is composed of the telomerase RNA and the catalytic subunit telomerase reverse transcriptase (TERT). In Saccharomyces cerevisiae, telomerase appears to function as an interdependent dimer or multimer in vivo (J. Prescott and E. H. Blackburn, Genes Dev. 11:2790-2800, 1997). However, the requirements for multimerization are not known, and it remained unclear whether telomerase exists as a multimer in other organisms. We show here that human TERT (hTERT) forms a functional multimer in a rabbit reticulocyte lysate reconstitution assay and in human cell extracts. Two separate, catalytically inactive TERT proteins can complement each other in trans to reconstitute catalytic activity. This complementation requires the amino terminus of one hTERT and the reverse transcriptase and C-terminal domains of the second hTERT. The telomerase RNA must associate with only the latter hTERT for reconstitution of telomerase activity to occur. Multimerization of telomerase also facilitates the recognition and elongation of substrates in vitro and in vivo. These data suggest that the catalytic core of human telomerase may exist as a functionally cooperative dimer or multimer in vivo.
authors.affiliation: Ontario Cancer Institute/Amgen Institute, Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada. tbeattie@ucalgary.ca
authors.forename: T L
authors.initials: TL
authors.lastname: Beattie
authors.forename: W
authors.initials: W
authors.lastname: Zhou
authors.forename: M O
authors.initials: MO
authors.lastname: Robinson
authors.forename: L
authors.initials: L
authors.lastname: Harrington
mesh_terms: D002384:Catalysis; D004268:DNA-Binding Proteins; D019281:Dimerization; D006801:Humans; D012441:Saccharomyces cerevisiae; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D019098:Telomerase / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; C509186:TERT protein, human; D019098:Telomerase