Identification of human telomerase assembly inhibitors enabled by a novel method to produce hTERT.

ABSTRACT: Telomerase is the enzyme that maintains the length of telomeres. It is minimally constituted of two components: a core reverse transcriptase protein (hTERT) and an RNA (hTR). Despite its significance as an almost universal cancer target, the understanding of the structure of telomerase and the optimization of specific inhibitors have been hampered by the limited amount of enzyme available. Here, we present a breakthrough method to produce unprecedented amounts of recombinant hTERT and to reconstitute human telomerase with purified components. This system provides a decisive tool to identify regulators of the assembly of this ribonucleoprotein complex. It also enables the large-scale screening of small-molecules capable to interfere with telomerase assembly. Indeed, it has allowed us to ide

SUBMITTER: Kellermann G 

PROVIDER: S-EPMC4551907 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature