Human telomerase specialization for repeat synthesis by unique handling of primer-template duplex.

ABSTRACT: With eukaryotic genome replication, incomplete telomere synthesis results in chromosome shortening and eventual compromise of genome stability. Telomerase counteracts this terminal sequence loss by synthesizing telomeric repeats through repeated cycles of reverse transcription of its internal RNA template. Using human telomerase domain-complementation assays for telomerase reverse transcriptase protein (TERT) and RNA in combination with the first direct footprinting assay for telomerase association with bound DNA, we resolve mechanisms by which TERT domains and RNA motifs direct repeat synthesis. Surprisingly, we find that product-template hybrid is sensed in a length- and sequence-dependent manner to set the template 5' boundary. We demonstrate that the TERT N-terminal (TEN) domain determ

SUBMITTER: Wu RA 

PROVIDER: S-EPMC4194115 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature