DNA-binding determinants and cellular thresholds for human telomerase repeat addition processivity.

ABSTRACT: The reverse transcriptase telomerase adds telomeric repeats to chromosome ends. Purified human telomerase catalyzes processive repeat synthesis, which could restore the full ~100 nucleotides of (T₂AG₃)_n lost from replicated chromosome ends as a single elongation event. Processivity inhibition is proposed to be a basis of human disease, but the impacts of different levels of processivity on telomere maintenance have not been examined. Here, we delineate side chains in the telomerase active-site cavity important for repeat addition processivity, determine how they contribute to duplex and single-stranded DNA handling, and test the cellular consequences of partial or complete loss of repeat addition processivity for telomere maintenance. Biochemical findings o

SUBMITTER: Wu RA 

PROVIDER: S-EPMC5494469 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature