Human RPA is an essential telomerase processivity factor for maintaining telomeres.

ABSTRACT: Telomerase counteracts telomere shortening by repeatedly adding DNA repeats to chromosome ends. We identified the replication protein A (RPA) heterotrimer as a telomerase processivity factor critical for telomere maintenance. RPA stimulates telomerase processivity in vitro, and AlphaFold modeling predicts that RPA engages a telomerase surface distinct from the one bound by the shelterin subunit TPP1. Guided by these predictions, we engineered separation-of-function telomerase reverse transcriptase (TERT) mutants and found that the loss of RPA-mediated stimulation impairs telomere elongation, even when TPP1-POT1-mediated stimulation remains intact. Furthermore, short-telomere disease-associated TERT mutations reduce RPA-dependent telomerase stimulation, revealing a mechanistic link between

SUBMITTER: Agrawal S 

PROVIDER: S-EPMC12640109 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature