Altered Nucleotide Insertion Mechanisms of Disease-Associated TERT Variants.

ABSTRACT: Telomere biology disorders (TBDs) are a spectrum of diseases that arise from mutations in genes responsible for maintaining telomere integrity. Human telomerase reverse transcriptase (hTERT) adds nucleotides to chromosome ends and is frequently mutated in individuals with TBDs. Previous studies have provided insight into how relative changes in hTERT activity can lead to pathological outcomes. However, the underlying mechanisms describing how disease-associated variants alter the physicochemical steps of nucleotide insertion remain poorly understood. To address this, we applied single-turnover kinetics and computer simulations to the Tribolium castaneum TERT (tcTERT) model system and characterized the nucleotide insertion mechanisms of six disease-associated variants. Each variant h

SUBMITTER: Welfer GA 

PROVIDER: S-EPMC9957172 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature