Single-Molecule FRET Reveals the Folding Dynamics of the Human Telomerase RNA Pseudoknot Domain

摘要

Telomerase-catalyzed synthesis of telomere DNA provides the foundation for the DNA-protein structures known as telomeres. Telomeres are required to evade DNA processing that may result in nucleolytic degradation and fusion of linear chromosomes. Human telomeres are maintained by a complex of human telomerase reverse transcriptase (hTERT), human telomerase RNA (hTR), and several additional proteins. hTR provides the template sequence for hTERT during a novel reverse transcription reaction that produces short telomere DNA repeat sequences. Additionally, hTR provides a flexible scaffold for the assembly and function of telomerase-associated proteins and has recently been suggested to contribute to hTERT catalysis. Many pathogenic mutations have been mapped to hTR; however the precise mechanisms of how these mutations cause disease remain unclear.