Interaction hub critical for telomerase recruitment and primer-template handling for catalysis.

ABSTRACT: Telomerase processively adds telomeric DNA repeats to chromosome ends using catalytic protein subunit TERT and a template on its RNA subunit TR. Mammalian telomerase is recruited to telomeres by the TEL patch and NOB regions of shelterin component TPP1. Recent cryo-EM structures of human telomerase reveal that a composite TERT TEN-(IFD-TRAP) domain interacts with TPP1. Here, we generate TERT mutants to demonstrate that a three-way TEN-(IFD-TRAP)-TPP1 interaction is critical for telomerase recruitment to telomeres and processive telomere repeat addition. Single mutations of IFD-TRAP at its interface with TR or the DNA primer impair telomerase catalysis. We further reveal the importance of TERT motif 3N and TEN domain loop ⁹⁹FGF¹⁰¹ in telomerase action. Finally, we demo

SUBMITTER: Padmanaban S 

PROVIDER: S-EPMC10055720 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature