Structure of Telomerase with Telomeric DNA. Cell 2018 May 17;173(5):1179-1190.e13
Date
05/19/2018Pubmed ID
29775593Pubmed Central ID
PMC5995583DOI
10.1016/j.cell.2018.04.038Scopus ID
2-s2.0-85046691882 (requires institutional sign-in at Scopus site) 131 CitationsAbstract
Telomerase is an RNA-protein complex (RNP) that extends telomeric DNA at the 3' ends of chromosomes using its telomerase reverse transcriptase (TERT) and integral template-containing telomerase RNA (TER). Its activity is a critical determinant of human health, affecting aging, cancer, and stem cell renewal. Lack of atomic models of telomerase, particularly one with DNA bound, has limited our mechanistic understanding of telomeric DNA repeat synthesis. We report the 4.8 Å resolution cryoelectron microscopy structure of active Tetrahymena telomerase bound to telomeric DNA. The catalytic core is an intricately interlocked structure of TERT and TER, including a previously structurally uncharacterized TERT domain that interacts with the TEN domain to physically enclose TER and regulate activity. This complete structure of a telomerase catalytic core and its interactions with telomeric DNA from the template to telomere-interacting p50-TEB complex provides unanticipated insights into telomerase assembly and catalytic cycle and a new paradigm for a reverse transcriptase RNP.
Author List
Jiang J, Wang Y, Sušac L, Chan H, Basu R, Zhou ZH, Feigon JAuthor
Yaqiang Wang PhD, MS Assistant Professor in the Biophysics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Catalytic DomainCryoelectron Microscopy
DNA
Humans
Models, Molecular
Nucleic Acid Conformation
Protein Binding
Protein Subunits
Tartrate-Resistant Acid Phosphatase
Telomerase
Telomere
Telomere-Binding Proteins
Tetrahymena thermophila
