National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM048123
米国
National Science Foundation (NSF, United States)
MCB1517625
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM071940
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM007185
米国
National Institutes of Health/Office of the Director
1S10OD018111
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
1U24GM116792
米国
National Science Foundation (NSF, United States)
DBI-1338135
米国
National Science Foundation (NSF, United States)
DMR-1548924
米国
American Heart Association
14POST18870059
米国
引用
ジャーナル: Cell / 年: 2018 タイトル: Structure of Telomerase with Telomeric DNA. 著者: Jiansen Jiang / Yaqiang Wang / Lukas Sušac / Henry Chan / Ritwika Basu / Z Hong Zhou / Juli Feigon / 要旨: 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 ...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.