Open AccessFlexibility of telomerase in binding the RNA template and DNA telomeric repeat
Author(s) -
Woo Suk Choi,
Peter J. Weng,
Wei Yang
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2116159118
Subject(s) - telomerase , telomere , dna , rna , computational biology , biology , genetics , flexibility (engineering) , microbiology and biotechnology , gene , statistics , mathematics
Significance Telomerase reverse transcriptase (TERT) has a conserved central cavity near the active site. Using enzymatic and mutagenesis analyses, we provide experimental evidence that an artificially looped-out telomeric repeat in the DNA primer can be transiently accommodated in the cavity ofTribolium castaneum (tc TERT). Kinetically,tc TERT requires a minimum of 4 bp between the RNA template and DNA primer for efficient DNA synthesis. An RNA duplex downstream of the RNA-template region after a flexible linker enhances the efficiency of primer extension bytc TERT. In addition to the peripheral cavities that accommodate looped-out RNA during each telomeric repeat synthesis, the central cavity that can accommodate the looped-out DNA may aid RNA-template translocation between cycles of telomeric repeat synthesis.