Telomerase Times Two

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Science  29 Mar 2013:
Vol. 339, Issue 6127, pp. 1499
DOI: 10.1126/science.339.6127.1499-a

In eukaryotes, chromosome ends are capped by telomeres: protein-DNA complexes that are essential for genomic stability. Telomere length is maintained by the enzyme telomerase, which comprises an RNA subunit (TER), that contains the template for synthesis of telomeric DNA repeats and a protein subunit, telomerase reverse transcriptase (TERT), that catalyzes nucleotide addition. In contrast to macromolecular machines such as the ribosome and RNA polymerase, structural information on telomerase has been limited to subdomains, and this has hindered understanding of its function. Debate continues over whether telomerase functions as a monomer or a dimer. To resolve this debate, Sauerwald et al. obtained sufficient quantities of purified, active human telomerase for biochemical, structural, and functional studies. Biochemical and functional data showed that telomerase functions as a dimer. It binds two telomeric DNA substrates, and two functional TERT subunits are required for activity. A structure determined by single-particle electron microscopy (EM) at better than 30 Å resolution revealed a bi-lobal architecture with a size consistent with a homodimer. Gold-labeling and fitting of a high-resolution structure of a TERT subunit into the EM density provided further insight into the architecture of telomerase. Future higher-resolution structures will probably give an even more increasingly detailed view of telomerase function.

Nat. Struct. Mol. Biol. 20, 10.1038/nsmb.2530 (2013).

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