Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA

doi:10.1038/nsmb.1777

. 2010 Apr;17(4):513-8.

doi: 10.1038/nsmb.1777. Epub 2010 Mar 28.

Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA

Meghan Mitchell¹, Andrew Gillis, Mizuko Futahashi, Haruhiko Fujiwara, Emmanuel Skordalakes

Affiliations

PMID: 20357774
DOI: 10.1038/nsmb.1777

Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA

Meghan Mitchell et al. Nat Struct Mol Biol. 2010 Apr.

. 2010 Apr;17(4):513-8.

doi: 10.1038/nsmb.1777. Epub 2010 Mar 28.

Authors

Meghan Mitchell¹, Andrew Gillis, Mizuko Futahashi, Haruhiko Fujiwara, Emmanuel Skordalakes

Affiliation

¹ Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania, USA.

PMID: 20357774
DOI: 10.1038/nsmb.1777

Abstract

Telomerase is a specialized DNA polymerase that extends the 3' ends of eukaryotic linear chromosomes, a process required for genomic stability and cell viability. Here we present the crystal structure of the active Tribolium castaneum telomerase catalytic subunit, TERT, bound to an RNA-DNA hairpin designed to resemble the putative RNA-templating region and telomeric DNA. The RNA-DNA hybrid adopts a helical structure, docked in the interior cavity of the TERT ring. Contacts between the RNA template and motifs 2 and B' position the solvent-accessible RNA bases close to the enzyme active site for nucleotide binding and selectivity. Nucleic acid binding induces rigid TERT conformational changes to form a tight catalytic complex. Overall, TERT-RNA template and TERT-telomeric DNA associations are remarkably similar to those observed for retroviral reverse transcriptases, suggesting common mechanistic aspects of DNA replication between the two families of enzymes.

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[1] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6 - PubMed

[2] Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1222-6 - PubMed

[3] Mol Cell Biol. 2010 Jan;30(2):447-59 - PubMed

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[10] Genes Dev. 1995 Sep 15;9(18):2214-26 - PubMed

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Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA

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Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA

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