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A physical and functional constituent of telomerase anchor site.

TitleA physical and functional constituent of telomerase anchor site.
Publication TypeJournal Article
Year of Publication2005
AuthorsLue NF
JournalJ Biol Chem
Volume280
Issue28
Pagination26586-91
Date Published2005 Jul 15
ISSN0021-9258
KeywordsAmino Acid Motifs, Animals, Base Sequence, Binding Sites, Blotting, Western, Catalytic Domain, Cross-Linking Reagents, DNA, DNA Primers, Escherichia coli, Euplotes, Fungal Proteins, Gene Deletion, In Vitro Techniques, Models, Statistical, Molecular Sequence Data, Mutation, Oligonucleotides, Plasmids, Point Mutation, Protein Structure, Tertiary, RNA, Saccharomyces cerevisiae, Telomerase, Telomere, Tetrahymena
Abstract

Telomerase is a ribonucleoprotein reverse transcriptase responsible for the maintenance of one strand of the telomere terminal repeats. It consists minimally of a catalytic protein component (TERT) and an RNA subunit that provides the template. Compared with prototypical reverse transcriptases, telomerase is unique in possessing a DNA binding domain (anchor site) that is distinct from the catalytic site. Yeast TERT mutants bearing deletion or point mutations in an N-terminal domain (known as N-GQ) were found to be selectively impaired in extending primers that form short hybrids with telomerase RNA. The mutants also suffered a significant loss of repeat addition processivity but displayed an enhancement in nucleotide addition processivity. Furthermore, the mutants manifested altered primer utilization properties for oligonucleotides containing non-telomeric residues in the 5'-region. Cross-linking studies indicate that the N-GQ domain physically contacts the 5'-region of the DNA substrate in the context of a telomerase-telomere complex. Together, these results implicate the N-GQ domain of TERT as a physical and functional constituent of the telomerase anchor site. Coupled with previous genetic analysis, our data confirm that anchor site interaction is indeed important for telomerase function in vivo.

DOI10.1074/jbc.M503028200
Alternate JournalJ Biol Chem
PubMed ID15905172
PubMed Central IDPMC1237055
Grant ListR01 GM062631 / GM / NIGMS NIH HHS / United States

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