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Telomerase regulatory subunit Est3 in two Candida species physically interacts with the TEN domain of TERT and telomeric DNA.

TitleTelomerase regulatory subunit Est3 in two Candida species physically interacts with the TEN domain of TERT and telomeric DNA.
Publication TypeJournal Article
Year of Publication2011
AuthorsYen W-F, Chico L, Lei M, Lue NF
JournalProc Natl Acad Sci U S A
Volume108
Issue51
Pagination20370-5
Date Published2011 Dec 20
ISSN1091-6490
KeywordsAlleles, Bacterial Proteins, Candida, Candida albicans, Cross-Linking Reagents, DNA, DNA-Binding Proteins, Models, Genetic, Molecular Conformation, Mutation, Protein Structure, Tertiary, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Species Specificity, Telomerase, Telomere
Abstract

The yeast telomerase regulatory protein Est3 is required for telomere maintenance in vivo, and shares intriguing structural and functional similarities with the mammalian telomeric protein TPP1. Here we report our physical and functional characterizations of Est3 homologues from Candida parapsilosis and Lodderomyces elongisporus, which bear unique N- and C-terminal tails in addition to a conserved central OB fold. We show that these Est3 homologues form stable complexes with the TEN domain of telomerase reverse transcriptase. Efficient complex formation requires both the N- and C-terminal tails, as well as conserved OB fold residues of Est3. Other Est3 homologues devoid of the tails failed to interact strongly with the cognate TEN domains. Remarkably, the C. parapsilosis Est3 alone exhibits no appreciable DNA-binding activity, but can be crosslinked to telomeric DNA in the presence of the TEN domain. A conserved basic residue on the putative DNA-binding surface of CpEst3 is required for efficient crosslinking. Mutating the equivalent residue in Candida albicans Est3 caused telomere attrition. We propose that interaction with the TEN domain unmasks a functionally important nucleic acid-binding activity in Est3. Our findings provide insights on the mechanisms and evolution of a widely conserved and functionally critical telomeric/telomerase component.

DOI10.1073/pnas.1017855108
Alternate JournalProc Natl Acad Sci U S A
PubMed ID21685334
PubMed Central IDPMC3251127
Grant ListR01 GM069507 / GM / NIGMS NIH HHS / United States
GM-069507 / GM / NIGMS NIH HHS / United States
/ / Howard Hughes Medical Institute / United States

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