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Duplication and functional specialization of the telomere-capping protein Cdc13 in Candida species.

TitleDuplication and functional specialization of the telomere-capping protein Cdc13 in Candida species.
Publication TypeJournal Article
Year of Publication2013
AuthorsLue NF, Chan J
JournalJ Biol Chem
Volume288
Issue40
Pagination29115-23
Date Published2013 Oct 04
ISSN1083-351X
KeywordsBase Sequence, Candida, DNA, Fungal, Evolution, Molecular, Fungal Proteins, Gene Duplication, Glycerol, Models, Biological, Protein Binding, Protein Multimerization, Protein Structure, Tertiary, Telomere, Telomere Homeostasis, Telomere-Binding Proteins
Abstract

The budding yeast G-tail binding complex CST (Cdc13-Stn1-Ten1) is crucial for both telomere protection and replication. Previous studies revealed a family of Cdc13 orthologues (Cdc13A) in Candida species that are unusually small but are nevertheless responsible for G-tail binding and the regulation of telomere lengths and structures. Here we report the identification and characterization of a second family of Cdc13-like proteins in the Candida clade, named Cdc13B. Phylogenetic analysis and sequence alignment indicate that Cdc13B probably arose through gene duplication prior to Candida speciation. Like Cdc13A, Cdc13B appears to be essential. Deleting one copy each of the CDC13A and CDC13B genes caused a synergistic effect on aberrant telomere elongation and t-circle accumulation, suggesting that the two paralogues mediate overlapping and nonredundant functions in telomere regulation. Interestingly, Cdc13B utilizes its C-terminal OB-fold domain (OB4) to mediate self-association and binding to Cdc13A. Moreover, the stability of the heterodimer is evidently greater than that of either homodimer. Both the Cdc13 A/A homodimer and A/B heterodimer, but not the B/B homodimer, recognized the telomere G-tail repeat with high affinity and sequence specificity. Our results reveal novel evolutionary elaborations of the G-tail-binding protein in Saccharomycotina yeast, suggesting a drastic remodeling of CDC13 that entails gene duplication, fusion, and functional specialization. The repeated and independent duplication of G-tail-binding proteins such as Cdc13 and Pot1 hints at the evolutionary advantage of having multiple G-tail-binding proteins.

DOI10.1074/jbc.M113.506519
Alternate JournalJ Biol Chem
PubMed ID23965999
PubMed Central IDPMC3790010
Grant ListR01 GM062631 / GM / NIGMS NIH HHS / United States
GM062631 / GM / NIGMS NIH HHS / United States

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