| Rap1 in Candida albicans: an unusual structural organization and a critical function in suppressing telomere recombination. | |
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MedLine Citation:
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PMID: 20008550 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Rap1 (repressor activator protein 1) is a conserved multifunctional protein initially identified as a transcriptional regulator of ribosomal protein genes in Saccharomyces cerevisiae but subsequently shown to play diverse functions at multiple chromosomal loci, including telomeres. The function of Rap1 appears to be evolutionarily plastic, especially in the budding yeast lineages. We report here our biochemical and molecular genetic characterizations of Candida albicans Rap1, which exhibits an unusual, miniaturized domain organization in comparison to the S. cerevisiae homologue. We show that in contrast to S. cerevisiae, C. albicans RAP1 is not essential for cell viability but is critical for maintaining normal telomere length and structure. The rap1 null mutant exhibits drastic telomere-length dysregulation and accumulates high levels of telomere circles, which can be largely attributed to aberrant recombination activities at telomeres. Analysis of combination mutants indicates that Rap1 and other telomere proteins mediate overlapping but nonredundant roles in telomere protection. Consistent with the telomere phenotypes of the mutant, C. albicans Rap1 is localized to telomeres in vivo and recognizes the unusual telomere repeat unit with high affinity and sequence specificity in vitro. The DNA-binding Myb domain of C. albicans Rap1 is sufficient to suppress most of the telomere aberrations observed in the null mutant. Notably, we were unable to detect specific binding of C. albicans Rap1 to gene promoters in vivo or in vitro, suggesting that its functions are more circumscribed in this organism. Our findings provide insights on the evolution and mechanistic plasticity of a widely conserved and functionally critical telomere component. |
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Authors:
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Eun Young Yu; Wei-Feng Yen; Olga Steinberg-Neifach; Neal F Lue |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-12-14 |
Journal Detail:
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Title: Molecular and cellular biology Volume: 30 ISSN: 1098-5549 ISO Abbreviation: Mol. Cell. Biol. Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-02-12 Completed Date: 2010-03-26 Revised Date: 2010-09-02 |
Medline Journal Info:
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Nlm Unique ID: 8109087 Medline TA: Mol Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 1254-68 Citation Subset: IM |
Affiliation:
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Department of Microbiology and Immunology, W. R. Hearst Microbiology Research Center, Weill Medical College of Cornell University, 1300 York Ave., New York, New York 10021, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Base Sequence Binding Sites / genetics Candida albicans / genetics*, growth & development, metabolism* DNA Primers / genetics DNA, Fungal / genetics, metabolism Evolution, Molecular Fungal Proteins / chemistry*, genetics, metabolism* Genes, Fungal Models, Biological Molecular Sequence Data Mutation Phenotype Protein Structure, Tertiary Recombination, Genetic* Saccharomyces cerevisiae Proteins / chemistry, genetics Sequence Homology, Amino Acid Sequence Homology, Nucleic Acid Species Specificity Telomere / genetics*, metabolism* Telomere-Binding Proteins / chemistry*, genetics, metabolism* Transcription Factors / chemistry*, genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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GM-069507/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Primers; 0/DNA, Fungal; 0/Fungal Proteins; 0/RAP1 protein, Candida albicans; 0/RAP1 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; 0/Telomere-Binding Proteins; 0/Transcription Factors |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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