Telomere maintenance, function and evolution: the yeast paradigm

Teixeira, Maria Teresa; Gilson, Éric

doi:10.1007/s10577-005-0999-0

Cited by 60 publications

(52 citation statements)

References 119 publications

(117 reference statements)

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“…First, we hypothesize that in the ancestral budding yeast, Rap1 was tethered to telomeres through an interaction between its RCT domain and TRF2 (as in humans) and mediated a crucial telomere protection function. In accordance with earlier proposals (29,49), we imagine that multiple telomerase RNA template mutations were somehow fixed in descendants of the yeast. The corresponding telomere sequence alterations in turn caused a major remodeling of the telomere nucleoprotein complex.…”

Section: Discussionsupporting

confidence: 75%

“…Interestingly, while the telomeres in many yeast (e.g., Zygomycota, Basidiomycota, and Eurotiomycetes) and metazoan species conform to the canonical TTAGGG repeat unit, the telomeres of the Saccharomycotina subphylum of budding yeast (including Saccharomyces, Kluyveromyces, Dabromyces, and Candida spp.) have been found to exhibit extraordinary sequence diversity (49). The length of the repeat unit ranges from 8 to 25 bp, and the repeat sequence can be rather degenerate.…”

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confidence: 99%

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Rap1 in Candida albicans: an Unusual Structural Organization and a Critical Function in Suppressing Telomere Recombination

Yen

Steinberg-Neifach

et al. 2010

Molecular and Cellular Biology

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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.Multifunctional Rap1 (repressor activator protein 1) was first discovered in the budding yeast Saccharomyces cerevisiae as a positive transcriptional regulator of multiple growth-related genes such as the ribosomal protein genes (23). Other studies identified Rap1 as the major double-strand telomere repeat binding protein in S. cerevisiae and to be essential for maintaining telomere length and structural integrity (5, 10). Upon further analysis, Rap1 was recognized as a key component of the mating-type silencer and shown to be required for transcriptional silencing (7,43,44). These disparate observations raised fascinating questions concerning the mechanisms whereby a single protein participates in diverse functions at distinct chromosomal locations. The identification of Rap1 homologues in humans and the fission yeast resulted in yet more surprises (25,29). Both homologues were shown to be telomere-associated proteins required for proper telomere length regulation. However, instead of binding DNA directly, human and Schizosaccharomyces pombe Rap1 proteins were recruited to telomeres through interaction with other telomere proteins such as TRF2 and Taz1. Moreover, there is no evidence that the human and S. pombe proteins are involved in transcriptional regulation. Thus, although th...

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Section: Discussionsupporting

confidence: 75%

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confidence: 99%

Rap1 in Candida albicans: an Unusual Structural Organization and a Critical Function in Suppressing Telomere Recombination

Yen

Steinberg-Neifach

et al. 2010

Molecular and Cellular Biology

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“…sequence previously reported in the literature (19,59)). Our EMSA experiments led to ambiguous results.…”

Section: Discussionmentioning

confidence: 88%

Tay1 Protein, a Novel Telomere Binding Factor from Yarrowia lipolytica

Kramara

Willcox

Gunišová

et al. 2010

Journal of Biological Chemistry

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Inspection of the complete genome of the yeastAll linear chromosomes possess two telomeres, specialized nucleoprotein structures that protect the genomic integrity by providing a solution to the "end-replication problem," prevent inappropriate action of DNA repair machinery, and mask the chromosomal ends against degradation by nucleases (1). Human telomeric chromatin is composed of about 200 different proteins (2) playing various roles at chromosomal termini, including transcription and packaging of TERRA RNA (telomere repeat containing RNA) (3, 4) or in the organization of higher order telomeric chromatin structure (5). Telomere protection is facilitated in large part by proteins that specifically bind to either single-stranded (ss) or double-stranded (ds) regions of telomeric DNA (6). The telomere-binding proteins form a cap that protects chromosome ends against activities of DNA repair machinery (7). Whereas the G-rich 3Ј ssDNA telomeric overhang is bound by oligosaccharide binding-fold-containing proteins like Pot1p (8) and Cdc13p (9), the duplex region of the telomere is associated with dsDNAbinding proteins containing a Myb/SANT domain. These include mammalian TRF1 and TRF2 proteins (10), budding yeast proteins Rap1 and Tbf1 (11,12), and the fission yeast telomeric proteins Taz1 (13) and Tbf1 (14). The telomeric proteins protect telomeres at two levels. First, proteins such as TRF2 and Taz1p mediate formation of a telomeric loop and hide the 3Ј telomeric overhang into the ds region of the telomere, thus, preventing inappropriate recognition by the DNA repair machinery (15,16). Second, the telomere-binding proteins associate with other components and form a special nucleoprotein structure termed shelterin (10). In addition, telomere-binding proteins are important for recruitment of telomerase and other enzymes involved in telomere maintenance at chromosomal ends (7). The central role of telomerebinding proteins in protecting chromosomal ends and regulating DNA transactions, including telomerase-dependent elongation and recombination, underlines the importance of investigating their biochemical properties.

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“…Most telomerase studies have involved Tetrahymena thermophila, Saccharomyces cerevisiae, Schizosaccharomyces pombe, mice, or cultured human cells. Less-intensively studied but important additional model systems include other ciliates, yeasts, vertebrates and also plants (Collins 1999;Teixeira and Gilson 2005;Watson and Riha 2010;Cifuentes-Rojas et al 2011;Yu 2012).…”

Section: Introductionmentioning

confidence: 99%

Biogenesis of telomerase ribonucleoproteins

Egan

Collins

2012

RNA

157

168

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Telomerase adds simple-sequence repeats to the ends of linear chromosomes to counteract the loss of end sequence inherent in conventional DNA replication. Catalytic activity for repeat synthesis results from the cooperation of the telomerase reverse transcriptase protein (TERT) and the template-containing telomerase RNA (TER). TERs vary widely in sequence and structure but share a set of motifs required for TERT binding and catalytic activity. Species-specific TER motifs play essential roles in RNP biogenesis, stability, trafficking, and regulation. Remarkably, the biogenesis pathways that generate mature TER differ across eukaryotes. Furthermore, the cellular processes that direct the assembly of a biologically functional telomerase holoenzyme and its engagement with telomeres are evolutionarily varied and regulated. This review highlights the diversity of strategies for telomerase RNP biogenesis, RNP assembly, and telomere recruitment among ciliates, yeasts, and vertebrates and suggests common themes in these pathways and their regulation.

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Telomere maintenance, function and evolution: the yeast paradigm

Cited by 60 publications

References 119 publications

Rap1 in Candida albicans: an Unusual Structural Organization and a Critical Function in Suppressing Telomere Recombination

Rap1 in Candida albicans: an Unusual Structural Organization and a Critical Function in Suppressing Telomere Recombination

Tay1 Protein, a Novel Telomere Binding Factor from Yarrowia lipolytica

Biogenesis of telomerase ribonucleoproteins

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