ArticleJournal of molecular biology2008
Structural and functional studies of the Rap1 C-terminus reveal novel separation-of-function mutants.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Unwrap RAP1's Mystery at Kinetoplastid Telomeres.Biomolecules · 2024Review
- DNA binding modes influence Rap1 activity in the regulation of telomere length and MRX functions at DNA ends.Nucleic acids research · 2020Article
- Trypanosoma brucei RAP1 Has Essential Functional Domains That Are Required for Different Protein Interactions.mSphere · 2020Article
- Repression of Divergent Noncoding Transcription by a Sequence-Specific Transcription Factor.Molecular cell · 2018Article
- Shepherding DNA ends: Rif1 protects telomeres and chromosome breaks.Microbial cell (Graz, Austria) · 2018Review
- Telomere shortening triggers a feedback loop to enhance end protection.Nucleic acids research · 2017Article
- Genome-wide Mapping of Protein-DNA Interactions with ChEC-seq in Saccharomyces cerevisiae.Journal of visualized experiments : JoVE · 2017Article
- Identification of a transcriptional activation domain in yeast repressor activator protein 1 (Rap1) using an altered DNA-binding specificity variant.The Journal of biological chemistry · 2017Article
- ChEC-seq kinetics discriminates transcription factor binding sites by DNA sequence and shape in vivo.Nature communications · 2015Article
- The Ku subunit of telomerase binds Sir4 to recruit telomerase to lengthen telomeres in S. cerevisiae.eLife · 2015Article
- Telomere DNA recognition in Saccharomycotina yeast: potential lessons for the co-evolution of ssDNA and dsDNA-binding proteins and their target sites.Frontiers in genetics · 2015Review
- End-joining inhibition at telomeres requires the translocase and polySUMO-dependent ubiquitin ligase Uls1.The EMBO journal · 2013Article
- The orientation of the C-terminal domain of the Saccharomyces cerevisiae Rap1 protein is determined by its binding to DNA.Nucleic acids research · 2012Article
- Telomerase and telomere-associated proteins: structural insights into mechanism and evolution.Structure (London, England : 1993) · 2012Review
- A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms.Nature structural & molecular biology · 2011Article
- Characterization of the yeast telomere nucleoprotein core: Rap1 binds independently to each recognition site.The Journal of biological chemistry · 2010Article
- Rap1 in Candida albicans: an unusual structural organization and a critical function in suppressing telomere recombination.Molecular and cellular biology · 2010Article
- Inactivation of the Sas2 histone acetyltransferase delays senescence driven by telomere dysfunction.The EMBO journal · 2010Article
- Plasticity of telomere maintenance mechanisms in yeast.Trends in biochemical sciences · 2010Review
- The association of yKu with subtelomeric core X sequences prevents recombination involving telomeric sequences.Genetics · 2009Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The yeast Rap1 protein plays an important role in transcriptional silencing and in telomere length homeostasis. Rap1 mediates silencing at the HM loci and at telomeres by recruiting the Sir3 and Sir4 proteins to chromatin via a Rap1 C-terminal domain, which also recruits the telomere length regulators, Rif1 and Rif2. We report the 1.85 A resolution crystal structure of the Rap1 C-terminus, which adopts an all-helical fold with no structural homologues. The structure was used to engineer surface mutations in Rap1, and the effects of these mutations on silencing and telomere length regulation were assayed in vivo. Our surprising finding was that there is no overlap between mutations affecting mating-type and telomeric silencing, suggesting that Rap1 plays distinct roles in silencing at the silent mating-type loci and telomeres. We also found novel Rap1 phenotypes and new separation-of-function mutants, which provide new tools for studying Rap1 function. Yeast two-hybrid studies were used to determine how specific mutations affect recruitment of Sir3, Rif1, and Rif2. A comparison of the yeast two-hybrid and functional data reveals patterns of protein interactions that correlate with each Rap1 phenotype. We find that Sir3 interactions are important for telomeric silencing, but not mating type silencing, and that Rif1 and Rif2 interactions are important in different subsets of telomeric length mutants. Our results show that the role of Rap1 in silencing differs between the HM loci and the telomeres and offer insight into the interplay between HM silencing, telomeric silencing, and telomere length regulation. These findings suggest a model in which competition and multiple recruitment events modulate silencing and telomere length regulation.
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