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The telomeric Cdc13-Stn1-Ten1 complex regulates RNA pol II transcription

ABSTRACT: Specialized telomeric proteins have an essential role in maintaining genome stability through chromosome end protection and telomere length regulation. In the yeast Saccharomyces cerevisiae, the evolutionary conserved CST complex, composed of the Cdc13, Stn1 and Ten1 proteins, largely contributes to these functions. Here, we report the existence of genetic interactions between TEN1 and several genes coding for transcription regulators. Molecular assays confirmed this novel function of Ten1 and further established that it regulates the occupancies of RNA polymerase II and the Spt5 elongation factor within transcribed genes. Since Ten1, but also Cdc13 and Stn1, were found to physically associate with Spt5, we propose that Spt5 represents the target of CST in transcription regulation. Moreover, CST physically associated with Hmo1, previously shown to mediate the architecture of S phase-transcribed genes. The fact that, genome-wide, the promoters of genes down-regulated in the ten1-31 mutant are prefentially bound by Hmo1, leads us to propose a potential role for CST in synchronizing transcription with replication fork progression following head-on collisions. The present finding of the existence of extra-telomeric functions for Ten1 in the regulation of RNA polymerase II in cooperation with Stn1 and Cdc13 has profound repercussions on future studies both on telomeric and transcription pathways.

ORGANISM(S): Saccharomyces cerevisiae

PROVIDER: GSE120296 | GEO | 2019/04/08

REPOSITORIES: GEO

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The telomeric Cdc13-Stn1-Ten1 complex regulates RNA pol II transcription

Project description:The telomeric Cdc13-Stn1-Ten1 complex regulates RNA pol II transcription

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Stn1 S74 phosphorylation - Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions by conventional DNA polymerases and telomerase, though the regulation of this process is not fully understood

Project description:Publication abstract: Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions by conventional DNA polymerases and telomerase, though the regulation of this process is not fully understood. Telomere replication requires (C)-Stn1-Ten1, a telomere ssDNA-binding complex that is homologous to RPA. Here, we show that the evolutionarily conserved phosphatase Ssu72 is responsible for terminating the cycle of telomere replication in fission yeast. Ssu72 controls the recruitment of Stn1 to telomeres by regulating Stn1 phosphorylation at S74, a residue that lies within the conserved OB fold domain. Consequently, ssu72Δ mutants are defective in telomere replication and exhibit long 3′ overhangs, which are indicative of defective lagging strand DNA synthesis. We also show that hSSU72 regulates telomerase activation in human cells by controlling the recruitment of hSTN1 to telomeres. Thus, in this study, we demonstrate a previously unknown yet conserved role for the phosphatase SSU72, whereby this enzyme controls telomere homeostasis by activating lagging strand DNA synthesis, thus terminating the cycle of telomere replication. Summary of MS experiment: Stn1 protein was tagged in the C-terminus with 13-myc tag and purified by immunoprecipitation. The purified extracts were separated by SDS-PAGE and proteins between 63 and 75 kDa were excised and in-gel digested. Tryptic peptides were analyzed by LC-MS/MS using an AB Sciex TripleTOF 6600 mass spectrometer upon separation by nanoLC-MS using an Ekspert 425 nanoLC with cHiPLC. Stn1 protein was identified with 48% of coverage and Serine-74 was found to be phosphorylated.

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2017-05-11 | PXD006074 | Pride

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