Towards the Mechanism of Yeast Telomere Dynamics

Lustig, Arthur J.

doi:10.1016/j.tcb.2019.01.005

Cited by 8 publications

(6 citation statements)

References 54 publications

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“…The length of the G-overhang exhibits interspecific, intercellular, and interchromosomal variations (10,11). Telomeric DNA is bound by a set of dedicated proteins forming a protective nucleoprotein structure comprising a number of telomere-binding proteins that often exhibit binding specificity (3,12). Examples include the dsDNA-binding protein Rap1 and the G-overhang-binding protein Cdc13 in S. cerevisiae.…”

Section: More Than 80 Years Ago Herman Muller and Barbaramentioning

confidence: 99%

Role of folding kinetics of secondary structures in telomeric G-overhangs in the regulation of telomere maintenance in Saccharomyces cerevisiae

Juríková

Gajarský

Hajikazemi

et al. 2020

Journal of Biological Chemistry

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The ends of eukaryotic chromosomes typically contain a 3′ ssDNA G-rich protrusion (G-overhang). This overhang must be protected against detrimental activities of nucleases and of the DNA damage response machinery and participates in the regulation of telomerase, a ribonucleoprotein complex that maintains telomere integrity. These functions are mediated by DNA-binding proteins, such as Cdc13 in Saccharomyces cerevisiae, and the propensity of G-rich sequences to form various non-B DNA structures. Using CD and NMR spectroscopies, we show here that G-overhangs of S. cerevisiae form distinct Hoogsteen pairing–based secondary structures, depending on their length. Whereas short telomeric oligonucleotides form a G-hairpin, their longer counterparts form parallel and/or antiparallel G-quadruplexes (G4s). Regardless of their topologies, non-B DNA structures exhibited impaired binding to Cdc13 in vitro as demonstrated by electrophoretic mobility shift assays. Importantly, whereas G4 structures formed relatively quickly, G-hairpins folded extremely slowly, indicating that short G-overhangs, which are typical for most of the cell cycle, are present predominantly as single-stranded oligonucleotides and are suitable substrates for Cdc13. Using ChIP, we show that the occurrence of G4 structures peaks at the late S phase, thus correlating with the accumulation of long G-overhangs. We present a model of how time- and length-dependent formation of non-B DNA structures at chromosomal termini participates in telomere maintenance.

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Section: More Than 80 Years Ago Herman Muller and Barbaramentioning

confidence: 99%

Role of folding kinetics of secondary structures in telomeric G-overhangs in the regulation of telomere maintenance in Saccharomyces cerevisiae

Juríková

Gajarský

Hajikazemi

et al. 2020

Journal of Biological Chemistry

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“…Finally, we note that the telomeres of budding yeast are recalcitrant to telomerase-mediated extension unless chromosome ends are in an extendable chromatin conformation 61 , 62 . Indeed, a complex interplay between telomerase and telomere-associated proteins, DNA replication and repair machinery, and the telomere epigenome establishes telomere length homeostasis 63 . A similar mechanism may operate in Arabidopsis.…”

Section: Resultsmentioning

confidence: 99%

Arabidopsis telomerase takes off by uncoupling enzyme activity from telomere length maintenance in space

Barcenilla,

Meyers,

Castillo-González

et al. 2023

Nat Commun

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Spaceflight-induced changes in astronaut telomeres have garnered significant attention in recent years. While plants represent an essential component of future long-duration space travel, the impacts of spaceflight on plant telomeres and telomerase have not been examined. Here we report on the telomere dynamics of Arabidopsis thaliana grown aboard the International Space Station. We observe no changes in telomere length in space-flown Arabidopsis seedlings, despite a dramatic increase in telomerase activity (up to 150-fold in roots), as well as elevated genome oxidation. Ground-based follow up studies provide further evidence that telomerase is induced by different environmental stressors, but its activity is uncoupled from telomere length. Supporting this conclusion, genetically engineered super-telomerase lines with enhanced telomerase activity maintain wildtype telomere length. Finally, genome oxidation is inversely correlated with telomerase activity levels. We propose a redox protective capacity for Arabidopsis telomerase that may promote survivability in harsh environments.

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“…Tti1 is the largest subunit of the heterotrimeric TTT chaperone complex (Hurov et al, 2010), a specialized chaperone system dedicated to facilitating folding and/or maintenance of the phosphatidylinositol 3-kinase-related kinase (PIKK) proteins (Takai et al, 2007;Takai et al, 2010;Sugimoto, 2018;Elias-Villalobos et al, 2019). PIKKs play important roles in diverse cellular processes in eukaryotes -from response to nutritional stress to regulation of cell growth and transcriptional regulation (Villa et al, 2016;Gonzalez and Hall, 2017;Cheung and Diaz-Santin, 2019;Lustig, 2019). We decided to investigate the relationship between Sis1 and the TTT complex, as we considered PIKKs as plausible essential substrates of the Sis1-Ssa1 Hsp70 chaperone system.…”

Section: Results and Discussion Tti1 Variants Allow Growth Of Cells Having A Deletion Of Sis1mentioning

confidence: 99%

“…PIKKs play important roles in diverse cellular processes in eukaryotes, from response to nutritional stress to regulation of cell growth and transcriptional regulation ( Villa et al. , 2016 ; Gonzalez and Hall, 2017 ; Cheung and Diaz-Santin, 2019 ; Lustig, 2019 ). We decided to investigate the relationship between Sis1 and the TTT complex, as we considered PIKKs as plausible essential substrates of the Sis1–Ssa1 Hsp70 chaperone system.…”

Section: Resultsmentioning

confidence: 99%

Essentiality of Sis1, a J-domain protein Hsp70 cochaperone, can be overcome by Tti1, a specialized PIKK chaperone

Schilke

Craig

2022

MBoC

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J-domain protein cochaperones drive much of the functional diversity of Hsp70-based chaperone systems. Sis1 is the only essential J-domain protein of the cytosol/nucleus of Saccharomyces cerevisiae. Why it is required for cell growth is not understood, nor is how critical its role in regulation of heat shock transcription factor 1 (Hsf1). We report that single residue substitutions in Tti1, a component of the heterotrimeric TTT complex, a specialized chaperone system for phosphatidylinositol 3-kinase-related kinase (PIKK) proteins, allow growth of cells lacking Sis1. Upon depletion of Sis1, cells become hypersensitive to rapamycin, a specific inhibitor of TORC1 kinase. In addition, levels of the three essential PIKKs (Mec1, Tra1, and Tor2), as well as Tor1, decrease upon Sis1depletion. Overexpression of Tti1 allows growth, without an increase in the other subunits of the TTT complex, Tel2 and Tti2, suggesting that it can function independent of the complex. Cells lacking Sis1, with viability supported by Tti1 suppressor, substantially upregulate some, but not all, heat shock elements activated by Hsf1. Together, our results suggest that Sis1 is required as a cochaperone of Hsp70 for the folding/maintenance of PIKKs making Sis1 an essential gene, and its requirement for Hsf1 regulation is more nuanced than generally appreciated.

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Towards the Mechanism of Yeast Telomere Dynamics

Cited by 8 publications

References 54 publications

Role of folding kinetics of secondary structures in telomeric G-overhangs in the regulation of telomere maintenance in Saccharomyces cerevisiae

Role of folding kinetics of secondary structures in telomeric G-overhangs in the regulation of telomere maintenance in Saccharomyces cerevisiae

Arabidopsis telomerase takes off by uncoupling enzyme activity from telomere length maintenance in space

Essentiality of Sis1, a J-domain protein Hsp70 cochaperone, can be overcome by Tti1, a specialized PIKK chaperone

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