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Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader

Telomeres cap and protect the linear eukaryotic chromosomes. Telomere length is determined by an equilibrium between positive and negative regulators of telomerase activity. A systematic screen for yeast mutants that affect telomere length maintenance in the yeast Saccharomyces cerevisiae revealed t...

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Autores principales: Singh, Pragyan, Gazy, Inbal, Kupiec, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396338/
https://www.ncbi.nlm.nih.gov/pubmed/37530521
http://dx.doi.org/10.7554/eLife.86990
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author Singh, Pragyan
Gazy, Inbal
Kupiec, Martin
author_facet Singh, Pragyan
Gazy, Inbal
Kupiec, Martin
author_sort Singh, Pragyan
collection PubMed
description Telomeres cap and protect the linear eukaryotic chromosomes. Telomere length is determined by an equilibrium between positive and negative regulators of telomerase activity. A systematic screen for yeast mutants that affect telomere length maintenance in the yeast Saccharomyces cerevisiae revealed that mutations in any of ~500 genes affects telomere length. One of the genes that, when mutated, causes telomere elongation is ELG1, which encodes an unloader of PCNA, the processivity factor for replicative DNA polymerases. PCNA can undergo SUMOylation on two conserved residues, K164 and K127, or ubiquitination at lysine 164. These modifications have already been implicated in genome stability processes. We report that SUMOylated PCNA acts as a signal that positively regulates telomerase activity. We also uncovered physical interactions between Elg1 and the CST (Cdc13-Stn1-Ten) complex and addressed the mechanism by which Elg1 and Stn1 negatively regulates telomere elongation, coordinated by SUMO. We discuss these results with respect to how chromosomal replication and telomere elongation are coordinated.
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spelling pubmed-103963382023-08-03 Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader Singh, Pragyan Gazy, Inbal Kupiec, Martin eLife Chromosomes and Gene Expression Telomeres cap and protect the linear eukaryotic chromosomes. Telomere length is determined by an equilibrium between positive and negative regulators of telomerase activity. A systematic screen for yeast mutants that affect telomere length maintenance in the yeast Saccharomyces cerevisiae revealed that mutations in any of ~500 genes affects telomere length. One of the genes that, when mutated, causes telomere elongation is ELG1, which encodes an unloader of PCNA, the processivity factor for replicative DNA polymerases. PCNA can undergo SUMOylation on two conserved residues, K164 and K127, or ubiquitination at lysine 164. These modifications have already been implicated in genome stability processes. We report that SUMOylated PCNA acts as a signal that positively regulates telomerase activity. We also uncovered physical interactions between Elg1 and the CST (Cdc13-Stn1-Ten) complex and addressed the mechanism by which Elg1 and Stn1 negatively regulates telomere elongation, coordinated by SUMO. We discuss these results with respect to how chromosomal replication and telomere elongation are coordinated. eLife Sciences Publications, Ltd 2023-08-02 /pmc/articles/PMC10396338/ /pubmed/37530521 http://dx.doi.org/10.7554/eLife.86990 Text en © 2023, Singh et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Chromosomes and Gene Expression
Singh, Pragyan
Gazy, Inbal
Kupiec, Martin
Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader
title Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader
title_full Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader
title_fullStr Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader
title_full_unstemmed Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader
title_short Control of telomere length in yeast by SUMOylated PCNA and the Elg1 PCNA unloader
title_sort control of telomere length in yeast by sumoylated pcna and the elg1 pcna unloader
topic Chromosomes and Gene Expression
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10396338/
https://www.ncbi.nlm.nih.gov/pubmed/37530521
http://dx.doi.org/10.7554/eLife.86990
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