Role of the ESCRT Complexes in Telomere Biology

ABSTRACT Eukaryotic chromosomal ends are protected by telomeres from fusion, degradation, and unwanted double-strand break repair events. Therefore, telomeres preserve genome stability and integrity. Telomere length can be maintained by telomerase, which is expressed in most human primary tumors but...

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Autores principales:	Anna K. Dieckmann, Vera Babin, Yaniv Harari, Roland Eils, Rainer König, Brian Luke, Martin Kupiec
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/236579e0e3bb49fda28f7fded64ac247
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spelling	oai:doaj.org-article:236579e0e3bb49fda28f7fded64ac2472021-11-15T15:50:15ZRole of the ESCRT Complexes in Telomere Biology10.1128/mBio.01793-162150-7511https://doaj.org/article/236579e0e3bb49fda28f7fded64ac2472016-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01793-16https://doaj.org/toc/2150-7511ABSTRACT Eukaryotic chromosomal ends are protected by telomeres from fusion, degradation, and unwanted double-strand break repair events. Therefore, telomeres preserve genome stability and integrity. Telomere length can be maintained by telomerase, which is expressed in most human primary tumors but is not expressed in the majority of somatic cells. Thus, telomerase may be a highly relevant anticancer drug target. Genome-wide studies in the yeast Saccharomyces cerevisiae identified a set of genes associated with telomere length maintenance (TLM genes). Among the tlm mutants with short telomeres, we found a strong enrichment for those affecting vacuolar and endosomal traffic (particularly the endosomal sorting complex required for transport [ESCRT] pathway). Here, we present our results from investigating the surprising link between telomere shortening and the ESCRT machinery. Our data show that the whole ESCRT system is required to safeguard proper telomere length maintenance. We propose a model of impaired end resection resulting in too little telomeric overhang, such that Cdc13 binding is prevented, precluding either telomerase recruitment or telomeric overhang protection. IMPORTANCE Telomeres are the ends of eukaryotic chromosomes. They are necessary for the proper replication of the genome and protect the chromosomes from degradation. In a large-scale systematic screen for mutants that affect telomere length in yeast, we found that mutations in any of the genes encoding the ESCRT complexes, required for the formation of transport vesicles within the cell, cause telomere shortening. We carried out an analysis of the mechanisms disrupted in these mutants and found that they are defective for the ability to elongate short telomeres, probably due to faulty end processing. We discuss the significance of these findings and how they could be relevant to anticancer therapies.Anna K. DieckmannVera BabinYaniv HarariRoland EilsRainer KönigBrian LukeMartin KupiecAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 7, Iss 6 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Anna K. Dieckmann Vera Babin Yaniv Harari Roland Eils Rainer König Brian Luke Martin Kupiec Role of the ESCRT Complexes in Telomere Biology
description	ABSTRACT Eukaryotic chromosomal ends are protected by telomeres from fusion, degradation, and unwanted double-strand break repair events. Therefore, telomeres preserve genome stability and integrity. Telomere length can be maintained by telomerase, which is expressed in most human primary tumors but is not expressed in the majority of somatic cells. Thus, telomerase may be a highly relevant anticancer drug target. Genome-wide studies in the yeast Saccharomyces cerevisiae identified a set of genes associated with telomere length maintenance (TLM genes). Among the tlm mutants with short telomeres, we found a strong enrichment for those affecting vacuolar and endosomal traffic (particularly the endosomal sorting complex required for transport [ESCRT] pathway). Here, we present our results from investigating the surprising link between telomere shortening and the ESCRT machinery. Our data show that the whole ESCRT system is required to safeguard proper telomere length maintenance. We propose a model of impaired end resection resulting in too little telomeric overhang, such that Cdc13 binding is prevented, precluding either telomerase recruitment or telomeric overhang protection. IMPORTANCE Telomeres are the ends of eukaryotic chromosomes. They are necessary for the proper replication of the genome and protect the chromosomes from degradation. In a large-scale systematic screen for mutants that affect telomere length in yeast, we found that mutations in any of the genes encoding the ESCRT complexes, required for the formation of transport vesicles within the cell, cause telomere shortening. We carried out an analysis of the mechanisms disrupted in these mutants and found that they are defective for the ability to elongate short telomeres, probably due to faulty end processing. We discuss the significance of these findings and how they could be relevant to anticancer therapies.
format	article
author	Anna K. Dieckmann Vera Babin Yaniv Harari Roland Eils Rainer König Brian Luke Martin Kupiec
author_facet	Anna K. Dieckmann Vera Babin Yaniv Harari Roland Eils Rainer König Brian Luke Martin Kupiec
author_sort	Anna K. Dieckmann
title	Role of the ESCRT Complexes in Telomere Biology
title_short	Role of the ESCRT Complexes in Telomere Biology
title_full	Role of the ESCRT Complexes in Telomere Biology
title_fullStr	Role of the ESCRT Complexes in Telomere Biology
title_full_unstemmed	Role of the ESCRT Complexes in Telomere Biology
title_sort	role of the escrt complexes in telomere biology
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/236579e0e3bb49fda28f7fded64ac247
work_keys_str_mv	AT annakdieckmann roleoftheescrtcomplexesintelomerebiology AT verababin roleoftheescrtcomplexesintelomerebiology AT yanivharari roleoftheescrtcomplexesintelomerebiology AT rolandeils roleoftheescrtcomplexesintelomerebiology AT rainerkonig roleoftheescrtcomplexesintelomerebiology AT brianluke roleoftheescrtcomplexesintelomerebiology AT martinkupiec roleoftheescrtcomplexesintelomerebiology
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Role of the ESCRT Complexes in Telomere Biology

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