Role of the ESCRT Complexes in Telomere Biology

Publikationstyp:
Zeitschriftenaufsatz
Metadaten:
Autoren
  • Anna K Dieckmann
  • Vera Babin
  • Yaniv Harari
  • Roland Eils
  • Rainer Koenig
  • Brian Luke
  • Martin Kupiec
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000392079500021&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1128/mBio.01793-16
Externe Identifier
  • Clarivate Analytics Document Solution ID: EH9GK
  • PubMed Identifier: 27834202
ISSN
2150-7511
Ausgabe der Veröffentlichung
6
Zeitschrift
MBIO
Artikelnummer
ARTN e01793-16
Datum der Veröffentlichung
2016
Status
Published
Titel
Role of the ESCRT Complexes in Telomere Biology
Sub types
  • Article
Ausgabe der Zeitschrift
7

Datenquelle: Web of Science (Lite)

Andere Metadatenquellen:
Abstract
<jats:title>ABSTRACT</jats:title> <jats:p> 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 <jats:named-content content-type="genus-species">Saccharomyces cerevisiae</jats:named-content> identified a set of genes associated with telomere length maintenance ( <jats:italic>TLM</jats:italic> genes). Among the <jats:italic>tlm</jats:italic> mutants with short telomeres, we found a strong enrichment for those affecting vacuolar and endosomal traffic (particularly the <jats:underline>e</jats:underline> ndosomal <jats:underline>s</jats:underline> orting <jats:underline>c</jats:underline> omplex <jats:underline>r</jats:underline> equired for <jats:underline>t</jats:underline> ransport [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. </jats:p> <jats:p> <jats:bold>IMPORTANCE</jats:bold> 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. </jats:p>
Autoren
  • Anna K Dieckmann
  • Vera Babin
  • Yaniv Harari
  • Roland Eils
  • Rainer König
  • Brian Luke
  • Martin Kupiec
DOI
10.1128/mbio.01793-16
Editoren
  • Kirsten Nielsen
eISSN
2150-7511
ISSN
2161-2129
Ausgabe der Veröffentlichung
6
Zeitschrift
mBio
Sprache
en
Datum der Veröffentlichung
2016
Status
Published
Herausgeber
American Society for Microbiology
Herausgeber URL
http://dx.doi.org/10.1128/mbio.01793-16
Datum der Datenerfassung
2022
Titel
Role of the ESCRT Complexes in Telomere Biology
Ausgabe der Zeitschrift
7

Datenquelle: Crossref

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.<h4>Importance</h4>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.
Addresses
  • Division of Theoretical Bioinformatics (B080), German Cancer Research Center (DKFZ), Heidelberg, Germany.
Autoren
  • Anna K Dieckmann
  • Vera Babin
  • Yaniv Harari
  • Roland Eils
  • Rainer König
  • Brian Luke
  • Martin Kupiec
DOI
10.1128/mbio.01793-16
eISSN
2150-7511
Externe Identifier
  • PubMed Identifier: 27834202
  • PubMed Central ID: PMC5101353
Funding acknowledgements
  • Ministry of Science, Technology and Space:
  • Israel Cancer Research Fund:
  • German Federal Ministry of Education and Research:
Open access
true
ISSN
2150-7511
Ausgabe der Veröffentlichung
6
Zeitschrift
mBio
Schlüsselwörter
  • Telomere
  • Humans
  • Saccharomyces cerevisiae
  • Telomerase
  • DNA-Binding Proteins
  • DNA Repair
  • DNA Replication
  • Mutation
  • Genome, Fungal
  • Endosomal Sorting Complexes Required for Transport
  • Telomere Shortening
  • Telomere Homeostasis
Sprache
eng
Medium
Electronic
Online publication date
2016
Open access status
Open Access
Paginierung
e01793 - e01716
Datum der Veröffentlichung
2016
Status
Published
Publisher licence
CC BY
Datum der Datenerfassung
2016
Titel
Role of the ESCRT Complexes in Telomere Biology.
Sub types
  • research-article
  • Journal Article
Ausgabe der Zeitschrift
7

Files

https://mbio.asm.org/content/mbio/7/6/e01793-16.full.pdf https://europepmc.org/articles/PMC5101353?pdf=render

Datenquelle: Europe PubMed Central

Abstract
UNLABELLED: 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.
Autoren
  • Anna K Dieckmann
  • Vera Babin
  • Yaniv Harari
  • Roland Eils
  • Rainer König
  • Brian Luke
  • Martin Kupiec
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/27834202
DOI
10.1128/mBio.01793-16
eISSN
2150-7511
Externe Identifier
  • PubMed Central ID: PMC5101353
Ausgabe der Veröffentlichung
6
Zeitschrift
mBio
Schlüsselwörter
  • DNA Repair
  • DNA Replication
  • DNA-Binding Proteins
  • Endosomal Sorting Complexes Required for Transport
  • Genome, Fungal
  • Humans
  • Mutation
  • Saccharomyces cerevisiae
  • Telomerase
  • Telomere
  • Telomere Homeostasis
  • Telomere Shortening
Sprache
eng
Country
United States
PII
mBio.01793-16
Datum der Veröffentlichung
2016
Status
Published online
Datum, an dem der Datensatz öffentlich gemacht wurde
2017
Titel
Role of the ESCRT Complexes in Telomere Biology.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
7

Datenquelle: PubMed

Abstract
UNLABELLED 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.
Autoren
  • Anna K Dieckmann
  • Vera Babin
  • Yaniv Harari
  • Roland Eils
  • Rainer König
  • Brian Luke
  • Martin Kupiec
DOI
10.1128/mBio.01793-16
Zeitschrift
mBio
Notes
keywords: DNA Repair;DNA Replication;DNA-Binding Proteins/metabolism;Endosomal Sorting Complexes Required for Transport/genetics/metabolism;Genome, Fungal;Humans;Mutation;Saccharomyces cerevisiae/genetics;Telomerase/metabolism;Telomere Homeostasis/genetics/physiology;Telomere Shortening/genetics/physiology;Telomere/genetics/metabolism/physiology
Artikelnummer
6
Datum der Veröffentlichung
2016
Datum der Datenerfassung
2023
Titel
Role of the ESCRT Complexes in Telomere Biology
Sub types
  • article
Ausgabe der Zeitschrift
7

Datenquelle: Manual

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