The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast

Autoren

Sarah Luke-Glaser
Brian Luke

DOI

10.1371/journal.pone.0042028

Editoren

Arthur J Lustig

eISSN

1932-6203

Ausgabe der Veröffentlichung

7

Zeitschrift

PLoS ONE

Sprache

en

Online publication date

2012

Paginierung

e42028 - e42028

Status

Published online

Herausgeber

Public Library of Science (PLoS)

Herausgeber URL

http://dx.doi.org/10.1371/journal.pone.0042028

Datum der Datenerfassung

2022

Titel

The Mph1 Helicase Can Promote Telomere Uncapping and Premature Senescence in Budding Yeast

Ausgabe der Zeitschrift

7

Datenquelle: Crossref

Abstract

Double strand breaks (DSBs) can be repaired via either Non-Homologous End Joining (NHEJ) or Homology directed Repair (HR). Telomeres, which resemble DSBs, are refractory to repair events in order to prevent chromosome end fusions and genomic instability. In some rare instances telomeres engage in Break-Induced Replication (BIR), a type of HR, in order to maintain telomere length in the absence of the enzyme telomerase. Here we have investigated how the yeast helicase, Mph1, affects DNA repair at both DSBs and telomeres. We have found that overexpressed Mph1 strongly inhibits BIR at internal DSBs however allows it to proceed at telomeres. Furthermore, while overexpressed Mph1 potently inhibits NHEJ at telomeres it has no effect on NHEJ at DSBs within the chromosome. At telomeres Mph1 is able to promote telomere uncapping and the accumulation of ssDNA, which results in premature senescence in the absence of telomerase. We propose that Mph1 is able to direct repair towards HR (thereby inhibiting NHEJ) at telomeres by remodeling them into a nuclease-sensitive structure, which promotes the accumulation of a recombinogenic ssDNA intermediate. We thus put forward that Mph1 is a double-edge sword at the telomere, it prevents NHEJ, but promotes senescence in cells with dysfunctional telomeres by increasing the levels of ssDNA.

Addresses

Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), DKFZ-ZMBH Allianz, Heidelberg, Germany. s.luke-glaser@zmbh.uni-heidelberg.de

Autoren

Sarah Luke-Glaser
Brian Luke

DOI

10.1371/journal.pone.0042028

eISSN

1932-6203

Externe Identifier

PubMed Identifier: 22848695
PubMed Central ID: PMC3407055

Open access

true

ISSN

1932-6203

Ausgabe der Veröffentlichung

7

Zeitschrift

PloS one

Schlüsselwörter

Telomere
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
DNA, Fungal
DNA, Single-Stranded
DNA Replication
Gene Expression Regulation, Fungal
Mutation
DEAD-box RNA Helicases
DNA Breaks, Double-Stranded
DNA End-Joining Repair

Sprache

eng

Medium

Print-Electronic

Online publication date

2012

Open access status

Open Access

Paginierung

e42028

Datum der Veröffentlichung

2012

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2012

Titel

The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.

Sub types

Research Support, Non-U.S. Gov't
research-article
Journal Article

Ausgabe der Zeitschrift

7

Files

https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0042028&type=printable https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22848695/pdf/?tool=EBI https://europepmc.org/articles/PMC3407055?pdf=render

Datenquelle: Europe PubMed Central

Abstract

Double strand breaks (DSBs) can be repaired via either Non-Homologous End Joining (NHEJ) or Homology directed Repair (HR). Telomeres, which resemble DSBs, are refractory to repair events in order to prevent chromosome end fusions and genomic instability. In some rare instances telomeres engage in Break-Induced Replication (BIR), a type of HR, in order to maintain telomere length in the absence of the enzyme telomerase. Here we have investigated how the yeast helicase, Mph1, affects DNA repair at both DSBs and telomeres. We have found that overexpressed Mph1 strongly inhibits BIR at internal DSBs however allows it to proceed at telomeres. Furthermore, while overexpressed Mph1 potently inhibits NHEJ at telomeres it has no effect on NHEJ at DSBs within the chromosome. At telomeres Mph1 is able to promote telomere uncapping and the accumulation of ssDNA, which results in premature senescence in the absence of telomerase. We propose that Mph1 is able to direct repair towards HR (thereby inhibiting NHEJ) at telomeres by remodeling them into a nuclease-sensitive structure, which promotes the accumulation of a recombinogenic ssDNA intermediate. We thus put forward that Mph1 is a double-edge sword at the telomere, it prevents NHEJ, but promotes senescence in cells with dysfunctional telomeres by increasing the levels of ssDNA.

Date of acceptance

2012

Autoren

Sarah Luke-Glaser
Brian Luke

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/22848695

DOI

10.1371/journal.pone.0042028

eISSN

1932-6203

Externe Identifier

PubMed Central ID: PMC3407055

Ausgabe der Veröffentlichung

7

Zeitschrift

PLoS One

Schlüsselwörter

DEAD-box RNA Helicases
DNA Breaks, Double-Stranded
DNA End-Joining Repair
DNA Replication
DNA, Fungal
DNA, Single-Stranded
Gene Expression Regulation, Fungal
Mutation
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins
Telomere

Sprache

eng

Country

United States

Paginierung

e42028

PII

PONE-D-12-11344

Datum der Veröffentlichung

2012

Status

Published

Datum, an dem der Datensatz öffentlich gemacht wurde

2013

Titel

The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast.

Sub types

Journal Article
Research Support, Non-U.S. Gov't

Ausgabe der Zeitschrift

7

Datenquelle: PubMed

Abstract

Double strand breaks (DSBs) can be repaired via either Non-Homologous End Joining (NHEJ) or Homology directed Repair (HR). Telomeres, which resemble DSBs, are refractory to repair events in order to prevent chromosome end fusions and genomic instability. In some rare instances telomeres engage in Break-Induced Replication (BIR), a type of HR, in order to maintain telomere length in the absence of the enzyme telomerase. Here we have investigated how the yeast helicase, Mph1, affects DNA repair at both DSBs and telomeres. We have found that overexpressed Mph1 strongly inhibits BIR at internal DSBs however allows it to proceed at telomeres. Furthermore, while overexpressed Mph1 potently inhibits NHEJ at telomeres it has no effect on NHEJ at DSBs within the chromosome. At telomeres Mph1 is able to promote telomere uncapping and the accumulation of ssDNA, which results in premature senescence in the absence of telomerase. We propose that Mph1 is able to direct repair towards HR (thereby inhibiting NHEJ) at telomeres by remodeling them into a nuclease-sensitive structure, which promotes the accumulation of a recombinogenic ssDNA intermediate. We thus put forward that Mph1 is a double-edge sword at the telomere, it prevents NHEJ, but promotes senescence in cells with dysfunctional telomeres by increasing the levels of ssDNA.

Autoren

Sarah Luke-Glaser
Brian Luke

DOI

10.1371/journal.pone.0042028

Zeitschrift

PloS one

Notes

keywords: DEAD-box RNA Helicases/genetics/metabolism;DNA Breaks, Double-Stranded;DNA End-Joining Repair/genetics;DNA Replication/genetics;DNA, Fungal/biosynthesis/genetics;DNA, Single-Stranded/biosynthesis/genetics;Gene Expression Regulation, Fungal;Mutation;Saccharomyces cerevisiae Proteins/genetics/metabolism;Saccharomyces cerevisiae/cytology/enzymology/genetics;Telomere/genetics

Artikelnummer

7

Paginierung

e42028 - e42028

Datum der Veröffentlichung

2012

Datum der Datenerfassung

2023

Titel

The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast

Sub types

article

Ausgabe der Zeitschrift

7

Datenquelle: Manual

The Mph1 helicase can promote telomere uncapping and premature senescence in budding yeast

Files

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