The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage

Autoren

Juan Lafuente-Barquero
Sarah Luke-Glaser
Marco Graf
Sonia Silva
Belén Gómez-González
Arianna Lockhart
Michael Lisby
Andrés Aguilera
Brian Luke

DOI

10.1371/journal.pgen.1007136

Editoren

Francesca Storici

eISSN

1553-7404

Ausgabe der Veröffentlichung

12

Zeitschrift

PLOS Genetics

Sprache

en

Online publication date

2017

Paginierung

e1007136 - e1007136

Status

Published online

Herausgeber

Public Library of Science (PLoS)

Herausgeber URL

http://dx.doi.org/10.1371/journal.pgen.1007136

Datum der Datenerfassung

2022

Titel

The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage

Ausgabe der Zeitschrift

13

Datenquelle: Crossref

Abstract

RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci. Mph1 forms foci when RNA-DNA hybrids accumulate, e.g. in RNase H or THO-complex mutants and at short telomeres. Mph1, however is a double-edged sword, whose action at hybrids must be regulated by the Smc5/6 complex. This is underlined by the observation that simultaneous inactivation of RNase H2 and Smc5/6 results in Mph1-dependent synthetic lethality, which is likely due to an accumulation of toxic recombination intermediates. The data presented here support a model, where Mph1's helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids.

Addresses

Andalusian Center for Molecular Biology and Regenerative Medicine-CABIMER, Universidad de Sevilla-CSIC-Universidad Pablo de Olavide, Avda. Americo Vespucio 24, Seville, Spain.

Autoren

Juan Lafuente-Barquero
Sarah Luke-Glaser
Marco Graf
Sonia Silva
Belén Gómez-González
Arianna Lockhart
Michael Lisby
Andrés Aguilera
Brian Luke

DOI

10.1371/journal.pgen.1007136

eISSN

1553-7404

Externe Identifier

PubMed Identifier: 29281624
PubMed Central ID: PMC5760084

Funding acknowledgements

Villum Fonden: 00011407
European Research Council: 242905

Open access

true

ISSN

1553-7390

Ausgabe der Veröffentlichung

12

Zeitschrift

PLoS genetics

Schlüsselwörter

Saccharomyces cerevisiae
DNA Damage
RNA Helicases
Cell Cycle Proteins
Saccharomyces cerevisiae Proteins
DNA
RNA, Fungal
DNA Repair
DNA Replication
DEAD-box RNA Helicases
Ribonuclease H

Sprache

eng

Medium

Electronic-eCollection

Online publication date

2017

Open access status

Open Access

Paginierung

e1007136

Datum der Veröffentlichung

2017

Status

Published

Publisher licence

CC BY

Datum der Datenerfassung

2017

Titel

The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage.

Sub types

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

Ausgabe der Zeitschrift

13

Files

https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1007136&type=printable https://europepmc.org/articles/PMC5760084?pdf=render

Datenquelle: Europe PubMed Central

Abstract

RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci. Mph1 forms foci when RNA-DNA hybrids accumulate, e.g. in RNase H or THO-complex mutants and at short telomeres. Mph1, however is a double-edged sword, whose action at hybrids must be regulated by the Smc5/6 complex. This is underlined by the observation that simultaneous inactivation of RNase H2 and Smc5/6 results in Mph1-dependent synthetic lethality, which is likely due to an accumulation of toxic recombination intermediates. The data presented here support a model, where Mph1's helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids.

Date of acceptance

2017

Autoren

Juan Lafuente-Barquero
Sarah Luke-Glaser
Marco Graf
Sonia Silva
Belén Gómez-González
Arianna Lockhart
Michael Lisby
Andrés Aguilera
Brian Luke

Autoren-URL

https://www.ncbi.nlm.nih.gov/pubmed/29281624

DOI

10.1371/journal.pgen.1007136

eISSN

1553-7404

Externe Identifier

PubMed Central ID: PMC5760084

Ausgabe der Veröffentlichung

12

Zeitschrift

PLoS Genet

Schlüsselwörter

Cell Cycle Proteins
DEAD-box RNA Helicases
DNA
DNA Damage
DNA Repair
DNA Replication
RNA Helicases
RNA, Fungal
Ribonuclease H
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins

Sprache

eng

Country

United States

Paginierung

e1007136

PII

PGENETICS-D-17-00679

Datum der Veröffentlichung

2017

Status

Published online

Datum, an dem der Datensatz öffentlich gemacht wurde

2018

Titel

The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage.

Sub types

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

Ausgabe der Zeitschrift

13

Datenquelle: PubMed

Abstract

RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In the absence of RNase H enzymes, RNA-DNA hybrids accumulate, resulting in replication stress, DNA damage and compromised genomic integrity. We demonstrate that Mph1, the yeast homolog of Fanconi anemia protein M (FANCM), is required for cell viability in the absence of RNase H enzymes. The integrity of the Mph1 helicase domain is crucial to prevent the accumulation of RNA-DNA hybrids and RNA-DNA hybrid-dependent DNA damage, as determined by Rad52 foci. Mph1 forms foci when RNA-DNA hybrids accumulate, e.g. in RNase H or THO-complex mutants and at short telomeres. Mph1, however is a double-edged sword, whose action at hybrids must be regulated by the Smc5/6 complex. This is underlined by the observation that simultaneous inactivation of RNase H2 and Smc5/6 results in Mph1-dependent synthetic lethality, which is likely due to an accumulation of toxic recombination intermediates. The data presented here support a model, where Mph1’s helicase activity plays a crucial role in responding to persistent RNA-DNA hybrids.

Autoren

Juan Lafuente-Barquero
Sarah Luke-Glaser
Marco Graf
Sonia Silva
Belén Gómez-González
Arianna Lockhart
Michael Lisby
Andrés Aguilera
Brian Luke

DOI

10.1371/journal.pgen.1007136

Zeitschrift

PLoS genetics

Notes

keywords: Cell Cycle Proteins/genetics/metabolism;DEAD-box RNA Helicases/genetics/metabolism;DNA Damage;DNA Repair;DNA Replication/genetics/physiology;DNA/metabolism;Ribonuclease H/genetics;RNA Helicases/metabolism;RNA, Fungal/genetics/metabolism;Saccharomyces cerevisiae Proteins/genetics/metabolism;Saccharomyces cerevisiae/genetics

Artikelnummer

12

Paginierung

e1007136 - e1007136

Datum der Veröffentlichung

2017

Datum der Datenerfassung

2023

Titel

The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage

Sub types

article

Ausgabe der Zeitschrift

13

Datenquelle: Manual

The Smc5/6 complex regulates the yeast Mph1 helicase at RNA-DNA hybrid-mediated DNA damage

Files

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