Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse

During S phase, replication forks can encounter several obstacles that lead to fork stalling, which if persistent might result in fork collapse. To avoid this collapse and to preserve the competence to restart, cells have developed mechanisms that maintain fork stability upon replication stress. In...

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Detalles Bibliográficos
Autores: Ercilla Eguiarte, Amaia, Feu i Coll, Sònia, Aranda, Sergi, Llopis, Alba, Brynjólfsdóttir, S.H., Sørensen, Claus Storgaard, Toledo, Luis I., Agell i Jané, Neus
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2019
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/137967
Acceso en línea:https://hdl.handle.net/2445/137967
Access Level:acceso abierto
Palabra clave:Duplicació de l'ADN
Biologia molecular
ADN
DNA replication
Molecular biology
DNA
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spelling Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapseErcilla Eguiarte, AmaiaFeu i Coll, SòniaAranda, SergiLlopis, AlbaBrynjólfsdóttir, S.H.Sørensen, Claus StorgaardToledo, Luis I.Agell i Jané, NeusDuplicació de l'ADNBiologia molecularADNDNA replicationMolecular biologyDNADuring S phase, replication forks can encounter several obstacles that lead to fork stalling, which if persistent might result in fork collapse. To avoid this collapse and to preserve the competence to restart, cells have developed mechanisms that maintain fork stability upon replication stress. In this study, we aimed to understand the mechanisms involved in fork stability maintenance in non-transformed human cells by performing an isolation of proteins on nascent DNA-mass spectrometry analysis in hTERT-RPE cells under different replication stress conditions. Our results show that acute hydroxyurea-induced replication blockade causes the accumulation of large amounts of single-stranded DNA at the fork. Remarkably, this results in the disengagement of replisome components from nascent DNA without compromising fork restart. Notably, Cdc45-MCM-GINS helicase maintains its integrity and replisome components remain associated with chromatin upon acute hydroxyurea treatment, whereas replisome stability is lost upon a sustained replication stress that compromises the competence to restart.Springer Verlag2019info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/137967Articles publicats en revistes (Biomedicina)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1007/s00018-019-03206-1Cellular and Molecular Life Sciences, 2019https://doi.org/10.1007/s00018-019-03206-1(c) Birkhäuser Basel, 2019info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1379672026-05-27T06:46:51Z
dc.title.none.fl_str_mv Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
title Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
spellingShingle Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
Ercilla Eguiarte, Amaia
Duplicació de l'ADN
Biologia molecular
ADN
DNA replication
Molecular biology
DNA
title_short Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
title_full Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
title_fullStr Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
title_full_unstemmed Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
title_sort Acute hydroxyurea-induced replication blockade results in replisome components disengagement from nascent DNA without causing fork collapse
dc.creator.none.fl_str_mv Ercilla Eguiarte, Amaia
Feu i Coll, Sònia
Aranda, Sergi
Llopis, Alba
Brynjólfsdóttir, S.H.
Sørensen, Claus Storgaard
Toledo, Luis I.
Agell i Jané, Neus
author Ercilla Eguiarte, Amaia
author_facet Ercilla Eguiarte, Amaia
Feu i Coll, Sònia
Aranda, Sergi
Llopis, Alba
Brynjólfsdóttir, S.H.
Sørensen, Claus Storgaard
Toledo, Luis I.
Agell i Jané, Neus
author_role author
author2 Feu i Coll, Sònia
Aranda, Sergi
Llopis, Alba
Brynjólfsdóttir, S.H.
Sørensen, Claus Storgaard
Toledo, Luis I.
Agell i Jané, Neus
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Duplicació de l'ADN
Biologia molecular
ADN
DNA replication
Molecular biology
DNA
topic Duplicació de l'ADN
Biologia molecular
ADN
DNA replication
Molecular biology
DNA
description During S phase, replication forks can encounter several obstacles that lead to fork stalling, which if persistent might result in fork collapse. To avoid this collapse and to preserve the competence to restart, cells have developed mechanisms that maintain fork stability upon replication stress. In this study, we aimed to understand the mechanisms involved in fork stability maintenance in non-transformed human cells by performing an isolation of proteins on nascent DNA-mass spectrometry analysis in hTERT-RPE cells under different replication stress conditions. Our results show that acute hydroxyurea-induced replication blockade causes the accumulation of large amounts of single-stranded DNA at the fork. Remarkably, this results in the disengagement of replisome components from nascent DNA without compromising fork restart. Notably, Cdc45-MCM-GINS helicase maintains its integrity and replisome components remain associated with chromatin upon acute hydroxyurea treatment, whereas replisome stability is lost upon a sustained replication stress that compromises the competence to restart.
publishDate 2019
dc.date.none.fl_str_mv 2019
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/137967
url https://hdl.handle.net/2445/137967
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/s00018-019-03206-1
Cellular and Molecular Life Sciences, 2019
https://doi.org/10.1007/s00018-019-03206-1
dc.rights.none.fl_str_mv (c) Birkhäuser Basel, 2019
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Birkhäuser Basel, 2019
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Springer Verlag
publisher.none.fl_str_mv Springer Verlag
dc.source.none.fl_str_mv Articles publicats en revistes (Biomedicina)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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