Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes

El pdf del artículo es el manuscrito de autor.-- et al.

Detalles Bibliográficos
Autores: Bermejo, Rodrigo, Liberi, Giordano
Tipo de recurso: artículo
Fecha de publicación:2012
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/67486
Acceso en línea:http://hdl.handle.net/10261/67486
Access Level:acceso abierto
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spelling Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genesBermejo, RodrigoLiberi, GiordanoEl pdf del artículo es el manuscrito de autor.-- et al.Transcription hinders replication fork progression and stability. The ATR checkpoint and specialized DNA helicases assist DNA synthesis across transcription units to protect genome integrity. Combining genomic and genetic approaches together with the analysis of replication intermediates, we searched for factors coordinating replication with transcription. We show that the Sen1/Senataxin DNA/RNA helicase associates with forks, promoting their progression across RNA polymerase II (RNAPII)-transcribed genes. sen1 mutants accumulate aberrant DNA structures and DNA-RNA hybrids while forks clash head-on with RNAPII transcription units. These replication defects correlate with hyperrecombination and checkpoint activation in sen1 mutants. The Sen1 function at the forks is separable from its role in RNA processing. Our data, besides unmasking a key role for Senataxin in coordinating replication with transcription, provide a framework for understanding the pathological mechanisms caused by Senataxin deficiencies and leading to the severe neurodegenerative diseases ataxia with oculomotor apraxia type 2 and amyotrophic lateral sclerosis 4. © 2012 Elsevier Inc.R.B. is supported by the Spanish Ministry of Science and Innovation (RYC-2010-07131 and BFU2011-24909) and the European Community’s FP7 (under grant agreement 293770). This work was supported by grants from Associazione Italiana per la Ricerca sul Cancro (AIRC) and Telethon-Italy (GGP08057) to G.L.Peer ReviewedElsevier2013201320122013info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501http://hdl.handle.net/10261/67486reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/EC/FP7/293770http://dx.doi.org/10.1016/j.cell.2012.09.041info:eu-repo/semantics/openAccessoai:digital.csic.es:10261/674862026-05-22T06:33:51Z
dc.title.none.fl_str_mv Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
title Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
spellingShingle Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
Bermejo, Rodrigo
title_short Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
title_full Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
title_fullStr Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
title_full_unstemmed Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
title_sort Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes
dc.creator.none.fl_str_mv Bermejo, Rodrigo
Liberi, Giordano
author Bermejo, Rodrigo
author_facet Bermejo, Rodrigo
Liberi, Giordano
author_role author
author2 Liberi, Giordano
author2_role author
description El pdf del artículo es el manuscrito de autor.-- et al.
publishDate 2012
dc.date.none.fl_str_mv 2012
2013
2013
2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
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dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/67486
url http://hdl.handle.net/10261/67486
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/EC/FP7/293770
http://dx.doi.org/10.1016/j.cell.2012.09.041
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
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