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Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription

The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, in sen1 mutants, when a replication fork clashes head-on with transcription is arrested and, as a consequence, the progression...

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Autores principales: Brambati, Alessandra, Zardoni, Luca, Achar, Yathish Jagadheesh, Piccini, Daniele, Galanti, Lorenzo, Colosio, Arianna, Foiani, Marco, Liberi, Giordano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815123/
https://www.ncbi.nlm.nih.gov/pubmed/29059325
http://dx.doi.org/10.1093/nar/gkx945
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author Brambati, Alessandra
Zardoni, Luca
Achar, Yathish Jagadheesh
Piccini, Daniele
Galanti, Lorenzo
Colosio, Arianna
Foiani, Marco
Liberi, Giordano
author_facet Brambati, Alessandra
Zardoni, Luca
Achar, Yathish Jagadheesh
Piccini, Daniele
Galanti, Lorenzo
Colosio, Arianna
Foiani, Marco
Liberi, Giordano
author_sort Brambati, Alessandra
collection PubMed
description The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, in sen1 mutants, when a replication fork clashes head-on with transcription is arrested and, as a consequence, the progression of the sister fork moving in the opposite direction within the same replicon is also impaired. Therefore, sister forks remain coupled when one of the two forks is arrested by transcription, a fate different from that experienced by forks encountering Double Strand Breaks. We also show that dormant origins of replication are activated to ensure DNA synthesis in the proximity to the forks arrested by transcription. Dormant origin firing is not inhibited by the replication checkpoint, rather dormant origins are fired if they cannot be timely inactivated by passive replication. In sen1 mutants, the Mre11 and Mrc1–Ctf4 complexes protect the forks arrested by transcription from processing mediated by the Exo1 nuclease. Thus, a harmless head-on replication-transcription clash resolution requires the fine-tuning of origin firing and coordination among Sen1, Exo1, Mre11 and Mrc1–Ctf4 complexes.
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spelling pubmed-58151232018-02-23 Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription Brambati, Alessandra Zardoni, Luca Achar, Yathish Jagadheesh Piccini, Daniele Galanti, Lorenzo Colosio, Arianna Foiani, Marco Liberi, Giordano Nucleic Acids Res Genome Integrity, Repair and Replication The yeast RNA/DNA helicase Sen1, Senataxin in human, preserves the integrity of replication forks encountering transcription by removing RNA-DNA hybrids. Here we show that, in sen1 mutants, when a replication fork clashes head-on with transcription is arrested and, as a consequence, the progression of the sister fork moving in the opposite direction within the same replicon is also impaired. Therefore, sister forks remain coupled when one of the two forks is arrested by transcription, a fate different from that experienced by forks encountering Double Strand Breaks. We also show that dormant origins of replication are activated to ensure DNA synthesis in the proximity to the forks arrested by transcription. Dormant origin firing is not inhibited by the replication checkpoint, rather dormant origins are fired if they cannot be timely inactivated by passive replication. In sen1 mutants, the Mre11 and Mrc1–Ctf4 complexes protect the forks arrested by transcription from processing mediated by the Exo1 nuclease. Thus, a harmless head-on replication-transcription clash resolution requires the fine-tuning of origin firing and coordination among Sen1, Exo1, Mre11 and Mrc1–Ctf4 complexes. Oxford University Press 2018-02-16 2017-10-20 /pmc/articles/PMC5815123/ /pubmed/29059325 http://dx.doi.org/10.1093/nar/gkx945 Text en © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Genome Integrity, Repair and Replication
Brambati, Alessandra
Zardoni, Luca
Achar, Yathish Jagadheesh
Piccini, Daniele
Galanti, Lorenzo
Colosio, Arianna
Foiani, Marco
Liberi, Giordano
Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
title Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
title_full Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
title_fullStr Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
title_full_unstemmed Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
title_short Dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
title_sort dormant origins and fork protection mechanisms rescue sister forks arrested by transcription
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815123/
https://www.ncbi.nlm.nih.gov/pubmed/29059325
http://dx.doi.org/10.1093/nar/gkx945
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