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Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse

The completion of genome duplication during the cell cycle is threatened by the presence of replication fork barriers (RFBs). Following collision with a RFB, replication proteins can dissociate from the stalled fork (fork collapse) rendering it incapable of further DNA synthesis unless recombination...

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Autores principales: Nguyen, Michael O, Jalan, Manisha, Morrow, Carl A, Osman, Fekret, Whitby, Matthew C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407270/
https://www.ncbi.nlm.nih.gov/pubmed/25806683
http://dx.doi.org/10.7554/eLife.04539
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author Nguyen, Michael O
Jalan, Manisha
Morrow, Carl A
Osman, Fekret
Whitby, Matthew C
author_facet Nguyen, Michael O
Jalan, Manisha
Morrow, Carl A
Osman, Fekret
Whitby, Matthew C
author_sort Nguyen, Michael O
collection PubMed
description The completion of genome duplication during the cell cycle is threatened by the presence of replication fork barriers (RFBs). Following collision with a RFB, replication proteins can dissociate from the stalled fork (fork collapse) rendering it incapable of further DNA synthesis unless recombination intervenes to restart replication. We use time-lapse microscopy and genetic assays to show that recombination is initiated within ∼10 min of replication fork blockage at a site-specific barrier in fission yeast, leading to a restarted fork within ∼60 min, which is only prevented/curtailed by the arrival of the opposing replication fork. The restarted fork is susceptible to further collapse causing hyper-recombination downstream of the barrier. Surprisingly, in our system fork restart is unnecessary for maintaining cell viability. Seemingly, the risk of failing to complete replication prior to mitosis is sufficient to warrant the induction of recombination even though it can cause deleterious genetic change. DOI: http://dx.doi.org/10.7554/eLife.04539.001
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spelling pubmed-44072702015-04-24 Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse Nguyen, Michael O Jalan, Manisha Morrow, Carl A Osman, Fekret Whitby, Matthew C eLife Genes and Chromosomes The completion of genome duplication during the cell cycle is threatened by the presence of replication fork barriers (RFBs). Following collision with a RFB, replication proteins can dissociate from the stalled fork (fork collapse) rendering it incapable of further DNA synthesis unless recombination intervenes to restart replication. We use time-lapse microscopy and genetic assays to show that recombination is initiated within ∼10 min of replication fork blockage at a site-specific barrier in fission yeast, leading to a restarted fork within ∼60 min, which is only prevented/curtailed by the arrival of the opposing replication fork. The restarted fork is susceptible to further collapse causing hyper-recombination downstream of the barrier. Surprisingly, in our system fork restart is unnecessary for maintaining cell viability. Seemingly, the risk of failing to complete replication prior to mitosis is sufficient to warrant the induction of recombination even though it can cause deleterious genetic change. DOI: http://dx.doi.org/10.7554/eLife.04539.001 eLife Sciences Publications, Ltd 2015-03-25 /pmc/articles/PMC4407270/ /pubmed/25806683 http://dx.doi.org/10.7554/eLife.04539 Text en © 2015, Nguyen et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Genes and Chromosomes
Nguyen, Michael O
Jalan, Manisha
Morrow, Carl A
Osman, Fekret
Whitby, Matthew C
Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse
title Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse
title_full Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse
title_fullStr Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse
title_full_unstemmed Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse
title_short Recombination occurs within minutes of replication blockage by RTS1 producing restarted forks that are prone to collapse
title_sort recombination occurs within minutes of replication blockage by rts1 producing restarted forks that are prone to collapse
topic Genes and Chromosomes
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407270/
https://www.ncbi.nlm.nih.gov/pubmed/25806683
http://dx.doi.org/10.7554/eLife.04539
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