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Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1

Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts par...

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Autores principales: Ölmezer, Gizem, Levikova, Maryna, Klein, Dominique, Falquet, Benoît, Fontana, Gabriele Alessandro, Cejka, Petr, Rass, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093310/
https://www.ncbi.nlm.nih.gov/pubmed/27779184
http://dx.doi.org/10.1038/ncomms13157
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author Ölmezer, Gizem
Levikova, Maryna
Klein, Dominique
Falquet, Benoît
Fontana, Gabriele Alessandro
Cejka, Petr
Rass, Ulrich
author_facet Ölmezer, Gizem
Levikova, Maryna
Klein, Dominique
Falquet, Benoît
Fontana, Gabriele Alessandro
Cejka, Petr
Rass, Ulrich
author_sort Ölmezer, Gizem
collection PubMed
description Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts parallel to homologous recombination (HR) in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling. Yen1, but not the HJ resolvases Slx1-Slx4 and Mus81-Mms4, safeguards chromosome segregation by removing replication intermediates that escape Dna2. Post-replicative DNA damage checkpoint activation in Dna2 helicase-defective cells causes terminal G2/M arrest by precluding Yen1-dependent repair, whose activation requires progression into anaphase. These findings explain the exquisite replication stress sensitivity of Dna2 helicase-defective cells, and identify a non-canonical role for Yen1 in the processing of replication intermediates that is distinct from HJ resolution. The involvement of Dna2 helicase activity in completing replication may have implications for DNA2-associated pathologies, including cancer and Seckel syndrome.
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spelling pubmed-50933102016-11-18 Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1 Ölmezer, Gizem Levikova, Maryna Klein, Dominique Falquet, Benoît Fontana, Gabriele Alessandro Cejka, Petr Rass, Ulrich Nat Commun Article Cells have evolved mechanisms to protect, restart and repair perturbed replication forks, allowing full genome duplication, even under replication stress. Interrogating the interplay between nuclease-helicase Dna2 and Holliday junction (HJ) resolvase Yen1, we find the Dna2 helicase activity acts parallel to homologous recombination (HR) in promoting DNA replication and chromosome detachment at mitosis after replication fork stalling. Yen1, but not the HJ resolvases Slx1-Slx4 and Mus81-Mms4, safeguards chromosome segregation by removing replication intermediates that escape Dna2. Post-replicative DNA damage checkpoint activation in Dna2 helicase-defective cells causes terminal G2/M arrest by precluding Yen1-dependent repair, whose activation requires progression into anaphase. These findings explain the exquisite replication stress sensitivity of Dna2 helicase-defective cells, and identify a non-canonical role for Yen1 in the processing of replication intermediates that is distinct from HJ resolution. The involvement of Dna2 helicase activity in completing replication may have implications for DNA2-associated pathologies, including cancer and Seckel syndrome. Nature Publishing Group 2016-10-25 /pmc/articles/PMC5093310/ /pubmed/27779184 http://dx.doi.org/10.1038/ncomms13157 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ölmezer, Gizem
Levikova, Maryna
Klein, Dominique
Falquet, Benoît
Fontana, Gabriele Alessandro
Cejka, Petr
Rass, Ulrich
Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
title Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
title_full Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
title_fullStr Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
title_full_unstemmed Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
title_short Replication intermediates that escape Dna2 activity are processed by Holliday junction resolvase Yen1
title_sort replication intermediates that escape dna2 activity are processed by holliday junction resolvase yen1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5093310/
https://www.ncbi.nlm.nih.gov/pubmed/27779184
http://dx.doi.org/10.1038/ncomms13157
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