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Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion
Establishment of sister chromatid cohesion is coupled to DNA replication, but the underlying molecular mechanisms are incompletely understood. DDX11 (also named ChlR1) is a super-family 2 Fe-S cluster-containing DNA helicase implicated in Warsaw breakage syndrome (WABS). Herein, we examined the role...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Public Library of Science
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179184/ https://www.ncbi.nlm.nih.gov/pubmed/30303954 http://dx.doi.org/10.1371/journal.pgen.1007622 |
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author | Cortone, Giuseppe Zheng, Ge Pensieri, Pasquale Chiappetta, Viviana Tatè, Rosarita Malacaria, Eva Pichierri, Pietro Yu, Hongtao Pisani, Francesca M. |
author_facet | Cortone, Giuseppe Zheng, Ge Pensieri, Pasquale Chiappetta, Viviana Tatè, Rosarita Malacaria, Eva Pichierri, Pietro Yu, Hongtao Pisani, Francesca M. |
author_sort | Cortone, Giuseppe |
collection | PubMed |
description | Establishment of sister chromatid cohesion is coupled to DNA replication, but the underlying molecular mechanisms are incompletely understood. DDX11 (also named ChlR1) is a super-family 2 Fe-S cluster-containing DNA helicase implicated in Warsaw breakage syndrome (WABS). Herein, we examined the role of DDX11 in cohesion establishment in human cells. We demonstrated that DDX11 interacts with Timeless, a component of the replication fork-protection complex, through a conserved peptide motif. The DDX11-Timeless interaction is critical for sister chromatid cohesion in interphase and mitosis. Immunofluorescence studies further revealed that cohesin association with chromatin requires DDX11. Finally, we demonstrated that DDX11 localises at nascent DNA by SIRF analysis. Moreover, we found that DDX11 promotes cohesin binding to the DNA replication forks in concert with Timeless and that recombinant purified cohesin interacts with DDX11 in vitro. Collectively, our results establish a critical role for the DDX11-Timeless interaction in coordinating DNA replication with sister chromatid cohesion, and have important implications for understanding the molecular basis of WABS. |
format | Online Article Text |
id | pubmed-6179184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-61791842018-10-19 Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion Cortone, Giuseppe Zheng, Ge Pensieri, Pasquale Chiappetta, Viviana Tatè, Rosarita Malacaria, Eva Pichierri, Pietro Yu, Hongtao Pisani, Francesca M. PLoS Genet Research Article Establishment of sister chromatid cohesion is coupled to DNA replication, but the underlying molecular mechanisms are incompletely understood. DDX11 (also named ChlR1) is a super-family 2 Fe-S cluster-containing DNA helicase implicated in Warsaw breakage syndrome (WABS). Herein, we examined the role of DDX11 in cohesion establishment in human cells. We demonstrated that DDX11 interacts with Timeless, a component of the replication fork-protection complex, through a conserved peptide motif. The DDX11-Timeless interaction is critical for sister chromatid cohesion in interphase and mitosis. Immunofluorescence studies further revealed that cohesin association with chromatin requires DDX11. Finally, we demonstrated that DDX11 localises at nascent DNA by SIRF analysis. Moreover, we found that DDX11 promotes cohesin binding to the DNA replication forks in concert with Timeless and that recombinant purified cohesin interacts with DDX11 in vitro. Collectively, our results establish a critical role for the DDX11-Timeless interaction in coordinating DNA replication with sister chromatid cohesion, and have important implications for understanding the molecular basis of WABS. Public Library of Science 2018-10-10 /pmc/articles/PMC6179184/ /pubmed/30303954 http://dx.doi.org/10.1371/journal.pgen.1007622 Text en © 2018 Cortone et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Cortone, Giuseppe Zheng, Ge Pensieri, Pasquale Chiappetta, Viviana Tatè, Rosarita Malacaria, Eva Pichierri, Pietro Yu, Hongtao Pisani, Francesca M. Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion |
title | Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion |
title_full | Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion |
title_fullStr | Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion |
title_full_unstemmed | Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion |
title_short | Interaction of the Warsaw breakage syndrome DNA helicase DDX11 with the replication fork-protection factor Timeless promotes sister chromatid cohesion |
title_sort | interaction of the warsaw breakage syndrome dna helicase ddx11 with the replication fork-protection factor timeless promotes sister chromatid cohesion |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6179184/ https://www.ncbi.nlm.nih.gov/pubmed/30303954 http://dx.doi.org/10.1371/journal.pgen.1007622 |
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