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dc.contributor.author | Masamsetti, V. Pragathi | en |
dc.contributor.author | Low, Ronnie Ren Jie | en |
dc.contributor.author | Mak, Ka Sin | en |
dc.contributor.author | O’Connor, Aisling | en |
dc.contributor.author | Riffkin, Chris D. | en |
dc.contributor.author | Lamm, Noa | en |
dc.contributor.author | Crabbe, Laure | en |
dc.contributor.author | Karlseder, Jan | en |
dc.contributor.author | Huang, David C. S. | en |
dc.contributor.author | Hayashi, Makoto T. | en |
dc.contributor.author | Cesare, Anthony J. | en |
dc.contributor.alternative | 林, 眞理 | ja |
dc.date.accessioned | 2019-09-25T04:20:00Z | - |
dc.date.available | 2019-09-25T04:20:00Z | - |
dc.date.issued | 2019-09-17 | - |
dc.identifier.issn | 2041-1723 | - |
dc.identifier.uri | http://hdl.handle.net/2433/244141 | - |
dc.description.abstract | Mitotic catastrophe is a broad descriptor encompassing unclear mechanisms of cell death. Here we investigate replication stress-driven mitotic catastrophe in human cells and identify that replication stress principally induces mitotic death signalled through two independent pathways. In p53-compromised cells we find that lethal replication stress confers WAPL-dependent centromere cohesion defects that maintain spindle assembly checkpoint-dependent mitotic arrest in the same cell cycle. Mitotic arrest then drives cohesion fatigue and triggers mitotic death through a primary pathway of BAX/BAK-dependent apoptosis. Simultaneously, a secondary mitotic death pathway is engaged through non-canonical telomere deprotection, regulated by TRF2, Aurora B and ATM. Additionally, we find that suppressing mitotic death in replication stressed cells results in distinct cellular outcomes depending upon how cell death is averted. These data demonstrate how replication stress-induced mitotic catastrophe signals cell death with implications for cancer treatment and cancer genome evolution. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Springer Nature | en |
dc.rights | © The Author(s) 2019. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. | en |
dc.subject | DNA replication | en |
dc.subject | Mitosis | en |
dc.title | Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | Nature Communications | en |
dc.identifier.volume | 10 | - |
dc.relation.doi | 10.1038/s41467-019-12255-w | - |
dc.textversion | publisher | - |
dc.identifier.artnum | 4224 | - |
dc.identifier.pmid | 31530811 | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 16H06176 | - |
datacite.awardNumber | 16H01406 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
jpcoar.funderName.alternative | Japan Society for the Promotion of Science (JSPS) | en |
出現コレクション: | 学術雑誌掲載論文等 |
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