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eLife.29953.pdf | 19.9 MB | Adobe PDF | 見る/開く |
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DCフィールド | 値 | 言語 |
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dc.contributor.author | Wakida, Takeshi | en |
dc.contributor.author | Ikura, Masae | en |
dc.contributor.author | Kuriya, Kenji | en |
dc.contributor.author | Ito, Shinji | en |
dc.contributor.author | Shiroiwa, Yoshiharu | en |
dc.contributor.author | Habu, Toshiyuki | en |
dc.contributor.author | Kawamoto, Takuo | en |
dc.contributor.author | Okumura, Katsuzumi | en |
dc.contributor.author | Ikura, Tsuyoshi | en |
dc.contributor.author | Furuya, Kanji | en |
dc.contributor.alternative | 井倉, 正枝 | ja |
dc.contributor.alternative | 井倉, 毅 | ja |
dc.contributor.alternative | 古谷, 寛治 | ja |
dc.date.accessioned | 2017-12-20T01:52:10Z | - |
dc.date.available | 2017-12-20T01:52:10Z | - |
dc.date.issued | 2017-12-19 | - |
dc.identifier.issn | 2050-084X | - |
dc.identifier.uri | http://hdl.handle.net/2433/228267 | - |
dc.description | 二刀流のがん増殖戦略. 京都大学プレスリリース. 2017-12-20. | ja |
dc.description.abstract | Genotoxic stress causes proliferating cells to activate the DNA damage checkpoint, to assist DNA damage recovery by slowing cell cycle progression. Thus, to drive proliferation, cells must tolerate DNA damage and suppress the checkpoint response. However, the mechanism underlying this negative regulation of checkpoint activation is still elusive. We show that human Cyclin-Dependent-Kinases (CDKs) target the RAD9 subunit of the 9-1-1 checkpoint clamp on Thr292, to modulate DNA damage checkpoint activation. Thr292 phosphorylation on RAD9 creates a binding site for Polo-Like-Kinase1 (PLK1), which phosphorylates RAD9 on Thr313. These CDK-PLK1-dependent phosphorylations of RAD9 suppress checkpoint activation, therefore maintaining high DNA synthesis rates during DNA replication stress. Our results suggest that CDK locally initiates a PLK1-dependent signaling response that antagonizes the ability of the DNA damage checkpoint to detect DNA damage. These findings provide a mechanism for the suppression of DNA damage checkpoint signaling, to promote cell proliferation under genotoxic stress conditions. | en |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | eLife Sciences Organisation, Ltd. | en |
dc.rights | © 2017, Wakida et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. | en |
dc.title | The CDK-PLK1 axis targets the DNA damage checkpoint sensor protein RAD9 to promote cell proliferation and tolerance to genotoxic stress | en |
dc.type | journal article | - |
dc.type.niitype | Journal Article | - |
dc.identifier.jtitle | eLife | en |
dc.identifier.volume | 6 | - |
dc.relation.doi | 10.7554/eLife.29953 | - |
dc.textversion | publisher | - |
dc.identifier.artnum | e29953 | - |
dc.identifier.pmid | 29254517 | - |
dc.relation.url | http://www.kyoto-u.ac.jp/ja/research/research_results/2017/171219_1.html | - |
dcterms.accessRights | open access | - |
datacite.awardNumber | 24687023 | - |
datacite.awardNumber | 23131515 | - |
datacite.awardNumber | 25131707 | - |
datacite.awardNumber | 17K07284 | - |
jpcoar.funderName | 日本学術振興会 | ja |
jpcoar.funderName | 日本学術振興会 | ja |
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 |
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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