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論文
- タイトル
- タイトル（英）
- TRAIP resolves DNA replication-transcription conflicts during the S-phase of unperturbed cells
- 参照URL
- https://researchmap.jp/toyonatsume/published_papers/43158833
- 著者
- 著者（英）
- Shaun Scaramuzza,Rebecca M. Jones,Martina Muste Sadurni,Alicja Reynolds-Winczura,Divyasree Poovathumkadavil,Abigail Farrell,Toyoaki Natsume,Patricia Rojas,Cyntia Fernandez Cuesta,Masato T. Kanemaki,Marco Saponaro,Agnieszka Gambus
- 担当区分
- 概要
- 概要（英）
- Cell division is the basis for the propagation of life and requires accurate duplication of all genetic information. DNA damage created during replication (replication stress) is a major cause of cancer, premature aging and a spectrum of other human disorders. Over the years, TRAIP E3 ubiquitin ligase has been shown to play a role in various cellular processes that govern genome integrity and faultless segregation. TRAIP is essential for cell viability, and mutations in TRAIP ubiquitin ligase activity lead to primordial dwarfism in patients. Here, we have determined the mechanism of inhibition of cell proliferation in TRAIP-depleted cells. We have taken advantage of the auxin induced degron system to rapidly degrade TRAIP within cells and to dissect the importance of various functions of TRAIP in different stages of the cell cycle. We conclude that upon rapid TRAIP degradation, specifically in S-phase, cells cease to proliferate, arrest in G2 stage of the cell cycle and undergo senescence. Our findings reveal that TRAIP works in S-phase to prevent DNA damage at transcription start sites, caused by replication-transcription conflicts.
- 出版者・発行元
- 出版者・発行元（英）
- 誌名
- 誌名（英）
- Nature Communications
- 巻
- 14
- 号
- 1
- 開始ページ
- 5071
- 終了ページ
- 5071
- 出版年月
- 2023年8月21日
- 査読の有無
- 査読有り
- 招待の有無
- 掲載種別
- 研究論文（学術雑誌）
- ISSN
- DOI URL
- https://doi.org/10.1038/s41467-023-40695-y
- 共同研究・競争的資金等の研究課題
研究者
夏目 豊彰
(ナツメ トヨアキ)