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Repair of trapped topoisomerase II covalent cleavage complexes: Novel proteasome-independent mechanisms
https://repo.qst.go.jp/records/77689
https://repo.qst.go.jp/records/77689780c85d0-5aae-4bca-9a31-1c8c45a35d40
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-11-28 | |||||
| タイトル | ||||||
| タイトル | Repair of trapped topoisomerase II covalent cleavage complexes: Novel proteasome-independent mechanisms | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
M, Tsuda
× M, Tsuda× K, Kitamasu× S, Hosokawa× Nakano, Toshiaki× H, Ide× Nakano, Toshiaki |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Topoisomerase II (TOP2) resolves topologically entwined duplex DNA. It generates a transient DNA double-strand break intermediate, known as TOP2 cleavage complex (TOP2cc) that contains a covalent link between TOP2 and the 5′-terminus of the incised DNA duplex. Etoposide, a frontline anticancer drug, freezes the intermediate and forms irreversible TOP2ccs. Tyrosyl-DNA phosphodiesterase 2 (TDP2) is thought to repair irreversible TOP2ccs by hydrolyzing the phosphodiester bond between TOP2 and DNA after the proteasomal degradation of trapped TOP2ccs. However, the functional cooperation between TOP2 and proteasome in the repair of trapped TOP2ccs in vivo remains unknown. In this study, we analyze the repair of etoposide-induced TOP2ccs in wild-type and TDP2-deficient (TDP2–/–) TK6 cells in the absence and presence of MG132, a potent proteasome inhibitor. The results suggested that TOP2ccs were repaired by proteasome-dependent and proteasome-independent pathways. Both proteasome-dependent and proteasome-independent pathways were further subdivided into TDP2-dependent and TDP2-independent pathways, indicating that four pathways operate in the repair of TOP2ccs. In cell survival assays, MG132 increased the etoposide sensitivity of TDP2–/– cells, supporting the TDP2-independent and proteasome-dependent pathway among these multiple repair pathways. We also demonstrated that TDP2 released TOP2 from DNA that contained etoposide-induced TOP2cc without proteolytic degradation in vitro. Taken together, the present findings uncover novel proteasome-independent mechanisms for the repair of TOP2ccs. | |||||
| 書誌情報 |
Nucleosides, Nucleotides & Nucleic Acids 巻 39, 号 1-3, p. 170-184, 発行日 2019-10 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1525-7770 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1080/15257770.2019.1674332 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.tandfonline.com/doi/abs/10.1080/15257770.2019.1674332 | |||||
