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Camptothecin compromises transcription recovery and cell survival against cisplatin and ultraviolet irradiation regardless of transcription-coupled nucleotide excision repair.
Sakasai, Ryo; Wakasugi, Mitsuo; Matsui, Tadashi; Sunatani, Yumi; Saijo, Masafumi; Matsunaga, Tsukasa; Iwabuchi, Kuniyoshi.
Afiliación
  • Sakasai R; Department of Biochemistry I, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan. Electronic address: sakasai@kanazawa-med.ac.jp.
  • Wakasugi M; Laboratory of Human Molecular Genetics, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
  • Matsui T; Department of Biochemistry I, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan.
  • Sunatani Y; Department of Biochemistry I, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan.
  • Saijo M; Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
  • Matsunaga T; Laboratory of Human Molecular Genetics, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan.
  • Iwabuchi K; Department of Biochemistry I, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan. Electronic address: kuni-kmu@kanazawa-med.ac.jp.
DNA Repair (Amst) ; 113: 103318, 2022 May.
Article en En | MEDLINE | ID: mdl-35325630
DNA-damaging anti-cancer drugs are used clinically to induce cell death by causing DNA strand breaks or DNA replication stress. Camptothecin (CPT) and cisplatin are commonly used anti-cancer drugs, and their combined use enhances the anti-tumour effects. However, the mechanism underlying this enhanced effect has not been well studied. In this study, we analysed the combined effect of CPT and cisplatin or ultraviolet (UV) and found that CPT suppresses transcription recovery after UV damage and induces the disappearance of the Cockayne syndrome group B (CSB) protein, a transcription-coupled nucleotide excision repair (TC-NER) factor. This CPT-induced disappearance of CSB expression was suppressed by proteasome and transcription inhibitors. Moreover, CSB ubiquitination was detected after CPT treatment in a transcription-dependent manner, suggesting that the transcription stress caused by CPT induces CSB ubiquitination, resulting in CSB undetectability. However, Cockayne syndrome group A (CSA) and CUL4A were not involved in the CPT-induced CSB undetectability, suggesting that CSB ubiquitination caused by CPT is regulated differently from the UV response. However, cisplatin or UV sensitivity was enhanced by CPT even in CSB- or CSA-knockout cells. Furthermore, the excessive CSB expression, which suppressed CSB ubiquitination, did not cancel the combined effect of CPT. These results suggest that CPT blocks the repair of cisplatin or UV-induced DNA damage regardless of TC-NER status. CPT possibly compromised the alternative repair pathways other than TC-NER, leading to the suppression of transcription recovery and enhancement of cell killing.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: DNA Repair (Amst) Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: DNA Repair (Amst) Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2022 Tipo del documento: Article Pais de publicación: Países Bajos