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DSBs are rejoined or repaired by two major pathways in mammalian cells: i.e. homologous recombination (HR) and non-homologous end-joining (NHEJ). DNA-PK is a nuclear, serine/threonine protein kinase consisting of three subunits of DNA-PKcs, Ku70 and Ku80, and involved in the NHEJ, V(D)J recombination and modulation of transcription [1]. Cells lacking DNA-PKcs activity are highly sensitive to DSBs-inducing agents such as ionizing radiations [2]. Douglas et al [3] identified 4 phosphorylation sites in the DNA-PKcs protein: i.e. Thr-2609, Ser-2612, Thr-2638 and Thr-2647. These sites were autophosphorylated with own DNA-PKcs. Chan et al [4] demonstrated that autophosphorylation of DNA-PKcs was required for the rejoining of DSBs. \nRadiation sensitivities of 31 human esophageal squamous cell carcinoma (ESCC) cell lines were investigated with a colony-formation assay. There was a large variation in radiosensitivity among 31 cell lines. 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A deficiency in the phosphorylation of DNA-PKcs in a radiosensitive human ESCC cell line
https://repo.qst.go.jp/records/53716
https://repo.qst.go.jp/records/5371669177dff-266e-46a5-b090-7ce35535f2b6
Item type | 会議発表論文 / Conference Paper(1) | |||||
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公開日 | 2006-06-13 | |||||
タイトル | ||||||
タイトル | A deficiency in the phosphorylation of DNA-PKcs in a radiosensitive human ESCC cell line | |||||
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_5794 | |||||
資源タイプ | conference paper | |||||
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 |
Ban, Sadayuki
× Ban, Sadayuki× Okayasu, Ryuichi× Sagara, Masashi× Michikawa, Yuichi× Umetsu, Atsushi× Sakurai, Akio× Ishikawa, Ken-ichi× Okabe, Atsushi× Shimada, Yutaka× Inazawa, Jouji× Imai, Takashi× 伴 貞幸× 岡安 隆一× 相良 雅史× 道川 祐市× 梅津 篤× 櫻井 亜希子× 石川 顕一× 岡部 篤史× 今井 高志 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | DNA double strand breaks (DSBs) are the most deleterious and lethal form of DNA damage. DSBs are rejoined or repaired by two major pathways in mammalian cells: i.e. homologous recombination (HR) and non-homologous end-joining (NHEJ). DNA-PK is a nuclear, serine/threonine protein kinase consisting of three subunits of DNA-PKcs, Ku70 and Ku80, and involved in the NHEJ, V(D)J recombination and modulation of transcription [1]. Cells lacking DNA-PKcs activity are highly sensitive to DSBs-inducing agents such as ionizing radiations [2]. Douglas et al [3] identified 4 phosphorylation sites in the DNA-PKcs protein: i.e. Thr-2609, Ser-2612, Thr-2638 and Thr-2647. These sites were autophosphorylated with own DNA-PKcs. Chan et al [4] demonstrated that autophosphorylation of DNA-PKcs was required for the rejoining of DSBs. Radiation sensitivities of 31 human esophageal squamous cell carcinoma (ESCC) cell lines were investigated with a colony-formation assay. There was a large variation in radiosensitivity among 31 cell lines. In particular, the radiation sensitivity of one cell line (KYSE190) was distinct from a cluster of radiation sensitivities of other 30 cell lines. In order to understand the mechanism behind this hypersensitivity, we investigated the expression of ATM and DNA-PKcs proteins with a western-blotting method and the phosphorylation of DNA-PKcs with a immunohistochemical staining methd. The phosphorylation of DNA-PKcs was not observed in KYSE190 cells. No mutation was detected in the four phosphorylation sites, but one base change in FAT domain of DNA-PKcs gene was observed. These data seem to indicate that the high radiosensitivity of KYSE 190 cells results from the defect in the autophosphorylation of the DNA-PKcs protein. |
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書誌情報 |
Proceedings of the Japan-France Workshop on Radiobiology and Isotopic Imaging p. 62-66, 発行日 2004-06 |