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  1. 原著論文

DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells.

https://repo.qst.go.jp/records/46635
https://repo.qst.go.jp/records/46635
d29e82a2-e034-4746-b13f-9ed2eaa2c3dc
Item type 学術雑誌論文 / Journal Article(1)
公開日 2013-11-26
タイトル
タイトル DNA-PK inhibition causes a low level of H2AX phosphorylation and homologous recombination repair in Medaka (Oryzias latipes) cells.
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 Urushihara, Yusuke

× Urushihara, Yusuke

WEKO 464924

Urushihara, Yusuke

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Kobayashi, Jyunya

× Kobayashi, Jyunya

WEKO 464925

Kobayashi, Jyunya

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Matsumoto, Yoshihisa

× Matsumoto, Yoshihisa

WEKO 464926

Matsumoto, Yoshihisa

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Komatsu, Kenshi

× Komatsu, Kenshi

WEKO 464927

Komatsu, Kenshi

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Oda, Shoji

× Oda, Shoji

WEKO 464928

Oda, Shoji

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Mitani, Hiroshi

× Mitani, Hiroshi

WEKO 464929

Mitani, Hiroshi

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小林 純也

× 小林 純也

WEKO 464930

en 小林 純也

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松本 義久

× 松本 義久

WEKO 464931

en 松本 義久

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小松 賢志

× 小松 賢志

WEKO 464932

en 小松 賢志

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抄録
内容記述タイプ Abstract
内容記述 Nonhomologous end joining (NHEJ) and homologous recombination (HR) are known as DNA double-strand break (DSB) repair pathways. It has been reported that DNA-PK, a member of PI3 kinase family, promotes NHEJ and aberrant DNA-PK causes NHEJ deficiency. However, in this study, we demonstrate that a wild-type cell line treated with DNA-PK inhibitor and a mutant cell line with dysfunctional DNA-PK showed decreased HR efficiency in fish cells (Medaka, Oryzias latipes). Previously, we reported that the radiation-sensitive mutant RIC1 strain has a defect in the Histone H2AX phosphorylation after γ-irradiation. Here, we showed that a DNA-PK inhibitor, NU7026, treatment resulted in significant reduction in the number of γH2AX foci after γ-irradiation in wild-type cells, but had no significant effect in RIC1 cells. In addition, RIC1 cells showed significantly lower levels of DNA-PK kinase activity compared with wild-type cells. We investigated NHEJ and HR efficiency after induction of DSBs. Wild-type cells treated with NU7026 and RIC1 cells showed decreased HR efficiency. These results indicated that aberrant DNA-PK causes the reduction in the number of γH2AX foci and HR efficiency in RIC1 cells. We performed phosphorylated DNA-PKcs (Thr2609) and 53BP1 focus assay after γ-irradiation. RIC1 cells showed significant reduction in the number of phosphorylated DNA-PKcs foci and no deference in the number of 53BP1 foci compared with wild-type cells. These results suggest that low level of DNA-PK activity causes aberrant DNA-PKcs autophosphorylation in RIC1 cells. It is known that 53BP1 is involved in both DNA-PK dependent and independent NHEJ. Therefore we suggest that DNA-PK independent NHEJ repair DSBs under the condition of decreased DNA-PK activity, which causes reduction of HR efficiency.
書誌情報 Biochemical and Biophysical Research Communications

巻 429, 号 3-4, p. 131-136, 発行日 2012-12
ISSN
収録物識別子タイプ ISSN
収録物識別子 0006-291X
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