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  1. 原著論文

The complexity of DNA double strand breaks is a critical factor enhancing end-resection

https://repo.qst.go.jp/records/46982
https://repo.qst.go.jp/records/46982
53e07145-82ca-4660-9459-606cef3ff5cb
Item type 学術雑誌論文 / Journal Article(1)
公開日 2014-12-09
タイトル
タイトル The complexity of DNA double strand breaks is a critical factor enhancing end-resection
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 Yajima, Hirohiko

× Yajima, Hirohiko

WEKO 468950

Yajima, Hirohiko

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Fujisawa, Hiroshi

× Fujisawa, Hiroshi

WEKO 468951

Fujisawa, Hiroshi

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Nakajima, Nakako

× Nakajima, Nakako

WEKO 468952

Nakajima, Nakako

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Hirakawa, Hirokazu

× Hirakawa, Hirokazu

WEKO 468953

Hirakawa, Hirokazu

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Jeggo, Penny

× Jeggo, Penny

WEKO 468954

Jeggo, Penny

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Okayasu, Ryuichi

× Okayasu, Ryuichi

WEKO 468955

Okayasu, Ryuichi

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Fujimori, Akira

× Fujimori, Akira

WEKO 468956

Fujimori, Akira

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矢島 浩彦

× 矢島 浩彦

WEKO 468957

en 矢島 浩彦

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藤澤 寛

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WEKO 468958

en 藤澤 寛

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中島 菜花子

× 中島 菜花子

WEKO 468959

en 中島 菜花子

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平川 博一

× 平川 博一

WEKO 468960

en 平川 博一

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岡安 隆一

× 岡安 隆一

WEKO 468961

en 岡安 隆一

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藤森 亮

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WEKO 468962

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抄録
内容記述タイプ Abstract
内容記述 DNA double strand breaks (DSBs) induced by ionizing radiation (IR) are deleterious damages. Two major pathways repair DSBs in human cells, DNA non-homologous end-joining (NHEJ) and homologous recom- bination (HR). It has been suggested that the balance between the two repair pathways varies depending on the chromatin structure surrounding the damage site and/or the complexity of damage at the DNA break ends. Heavy ion radiation is known to induce complex-type DSBs, and the efficiency of NHEJ in repairing these DSBs was shown to be diminished. Taking advantage of the ability of high linear energy transfer (LET) radiation to produce complex DSBs effectively, we investigated how the complexity of DSB end structure influences DNA damage responses. An early step in HR is the generation of 3' -single strand DNA (SSD) via a process of DNA end resection that requires CtIP. To assess this process, we analyzed the level of phosphorylated CtIP, as well as RPA phosphorylation and focus formation, which occur on the exposed SSD. We show that complex DSBs efficiently activate DNA end resection. After heavy ion beam irradiation, resection signals appear both in the vicinity of heterochromatic areas, which is also observed after X-irradiation, and additionally in euchromatic areas. Consequently, ~85% of complex DSBs are sub- jected to resection in heavy ion particle tracks. Furthermore, around 20-40% of G1 cells exhibit resection signals. Taken together, our observations reveal that the complexity of DSB ends is a critical factor reg- ulating the choice of DSB repair pathway and drastically alters the balance toward resection-mediated rejoining. As demonstrated here, studies on DNA damage responses induced by heavy ion radiation provide an important tool to shed light on mechanisms regulating DNA end resection.
書誌情報 DNA Repair

巻 12, 号 11, p. 936-946, 発行日 2013-11
ISSN
収録物識別子タイプ ISSN
収録物識別子 1568-7864
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