The HINT1 tumor suppressor regulates both gamma-H2AX and ATM in response to DNA damage.
The HINT1 tumor suppressor regulates both gamma-H2AX and ATM in response to DNA damage.
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HINT1肿瘤抑制剂响应DNA损伤，调节伽马-H2AX和ATM。
DOI：
10.1083/jcb.200711150
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发表时间：
2008-10-20
期刊：
影响因子：
--
通讯作者：
Weinstein IB
中科院分区：
文献类型：
--
作者：
Li H;Balajee AS;Su T;Cen B;Hei TK;Weinstein IB
Hint1 is a haploinsufficient tumor suppressor gene and the underlying molecular mechanisms for its tumor suppressor function are unknown. In this study we demonstrate that HINT1 participates in ionizing radiation (IR)–induced DNA damage responses. In response to IR, HINT1 is recruited to IR-induced foci (IRIF) and associates with γ-H2AX and ATM. HINT1 deficiency does not affect the formation of γ-H2AX foci; however, it impairs the removal of γ-H2AX foci after DNA damage and this is associated with impaired acetylation of γ-H2AX. HINT1 deficiency also impairs acetylation of ATM and activation of ATM and its downstream effectors, and retards DNA repair, in response to IR. HINT1-deficient cells exhibit resistance to IR-induced apoptosis and several types of chromosomal abnormalities. Our findings suggest that the tumor suppressor function of HINT1 is caused by, at least in part, its normal role in enhancing cellular responses to DNA damage by regulating the functions of both γ-H2AX and ATM.
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影响因子：
16
作者：
Downs, JA;Allard, S;Côté, J
通讯作者：
Côté, J
影响因子：
11.2
作者：
Ishii, Hideshi;Mimori, Koshi;Huebner, Kay
通讯作者：
Huebner, Kay
DOI：
10.1073/pnas.96.4.1403
发表时间：
1999-02-16
影响因子：
11.1
作者：
Kurimasa, A;Ouyang, H;Li, GC
通讯作者：
Li, GC
影响因子：
4.8
作者：
Ajit, Seena K.;Ramineni, Suneela;Young, Kathleen H.
通讯作者：
Young, Kathleen H.
DOI：
10.1073/pnas.93.11.5357
发表时间：
1996-05-28
影响因子：
11.1
作者：
Lima, CD;Klein, MG;Hendrickson, WA
通讯作者：
Hendrickson, WA