DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3.
DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3.
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DOI：
10.1016/j.cell.2013.12.023
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发表时间：
2014-01-30
期刊：
影响因子：
64.5
通讯作者：
Field SJ
中科院分区：
文献类型：
--
作者：
Farber-Katz SE;Dippold HC;Buschman MD;Peterman MC;Xing M;Noakes CJ;Tat J;Ng MM;Rahajeng J;Cowan DM;Fuchs GJ;Zhou H;Field SJ
DNA 损伤的反应调节 DNA 修复、转录和细胞周期等核过程，现已得到深入研究。然而，人们对细胞质对 DNA 损伤的反应知之甚少。在这里，我们证明 DNA 损伤会引发高尔基体的剧烈重组，导致其分散在整个细胞质中。我们进一步表明，DNA 损伤诱导的高尔基体分散需要 GOLPH3/MYO18A/F-肌动蛋白和 DNA 损伤蛋白激酶 DNA-PK。为了响应 DNA 损伤，DNA-PK 磷酸化 GOLPH3，从而增加与 MYO18A 的相互作用，从而对高尔基体施加张力。通过去除 DNA-PK、GOLPH3 或 MYO18A 来干扰高尔基体 DNA 损伤反应会降低 DNA 损伤后的存活率，而正如在人类癌症中经常观察到的那样，GOLPH3 的过度表达赋予对 DNA 损伤剂杀死的抵抗力。 DNA 损伤诱导的高尔基体反应的鉴定揭示了一条意想不到的途径，通过 DNA-PK、GOLPH3 和 MYO18A 调节 DNA 损伤后的细胞存活。
The response to DNA damage, which regulates nuclear processes such as DNA repair, transcription, and cell cycle, has been studied thoroughly. However, the cytoplasmic response to DNA damage is poorly understood. Here, we demonstrate that DNA damage triggers dramatic reorganization of the Golgi, resulting in its dispersal throughout the cytoplasm. We further show that DNA-damage-induced Golgi dispersal requires GOLPH3/MYO18A/F-actin and the DNA damage protein kinase, DNA-PK. In response to DNA damage, DNA-PK phosphorylates GOLPH3, resulting in increased interaction with MYO18A, which applies a tensile force to the Golgi. Interference with the Golgi DNA damage response by depletion of DNA-PK, GOLPH3, or MYO18A reduces survival after DNA damage, whereas over-expression of GOLPH3, as is observed frequently in human cancers, confers resistance to killing by DNA-damaging agents. Identification of the DNA-damage-induced Golgi response reveals an unexpected pathway through DNA-PK, GOLPH3, and MYO18A that regulates cell survival following DNA damage.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
3.3
作者：
Hammond, AT;Glick, BS
通讯作者：
Glick, BS
DOI：
10.1083/jcb.200208013
发表时间：
2002-11-25
期刊：
The Journal of cell biology
影响因子：
--
作者：
Chiu R;Novikov L;Mukherjee S;Shields D
通讯作者：
Shields D
GOLPH3 过表达与临床 N0 口腔舌癌患者的肿瘤进展和不良预后相关
影响因子：
7.4
作者：
Li H;Guo L;Chen SW;Zhao XH;Zhuang SM;Wang LP;Song LB;Song M
通讯作者：
Song M
影响因子：
16
作者：
Ciccia A;Elledge SJ
通讯作者：
Elledge SJ