期刊
CELL
卷 156, 期 3, 页码 413-427出版社
CELL PRESS
DOI: 10.1016/j.cell.2013.12.023
关键词
-
资金
- NIH [T32-DK07541]
- American Cancer Society Postdoctoral Awards [PF-11-027-01-CSM, PF-13-367-01-CDD, 115095-PF-08-228-01-CSM]
- Era of Hope Scholar Award [W81XWH-10-1-0822]
- NIH Director's New Innovator Award [DP2OD004265]
- Burroughs Wellcome Fund Career Award in the Biomedical Sciences
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 overexpression 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据