DNA damage triggers Golgi dispersal via DNA-PK and GOLPH3

Cell. 2014 Jan 30;156(3):413-27. doi: 10.1016/j.cell.2013.12.023.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Survival
  • Cells, Cultured
  • DNA Damage*
  • DNA-Activated Protein Kinase / metabolism*
  • Golgi Apparatus / metabolism*
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Myosins / metabolism*
  • Phosphorylation
  • Rats
  • Sequence Alignment

Substances

  • GOLPH3 protein, human
  • MYO18A protein, human
  • Membrane Proteins
  • DNA-Activated Protein Kinase
  • Myosins