Zhu et al. show that DNA-damage-induced, PIKK-mediated Ser784 phosphorylation is a specific enhancer of VCP function in chromatin-associated protein degradation. Phospho-Ser784-VCP is required for DNA repair, checkpoint signaling, and cell survival in response to a broad range of genotoxins and correlates with poor outcome among chemotherapy-treated breast cancer patients.
- DNA damage response
- K48-linked polyubiquitin
- chromatin-associated degradation