A Switch in p53 Dynamics Marks Cells That Escape from DSB-Induced Cell Cycle Arrest.

Journal Article (Journal Article)

Cellular responses to stimuli can evolve over time, resulting in distinct early and late phases in response to a single signal. DNA damage induces a complex response that is largely orchestrated by the transcription factor p53, whose dynamics influence whether a damaged cell will arrest and repair the damage or will initiate cell death. How p53 responses and cellular outcomes evolve in the presence of continuous DNA damage remains unknown. Here, we have found that a subset of cells switches from oscillating to sustained p53 dynamics several days after undergoing damage. The switch results from cell cycle progression in the presence of damaged DNA, which activates the caspase-2-PIDDosome, a complex that stabilizes p53 by inactivating its negative regulator MDM2. This work defines a molecular pathway that is activated if the canonical checkpoints fail to halt mitosis in the presence of damaged DNA.

Full Text

Duke Authors

Cited Authors

  • Tsabar, M; Mock, CS; Venkatachalam, V; Reyes, J; Karhohs, KW; Oliver, TG; Regev, A; Jambhekar, A; Lahav, G

Published Date

  • August 4, 2020

Published In

Volume / Issue

  • 32 / 5

Start / End Page

  • 107995 -

PubMed ID

  • 32755587

Pubmed Central ID

  • PMC7521664

Electronic International Standard Serial Number (EISSN)

  • 2211-1247

Digital Object Identifier (DOI)

  • 10.1016/j.celrep.2020.107995

Language

  • eng

Conference Location

  • United States