DNA Damage Response and Metabolic Reprogramming in Health and Disease

Trends Genet. 2020 Oct;36(10):777-791. doi: 10.1016/j.tig.2020.06.018. Epub 2020 Jul 17.


Nuclear DNA damage contributes to cellular malfunction and the premature onset of age-related diseases, including cancer. Until recently, the canonical DNA damage response (DDR) was thought to represent a collection of nuclear processes that detect, signal and repair damaged DNA. However, recent evidence suggests that beyond nuclear events, the DDR rewires an intricate network of metabolic circuits, fine-tunes protein synthesis, trafficking, and secretion as well as balances growth with defense strategies in response to genotoxic insults. In this review, we discuss how the active DDR signaling mobilizes extranuclear and systemic responses to promote cellular homeostasis and organismal survival in health and disease.

Keywords: DNA damage; aging; cancer; disease; metabolism; stress response.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Animals
  • Cellular Reprogramming*
  • Cellular Senescence*
  • DNA Damage*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • DNA Repair*
  • Humans
  • Mutation
  • Neoplasms / genetics*


  • DNA Repair Enzymes