The dichotomous effects of caffeine on homologous recombination in mammalian cells

DNA Repair (Amst). 2020 Apr:88:102805. doi: 10.1016/j.dnarep.2020.102805. Epub 2020 Feb 7.


This study was initiated to examine the effects of caffeine on the DNA damage response (DDR) and homologous recombination (HR) in mammalian cells. A 5 mM caffeine treatment caused the cell cycle to stall at G2/M and cells eventually underwent apoptosis. Caffeine exposure also induced a strong DDR along with subsequent activation of wildtype p53 protein. An unexpected observation was the caffeine-induced depletion of Rad51 (and Brca2) proteins. Consequently, caffeine-treated cells were expected to be inefficient in HR. However, a dichotomy in the HR response of cells to caffeine treatment was revealed. Caffeine treatment rendered cells significantly better at performing the nascent DNA synthesis that accompanies the early strand invasion steps of HR. Additionally, caffeine treatment increased chromatin accessibility and elevated the efficiency of illegitimate recombination. Conversely, the increase in nascent DNA synthesis did not translate into a higher number of gene targeting events. Thus, prolonged caffeine exposure stalls the cell cycle, induces a p53-mediated apoptotic response and a down-regulation of critical HR proteins, and for reasons discussed, stimulates early steps of HR, but not the formation of complete recombination products.

Keywords: Brca2; Caffeine; Cell cycle; Chromatin accessibility; DNA damage response; DNA repair; Homologous recombination; Illegitimate recombination; Rad51; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics
  • BRCA2 Protein / metabolism
  • Caffeine / pharmacology*
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Chromatin / drug effects
  • Chromatin / metabolism
  • DNA Damage
  • Dose-Response Relationship, Drug
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • G2 Phase Cell Cycle Checkpoints / genetics
  • Homologous Recombination / drug effects*
  • Humans
  • M Phase Cell Cycle Checkpoints / drug effects
  • M Phase Cell Cycle Checkpoints / genetics
  • Nuclear Proteins
  • Rad51 Recombinase / metabolism


  • BCCIP protein, human
  • BRCA2 Protein
  • Calcium-Binding Proteins
  • Cell Cycle Proteins
  • Chromatin
  • Nuclear Proteins
  • Caffeine
  • Rad51 Recombinase

Grants and funding