DNA Damage in Stem Cells

I. Vitale, G. Manic, R. De Maria, G. Kroemer, L. Galluzzi

Research output: Contribution to journalArticle

Abstract

Both embryonic and adult stem cells are endowed with a superior capacity to prevent the accumulation of genetic lesions, repair them, or avoid their propagation to daughter cells, which would be particularly detrimental to the whole organism. Inducible pluripotent stem cells also display a robust DNA damage response, but the stability of their genome is often conditioned by the mutational history of the cell population of origin, which constitutes an obstacle to clinical applications. Cancer stem cells are particularly tolerant to DNA damage and fail to undergo senescence or regulated cell death upon accumulation of genetic lesions. Such a resistance contributes to the genetic drift of evolving tumors as well as to their limited sensitivity to chemo- and radiotherapy. Here, we discuss the pathophysiological and therapeutic implications of the molecular pathways through which stem cells cope with DNA damage.
Original languageEnglish
Pages (from-to)306-319
Number of pages14
JournalMolecular Cell
Volume66
Issue number3
DOIs
Publication statusPublished - May 4 2017

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Keywords

  • DNA mismatch repair
  • DNA synthesis
  • autophagy
  • base excision repair
  • homologous recombination
  • non-homologous end joining
  • nucleotide excision repair
  • p53
  • reactive oxygen species
  • regulated cell death translation

Cite this

Vitale, I., Manic, G., Maria, R. D., Kroemer, G., & Galluzzi, L. (2017). DNA Damage in Stem Cells. Molecular Cell, 66(3), 306-319. https://doi.org/S1097-2765(17)30236-8 [pii]