Balancing self-renewal against genome preservation in stem cells: How do they manage to have the cake and eat it too?

Cell Mol Life Sci. 2016 May;73(9):1803-23. doi: 10.1007/s00018-016-2152-y. Epub 2016 Feb 17.


Stem cells are endowed with the awesome power of self-renewal and multi-lineage differentiation that allows them to be major contributors to tissue homeostasis. Owing to their longevity and self-renewal capacity, they are also faced with a higher risk of genomic damage compared to differentiated cells. Damage on the genome, if not prevented or repaired properly, will threaten the survival of stem cells and culminate in organ failure, premature aging, or cancer formation. It is therefore of paramount importance that stem cells remain genomically stable throughout life. Given their unique biological and functional requirement, stem cells are thought to manage genotoxic stress somewhat differently from non-stem cells. The focus of this article is to review the current knowledge on how stem cells escape the barrage of oxidative and replicative DNA damage to stay in self-renewal. A clear statement on this subject should help us better understand tissue regeneration, aging, and cancer.

Keywords: Aging; Cancer stem cells; DNA repair; Immortal strand; Nucleostemin; Oxidative stress; Replicative stress; Telomere; Translesion synthesis; Tumor progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • DNA Damage
  • DNA Repair
  • Genome*
  • Humans
  • Nuclear Proteins / metabolism
  • Oxidative Stress
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Telomere / metabolism


  • Nuclear Proteins