Quality control mechanisms in cellular and systemic DNA damage responses

Ageing Res Rev. 2015 Sep;23(Pt A):3-11. doi: 10.1016/j.arr.2014.12.009. Epub 2015 Jan 3.


The maintenance of the genome is of pivotal importance for the functional integrity of cells and tissues. The gradual accumulation of DNA damage is thought to contribute to the functional decline of tissues and organs with ageing. Defects in multiple genome maintenance systems cause human disorders characterized by cancer susceptibility, developmental failure, and premature ageing. The complex pathological consequences of genome instability are insufficiently explained by cell-autonomous DNA damage responses (DDR) alone. Quality control pathways play an important role in DNA repair and cellular DDR pathways. Recent years have revealed non-cell autonomous effects of DNA damage that impact the physiological adaptations during ageing. We will discuss the role of quality assurance pathways in cell-autonomous and systemic responses to genome instability.

Keywords: Ageing; DNA damage; DNA repair; Genome stability; Progeroid syndromes; Ubiquitin proteasome system.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Aging / physiology*
  • Animals
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • DNA Damage / genetics*
  • DNA Damage / physiology*
  • Genome, Human / genetics
  • Genome, Human / physiology
  • Genomic Instability
  • Humans
  • Protein Biosynthesis / genetics
  • Protein Biosynthesis / physiology
  • Quality Control