DNA damage responses in skin biology--implications in tumor prevention and aging acceleration

J Dermatol Sci. 2009 Nov;56(2):76-81. doi: 10.1016/j.jdermsci.2009.09.001. Epub 2009 Sep 24.

Abstract

UV irradiation is the main etiological cause of most types of skin cancers and can accelerate skin photoaging. UV irradiation results in several types of DNA damage in eukaryotic cells, such as DNA single strand breaks, DNA interstrand cross-links, and nucleotide base modifications. In response to such DNA damages, mammalian cells exert DNA damage responses including cell cycle checkpoints, well-developed DNA repair, apoptosis and premature senescence to prevent genomic instability. Cell cycle checkpoints are important surveillance systems to maintain genomic integrity. Once checkpoint systems sense the abnormal chromosomal DNA structures, they execute cell cycle arrest through inhibiting the activity of cell cycle regulators and coordinate it with the DNA repair process. Checkpoint responses also execute cellular senescence when cells sense unrepairable and extensive chromosomal abnormalities. Senescent cells are no longer able to divide despite remaining viable for long periods of time, metabolically active, but functionally impaired. Accumulation of senescent cells in skin results in harmful consequences such as skin aging. Therefore, skin photoaging is thought to be a phenotypic hallmark responsible for one of the major mechanisms against skin carcinogenesis. In this review, changes in chromatin modification in response to UV and the molecular mechanisms accelerating aging phenotypes are discussed.

Publication types

  • Portrait
  • Review

MeSH terms

  • Animals
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle / genetics
  • Cell Cycle / radiation effects
  • Cell Cycle Proteins / metabolism
  • Cellular Senescence / genetics
  • Cellular Senescence / radiation effects
  • Checkpoint Kinase 1
  • Chromatin Assembly and Disassembly / radiation effects
  • DNA Damage*
  • DNA Repair*
  • Enzyme Activation
  • Humans
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / radiation effects
  • Skin / metabolism
  • Skin / pathology
  • Skin / radiation effects*
  • Skin Aging / genetics
  • Skin Aging / radiation effects*
  • Skin Neoplasms / etiology
  • Skin Neoplasms / genetics
  • Skin Neoplasms / prevention & control*
  • Ultraviolet Rays / adverse effects*

Substances

  • Cell Cycle Proteins
  • Protein Kinases
  • ATR protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Checkpoint Kinase 1
  • Protein Serine-Threonine Kinases