Involvement of p16CDKN2A in cell cycle delays after low dose UV irradiation

Mutat Res. 1998 Nov 9;422(1):43-53. doi: 10.1016/s0027-5107(98)00174-2.


Ultraviolet (UV) radiation contributes to the aetiology of melanoma, but the precise mechanistic details are still unclear. The CDKN2A gene which is associated with familial and sporadic melanoma, encodes a tumour suppressor, p16. We have previously shown that in response to low doses of UV radiation the level of p16 increases, and that this correlates with a G2 delay. Here we report that in melanoma cell lines which do not express p16, or express a mutant p16, no G2 delay is observed in response to UV. The loss of functional p16 also correlates with an increase in DNA damage as judged by increased numbers of bi- and multinuclear cells and cells containing 1-2 micronuclei following UV irradiation. This work provides a further link between UV radiation, CDKN2A and melanoma, suggesting that the functional inactivation of CDKN2A disrupts a p16-dependent G2 cell cycle checkpoint, thus contributing to the development of this neoplasm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / physiology
  • Cell Cycle / radiation effects*
  • Cell Division / radiation effects
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Cyclin-Dependent Kinase Inhibitor p16 / radiation effects
  • Gene Deletion
  • Genes, p16*
  • HeLa Cells
  • Humans
  • Keratinocytes / cytology
  • Keratinocytes / radiation effects
  • Kinetics
  • Melanoma / genetics
  • Time Factors
  • Tumor Cells, Cultured
  • Ultraviolet Rays*


  • Cyclin-Dependent Kinase Inhibitor p16