The fate of p21 CDKN1A in cells surviving UV-irradiation

Abstract

p21 CDKN1A is a critical regulator of cell cycle progression in response to DNA damage. There are conflicting conclusions as to whether p21 CDKN1A levels increase or decrease after ultraviolet (UV)-irradiation and recently it was even reported to disappear entirely following 2.5–30 J m −2 of UV-irradiation in the presence of growth medium. The latter would suggest an alternative mechanism for cell cycle arrest after UV-irradiation, since p21 CDKN1A induction has been considered to be the major mediator of p53-mediated cell cycle arrest after DNA damage. Using physiological UV doses based on cell-killing, we previously observed and here verify that low doses (1.2–6 J m −2) induce p21 CDKN1A immediately after UV-irradiation, though higher doses cause a latency during which p21 CDKN1A levels remain fairly constant before increasing. As expected, p53 induction preceded p21 CDKN1A induction at all doses. Thus, p21 CDKN1A levels after low doses of UV-irradiation may be controlled in a p53-dependent manner without severe reduction. We propose that physiological relevant UV doses should be determined for each target cell type prior to studying UV-induced responses and that p21 CDKN1A is indeed critical for cell cycle arrest in cells that survive UV-irradiation.