Ultraviolet light induces the sustained unscheduled expression of cyclin E in the absence of functional p53

• Published in: Cell cycle (Georgetown, Tex.) Vol. 8; no. 18; pp. 2998 - 3005
• Main Authors: Stubbert, Lawton J., Spronck, Jennifer C., Hamill, Jeff D., McKay, Bruce
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 15.09.2009
• Subjects: Binding; Biology; Bioscience; Calcium; Cancer; Cell; Cycle; Landes; Organogenesis; Proteins
• ISSN: 1538-4101; 1551-4005
• DOI: 10.4161/cc.8.18.9614

Cell cycle progression is regulated through changes in the activity of cyclin-dependent kinases that are, in turn, regulated by the expression of their respective cyclin partners.  In primary cells, cyclin E expression increases through the G1 phase of the cell cycle and peaks near the G1/S boundary.  The unscheduled expression of cyclin E in primary human fibroblasts leads to chromosomal instability that is greatly increased by loss of the p53 tumour suppressor.  Intriguingly, ultraviolet light (UV), the most prevalent environmental carcinogen, is similarly known to induce chromosomal instability more dramatically in the absence of p53.  Here we report that UV light transiently increased the expression of cyclin E in normal human fibroblasts.  Strikingly, cyclin E levels remained elevated for an extended period of time in the absence of functional p53.  UV-induced cyclin E expression was not restricted to the G1/S boundary but remained elevated throughout S phase and this correlated with a massive accumulation of p53-deficient fibroblasts in this phase of the cell cycle.  Forced expression of cyclin E alone was insufficient to cause a similar S phase arrest but forced expression of cyclin E led to an increase in the proportion of UV-irradiated cells in S phase.  The present work suggests that p53 affects S phase progression following UV exposure by preventing the sustained unscheduled expression of cyclin E and that this may limit the clastogenic and carcinogenic effects of UV light.