NEW WORK IN CELL DEATH AND DISEASE -OPEN ACCESS
The skin might maintain homeostasis in spite to daily exposure to UV light thanks to this mechanism.
Cell Death & Disease volume 9, Article number: 1094 (2018)
https://www.nature.com/articles/s41419-018-1130-8
Sublethal UV irradiation induces squamous differentiation via a p53-independent, DNA damage-mitosis checkpoint
de Pedro I, Alonso-Lecue P, Sanz-Gómez N, Freije A, Gandarillas A
The epidermis is a self-renewal epithelium continuously exposed to the
genotoxic effects of ultraviolet (UV) light, the main cause of skin
cancer. Therefore, it needs robust self-protective mechanisms facing
genomic damage. p53 has been shown to mediate apoptosis in sunburn cells
of the epidermis. However, epidermal cells daily receive sublethal
mutagenic doses of UV and massive apoptosis would be deleterious. We
have recently unravelled an anti-oncogenic keratinocyte DNA
damage-differentiation response to cell cycle stress. We now have
studied this response to high or moderate single doses of UV
irradiation. Whereas, as expected, high levels of UV induced
p53-dependent apoptosis, moderate levels triggered squamous
differentiation. UV-induced differentiation was not mediated by
endogenous p53. Overexpression of the mitosis global regulator FOXM1
alleviated the proliferative loss caused by UV. Conversely,
knocking-down the mitotic checkpoint protein Wee1 drove UV-induced
differentiation into apoptosis. Therefore, the results indicate that
mitosis checkpoints determine the response to UV irradiation. The
differentiation response was also found in cells of head and neck
epithelia thus uncovering a common regulation in squamous tissues upon
chronic exposure to mutagens, with implications into homeostasis and
disease.On the press
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