We are often questioned over the functions of endoreplication. This has been addressed in good research models, such as drosophila or plant epidermis [3, 56]. Briefly, the potential functions in which mitotic slippage and endoreplication might be involved in human skin are as follows:
1- By accumulating growth without division, suprabasal keratinocytes become larger [4, 54].
2- By amplifying gene copy number, epidermal cells can more efficiently produce RNA and proteins needed for the differentiated phenotype [57].
3- By increasing cellular size, it limits the number of cells needed to cover the same surface, thus diminishing the number of cell divisions in the basal layer and the probability of transforming mutations (Fig. 1b; [22]).
4- By uncoupling the initiation of differentiation from cell cycle arrest, the epidermis, permanently exposed to DNA insult, possesses a mechanism to suppress proliferation and expel cells through squamous differentiation even if the nucleus is actively cycling.
Endoreplication unravels a dynamic link between active cell cycle and the initiation of differentiation through mitosis checkpoints that might function as an anti-oncogenic self-defense mechanism (Fig. 1b and Fig. S2b). Our results show not only that differentiating keratinocytes continue on cycle, but furthermore that cell cycle hyperactivation leads to differentiation [22, 47]. Thus, as a continuum, cell growth is translated first into proliferation and second into differentiation (Fig. 2a,b and Fig. S2b).
As far as a hundred years ago, Loeb and Addison suggested that a relationship existed between the skin structure and its proliferative power (Quotation S4; [7, 85, 86]). Endoreplication can make this relationship by automatically coordinating proliferation with differentiation as an orchestra, even upon hyperproliferative signals (Fig. 1b).
In EXPERIMENTAL DERMATOLOGY
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Cycling up the epidermis: reconciling 100 years of debate
Article first published online: 26 DEC 2013
DOI: 10.1111/exd.12287
(From the Skin Cancer Foundation Site)
