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The epithelium specific cell cycle regulator 14‐3‐3sigma is required for preventing entry into mitosis following ultraviolet B
Author(s) -
Vogel Sandra,
Herzinger Thomas
Publication year - 2013
Publication title -
photodermatology, photoimmunology and photomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.736
H-Index - 60
eISSN - 1600-0781
pISSN - 0905-4383
DOI - 10.1111/phpp.12071
Subject(s) - cell cycle , cell cycle checkpoint , mitosis , cdc25a , microbiology and biotechnology , chek1 , dna damage , mitotic catastrophe , cell cycle protein , dna repair , biology , chemistry , cell , dna , biochemistry
Summary Background Deoxyribonucleic acid damage activates cell cycle checkpoints in order to maintain genomic stability. We assessed the role of different checkpoint genes in response to ultraviolet B irradiation. Methods Cell lines expressing a dominant negative mutant of ataxia telangiectasia and R ad3 related ( A tr) protein or overexpressing Cdc25A , cells deficient for 14‐3‐3σ, N ijmegen breakage syndrome ( N bs), or A taxia telangiectasia mutated ( A tm) were treated with ultraviolet B ( UVB ) and harvested after 12 h, 24 h, or 48 h for analysis by flow cytometry. Results Functional loss of A tm, A tr, or N bs did not result in a significant alteration of the cell cycle profile. Overexpression of Cdc25A led to a delayed arrest at the G1/S transition in response to low doses of UVB . Loss of 14‐3‐3σ, a negative cell cycle regulator and downstream target of p53, caused a transient arrest at the G2/M boundary. Conclusions Loss of 14‐3‐3σ sensitizes cells to UVB . After a transient cell cycle arrest, 14‐3‐3σ‐deficient cells die by undergoing mitotic catastrophe. Cdc25A overexpression causes a delayed arrest in response to low doses of UVB . After higher doses, Cdc25A is no longer able to overrun the checkpoint. A tm, A tr, or N bs are not essential for the checkpoint response to UVB , suggesting the existence of redundant signaling pathways.