Cerebral cortex: Sizing up the columns

摘要

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 Rad3 related (Atr) protein or overexpressing Cdc25A, cells deficient for 14-3-3σ, Nijmegen breakage syndrome (Nbs), or Ataxia telangiectasia mutated (Atm) were treated with ultraviolet B (UVB) and harvested after 12h, 24h, or 48h for analysis by flow cytometry. Results: Functional loss of Atm, Atr, or Nbs 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. Atm, Atr, or Nbs are not essential for the checkpoint response to UVB, suggesting the existence of redundant signaling pathways.