"We had previously demonstrated that the p53 gene product--the most commonly mutated gene in human cancer--controls cell-cycle arrest in response to damage," says Kastan. In this paper the authors have identified two new participants in the damage-response pathway, using cells from patients with ataxia-telangiectasia [AT], a disease characterized by hypersensitivity to radiation and high susceptibility to cancer.
"In normal cells, when DNA is damaged by ionizing radiation, the p53 protein levels rise rapidly and arrest the cell cycle," explains Kastan. When the cell cycle is not arrested, cells continue to replicate, which, in the face of damaged DNA, could ultimately contribute to the development of tumors. The investigators found that in AT cells the levels of p53 following radiation were abnormally low, thus indicating an additional factor--the AT gene--in the pathway.
"While previously it was not known when the cell used p53 to halt the cell cycle, our data showed ...
