The G2 DNA Damage Checkpoint Delays Expression of Genes Encoding Mitotic Regulators

Abstract

Transcriptional control of gene expression contributes to the regulation of diverse cellular processes including cell cycle progression and the cellular response to DNA damage. Global gene expression profiling was performed using p53-deficient human cells to identify genes with G(2)/M-specific and DNA damage-responsive expression. Numerous cell cycle-regulated genes were identified, but surprisingly the analysis failed to identify genes activated by ionizing radiation. Instead, significant delays in expression of G(2)/M-specific genes, including known mitotic regulators, were observed following DNA damage. Thus, in the absence of p53, gene induction does not contribute to the G(2) arrest following DNA damage. Rather, the DNA damage checkpoint elicits a G(2) cell cycle arrest, in part, by delaying accumulation of proteins required in mitosis.