Protein kinases and their involvement in the cellular responses to genotoxic stress

Cells are constantly subjected to genotoxic stress, and much has been learned regarding their response to this type of stress during the past year. In general, the cellular genotoxic response can be thought to occur in three stages: (1) damage sensing; (2) activation of signal transduction pathways; (3) biological consequences and attenuation of the response. The biological consequences, in particular, include cell cycle arrest and cell death. Although our understanding of the molecular mechanisms underlying cellular genotoxic stress responses remains incomplete, many cellular components have been identified over the years, including a group of protein kinases that appears to play a major role. Various DNA-damaging agents can activate these protein kinases, triggering a protein phosphorylation cascade that leads to the activation of transcription factors, and altering gene expression. In this review, the involvement of protein kinases, particularly the mitogen-activated protein kinases (MAPKs), at different stages of the genotoxic response is discussed.