Convergence of mitogenic and DNA damage signaling in the G1 phase of the cell cycle

Research into the molecular basis of cancer has a central tenet. Cancer arises from genetic alterations that disconnect growth and differentiation signaling pathways from the machinery that regulates cellular proliferation. In multi-cellular eukaryotes, proliferation is regulated by external signals, such as the availability of growth factors and nutrients and by internal signals, such as those sensing cellular integrity. Cellular stress created either by lack of mitogens or damage to cellular components. such as DNA, stimulates responses that enforce temporal or permanent withdrawal from the cell cycle. Although these stress responses stem from different sources and activate distinct pathways, they converge on the same components of the cell cycle machinery in the G I phase of the cell cycle. This review will highlight and compare aspects of the G I arrest in response to stress generated either by lack of mitogens or damage to DNA. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.