Editors' ChoiceCell Cycle

The Pause That Repairs

Science's STKE  30 May 2000:
Vol. 2000, Issue 34, pp. tw8
DOI: 10.1126/stke.2000.34.tw8

When cells acquire DNA damage through exposure to ultraviolet (UV) light, they pause in the cell cycle to allow repair before cell division proceeds. One such checkpoint mechanism acts through the p53 tumor suppressor protein to increase the synthesis of the cyclin-dependent kinase inhibitor p21CIP1/WAF1. Mailand et al. show another mechanism by which cells are prevented from undergoing DNA replication. In cells exposed to UV radiation, the phosphatase Cdc25A (which dephosphorylates and activates Cdk2) becomes ubiquitinated and is degraded in a proteasome-dependent manner. This process causes cells to pause in the G1 phase of the cell cycle before DNA synthesis occurs. Phosphorylation of Cdc25A by the protein kinase Chk1 may target the phosphatase for degradation. This pathway of signaling through Cdc25A and the one mediated by p53 though p21 appear to cooperate to prevent genomic instability. Improper function of either pathway could contribute to genomic damage and formation of cancer cells.

Mailand, N., Falck, J., Lukas, C., Syljuåsen, R.G., Welcker, M., Bartek, J., and Lukas, J. (2000) Rapid destruction of human Cdc25 in response to DNA damage. Science 288: 1425-1429. [Abstract] [Full Text]