Cancer cells are growing without control and it is therefore important to understand the mechanisms limiting the growth of normal cells.
Before a cell can divide it must make a new set of chromosomes, so that both daughter cells receive the same genetic information as their mother. The period of chromosome replication is called the S phase and marks the start of a long series of complex reactions ending in cell division. The whole process is called the cell cycle, since after dividing, the cells can again engage in another round of chromosome replication and subsequent cell division. By deciding to do chromosome replication the cells are committed to cell division, and therefore this decision is of paramount importance for cell proliferation. The majority of cancer cells have defective regulation of the entry into S phase.
It is well known that the cell cycle is stopped when the DNA is damaged by mechanisms called checkpoints. Tvegård et al describes a completely new principle for regulation of S phase. They show that when fission yeast cells are exposed to ultraviolet light they delay entry into the cell cycle, as predicted. Surprisingly, the mechanism of inhibition does not depend on classical checkpoint proteins, but rather to a protein kinase, called Gcn2, that is normally regulating the growth rate (protein synthesis). Therefore, the findings suggest a possible link between general cell growth and progression through the cell cycle.
Tvegård T, Soltani H, Skjølberg HC, Krohn M, Nilssen EA, Kearsey SE, Grallert B, Boye E. A novel checkpoint mechanism regulating the G1/S transition.
Genes Dev. 2007 Mar 15;21(6):649-54. Erratum in: Genes Dev. 2007 May 15;21(10):1273.
Nilssen EA, Synnes M, Tvegård T, Vebø H, Boye E, Grallert B. Germinating fission yeast spores delay in G1 in response to UV irradiation. BMC Cell Biol. 2004 Oct 21;5(1):40.
Tvegård T and Grallert B. Tor regulates translation initiation through eIF2a phosphorylation (manuscript)