CONTROL OF CELL GROWTH
Tumours develop due to a lack of control in cell growth mechanisms. Cancerous cells accumulate many new mutations which allow them to evade natural mechanisms which detect aberrant cell growth and rapid proliferation. Understanding how normal cells repair mutations or how mutated cells are prevented from undergoing new rounds of cell proliferation is important if new treatments for cancer, and the prevention of metastasis, are to be found. Work to be published in the July issue of Nature Cell Biology (Vol. 3, No. 7, pp. 619-626) by Dr Steve Reed and colleagues (Scripps Research Institute, La Jolla, California) uses the budding yeast to demonstrate the complex co-ordination that occurs in normal cells to regulate replication of DNA and cell division.
Pds1p is a budding yeast protein that must be degraded to allow cell division to continue. Human securin is the homologue of Pds1p, and it has an important role in maintaining chromosome stability as well as a role in cell division. Pds1p degradation depends on whether there is any damage to the DNA or if the machinery necessary for cell division is in place. If there is DNA damage or if cell division cannot proceed, then Pds1p is not degraded.
Reed and colleagues show that Pds1p is the vital protein which determines whether or not cell division continues and is linked to two important checkpoints within the cell. The S-phase checkpoint ensures that all DNA is correctly replicated before cells try to divide, and the G2 checkpoint arrests cell division as soon as there is any damage to the DNA.
Pds1p is involved in both checkpoints, but the regulation of Pds1p is distinct in both cases. Reed and colleagues showed that the yeast protein Mec1p regulates Pds1p levels in the S-phase checkpoint but is regulated by Rad53p and Chk1p in the G2 checkpoint.
The genes involved in budding yeast which control cell proliferation are important in increasing our understanding of how tumours develop. As loss of securin in human cells leads to the development of chromosome instability, the most common cause of human tumour development, this pioneering work in yeast may yet assist in the battle against cancer.
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(C) Nature Cell Biology press release.
Message posted by: Trevor M. D'Souza