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Control of cell growth
Tumours develop because of a lack of control in cell growth mechanisms. Cancerous cells accumulate many mutations, which allow them to evade the natural mechanisms that 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 necessary if new treatments for cancer, and the prevention of metastasis, are to be found. Work published in the July issue of Nature Cell Biology by Steve Reed and colleagues of the Scripps Research Institute, La Jolla, California, uses the budding yeast to show the complex coordination that occurs in normal cells to regulate replication of DNA and cell division. The human protein 'securin' has a role in maintaining chromosome stability, as well as a role in cell division. In budding yeast, the securin homologue Pds1p must be degraded to allow cell division to continue. The degradation of Pds1p 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 that determines whether or not cell division continues, and that its function 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-phase 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. The protein Mec1p regulates Pds1p levels in the S-phase checkpoint, whereas two proteins — Rad53p and Chk1p — regulate Pds1p in the G2 checkpoint. An understanding of the genes that control cell proliferation in budding yeast increases our understanding of how tumours develop. As loss of securin in human cells leads to 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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