Focus | January 27, 2006


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	January 27, 2006 SYSTEMS BIOLOGY: When It Comes to Cell Cycle, Tail Wags Dog The cell cycle is powered by the precisely ordered activation and deactivation of dozens of different regulatory proteins. The anaphase-promoting complex (APC) helps drive the process because it sequentially tags proteins with ubiquitin, setting them up for destruction by the proteasome. It is unclear, however, how the APC manages to modify proteins in the correct order. In the Jan. 13 Cell, researchers (left to right) Michael Rape (pronounced RA-pa), Marc Kirschner, and Sashank Reddy report that proteins degraded earliest in the cycle are the least likely to dissociate from the APC once bound to it. Proteins degraded later dissociate readily. This “kinetic proofreading” ensures that the early proteins, such as geminin and securin, are the first to receive a full complement of ubiquitin and fall victim to the proteasome.
	LONGEVITY: Loss of Sirtuin Protein Seen to Cut Life Short Ever since the protein Sir2 was shown to make yeast live longer, scientists have been eager to study Sir2’s counterparts in mammals. Mammals have seven genes that are homologues to Sir2, called sirtuins, and only one has been studied in detail. Now a study led by the lab of Frederick Alt offers the first description of how a second member of the sirtuin family, SIRT6, functions in the body. In the Jan. 27 Cell, Alt’s team shows that SIRT6 seems to play a role in repairing DNA damage, and mice that lack the gene display signs of premature aging.
	BIOLOGICAL CHEMISTRY: DNA Replication Machinery Sows Seeds of Own Demise A dividing cell needs to be fussier than an honest accountant about doubling its DNA. To copy its genome once and only once, the molecular replication machinery contains its own internal auditing device, report Emily Arias and Johannes Walter in the January Nature Cell Biology. They discovered that a protein essential for assembling the DNA copying machinery is methodically routed to a cellular trash bin by the activated machine, preventing the production of multiple copies.