Editors' ChoiceCell Cycle

Check Out the Checkpoint

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Science Signaling  17 Mar 2009:
Vol. 2, Issue 62, pp. ec98
DOI: 10.1126/scisignal.262ec98

"Job one" for any living organism is to make cells that can reproduce and faithfully distribute chromosomes. Eukaryotic cells not only manage to line up and segregate their chromosomes during cell division but also have a fail-safe mechanism that prevents cell division from proceeding if all of the chromosomes are not lined up appropriately. Herzog et al. provide a glimpse of the molecular machinery that makes this fail-safe mechanism work. At the heart of the mechanism is a ubiquitin ligase complex, the anaphase-promoting complex/cyclosome (APC/C), whose activity is modulated by an activator, Cdc20, or by an inhibitory complex called the mitotic checkpoint complex (MCC), which includes Cdc20 together with other proteins. Proteins were purified from cells in which the mitotic checkpoint was active or inactive, and the structure of APC/C complexes with or without its various partners bound was observed by single-particle electron microscopy. MCC inhibited APC/C by physically obstructing binding of APC/C’s substrates for ubiquitylation and by inducing changes in APC/C that lock it in a more compact conformation.

F. Herzog, I. Primorac, P. Dube, P. Lenart, B. Sander, K. Mechtler, H. Stark, J.-M. Peters, Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science 323, 1477–1481 (2009). [Abstract] [Full Text]