Published online May 7, 2007
doi:10.1083/jcb.1773iti2
The Journal of Cell Biology, Vol. 177, No. 3, 370-
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Leslie
Emi1 ensures timely mitosis
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Without Emi1, nuclei (blue) balloon as they fill with extra DNA.
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Talk about a career change. Di Fiore and Pines report on page 425 that a protein long thought to inhibit mitotic progression actually promotes mitosis and prevents cells from making too many copies of their DNA.
The cell cycle is driven by destruction. To advance to the next stage, a cell demolishes the road blocks that keep progress in check. Flagging these obstacles for destruction is the job of the anaphase promoting complex/cyclosome (APC/C). Its targets include cyclin B1 and securin, which block mitotic progression and anaphase. It was thought that APC/C itself was kept in check by a protein called Emi1. Emi1's breakdown early in mitosis allowed APC/C activation, the argument went.
Emi1's disappearance, however, begins too soon, Di Fiore and Pines now find. By tracking fluorescent Emi1, the authors found that it was degraded at prophase. When the researchers injected cells with indestructible Emi1, the APC/C still fired up. Together, the experiments reveal that demolition of Emi1 isn't what frees the APC/C to start mitosis.
To find out what Emi1 was really doing, the scientists blocked it using RNAi. Cells stalled before reaching mitosis and destroyed their cyclin A and cyclin B1 prematurely. Since these proteins are targets of APC/C, the authors conclude that Emi1 works by suppressing the APC/C during interphase, not mitosis, and helps to protect cyclins A and B1, which are necessary for progress into mitosis.
The Emi1-deficient cells also displayed bulging nuclei, packed with excess DNA. One of Emi1's jobs, the researchers conclude, is to prevent cells from replicating their chromosomes more than once. The results indicate that Emi1 ensures that every round of DNA replication is followed by a round of cell division. But, the findings also reopen the question of what keeps the APC/C in line during mitosis. 
Mitch Leslie
mitchleslie{at}comcast.net
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Emi1 is needed to couple DNA replication with mitosis but does not regulate activation of the mitotic APC/C
- Barbara Di Fiore and Jonathon Pines
J. Cell Biol. 2007 177: 425-437.
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