Published 13 March 2006. doi:10.1083/jcb.1726iti1
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 172, Number 6, 785-785
Exit without separase
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Liver cells without Separase (right) become large and polyploid.
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Centromere disjunction is not required for mouse cells to exit mitosis, report Wirth et al. (page 847) and Kumada et al. (page 835).
Work in flies and fission yeast has previously shown that cells lacking separase, an enzyme required to break the cohesive force that holds sister chromatids together through anaphase, exited mitosis despite having failed to separate chromosomes. The daughter cells in yeast carried broken chromosome and died as a result, whereas fly daughter cells had reduplicated chromosomes and were initially viable.
The two teams have now found that the same thing happens in mouse cells that lack separase. In the absence of separase activity, most of the cohesin dissipated as expected from chromosome arms, but the enzyme was required to remove the cohesive glue at the centromeres themselves.
Embryos lacking separase die early in development, but some cell types were tolerant of the polyploidy caused by the enzyme's absence. For example, Wirth et al. found that mice regenerated functional liver tissue in the absence of separase and appeared indifferent to the cells' polyploid status even after multiple rounds of division. By contrast, bone marrow cells did not survive in the absence of separase.
While Kumada et al. are working to sort out the details of timing defects in double mutants that lack one copy of separase and both copies of securin, an inhibitor of separase, Wirth et al. are now looking to see what happens in oocytes that lack separase. They think precocious separation of sister centromeres might be responsible for trisomies and that separase might be a culprit.
Rabiya S. Tuma
rabiya{at}nasw.org
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