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An insecure role for Securin in chromosome segregation

PLOS

A critical aspect of cell division, or mitosis, is that the progeny cells must receive the full complement of chromosomes. Failure of this mechanism, which sometimes happens in cancer cells, leads to rampant chromosome loss and mutations that encourage proliferation and increase instability. Understanding how normal cells unerringly transmit a full chromosome set to their daughters has long been an important part of the fight against cancer.

In a new study published online in the open-access journal PLoS Biology, Katrin Pfleghaar, Michael Speicher, and colleagues reinvestigate the cell's ability to undergo mitosis when missing a key protein, securin. Securin is a chaperone protein that regulates an enzyme that initiates the segregation of the sister chromatids during mitosis. They found that, contrary to previous reports, human cells devoid of the securin protein, which initially suffer widespread chromosome losses, can actually recover after a certain time has passed. In fact, cells with abnormal mitoses and chromosome counts became rarer until, after a few weeks, the cells appeared indistinguishable from their relatives with an intact securin gene. Pfleghaar and her colleagues speculate that securin normally plays an important role in mitoses, but that in its absence, cells tap into compensatory mechanisms to restore proper chromosome segregation.

The implications for cancer treatment are potentially great, as mathematical models of cancer growth do not usually include the possibility that cell populations might recover from chromosomal instability. In addition, such recovery from securin loss, like that seen here, might interfere with therapies that aim to kill cancer cells by exacerbating their chromosome losses.

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Pfleghaar K, Heubes S, Cox J, Stemmann O, Speicher MR (2005) Securin is not required for chromosomal stability in human cells. PLoS Biol 3(12): e416.

Contact:
Michael R. Speicher
Technical University Munich
Institute of Human Genetics
Trogerstr. 32
Munich, Germany 81675
49-894-140-6386
49-894-140-6382 (fax)
speicher@humangenetik.med.tu-muenchen.de

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