RESEARCH HIGHLIGHTS
Cell biology System reboot
An enzyme that helps yeast cells recover from arrested cell division may be relevant to cancer treatment
An enzyme called cyclin-dependent kinase 1 (Cdk1) is essential for budding yeast cells to re-enter the cycle of cell division after it has been halted because of errors in chromosome segregation, according to a new study led by Uttam Surana at the A*STAR Institute of Molecular and Cell Biology in Singapore1
. Multicellular organisms replace worn-out cells through cell
division. Prior to cell division, however, a cell must replicate its chromosomes and segregate the original and the replica on a structure called mitotic spindle, so that each of its daughter cells receive a full complement of genetic materials. One of the key steps in this process is bipolar attachment, during which the chro- mosomes attach themselves to the spindle. Bipolar attachment is monitored closely by a cellular pathway
called the spindle assembly checkpoint, which surveys the integ- rity of the mitotic spindles and prevents the cell from dividing until all the chromosomes are properly attached. This is accompa- nied by high levels of Cdk1 activity, which until now was thought to maintain the arrest of cell division. Surana and his team have now shown that the enzyme does
exactly the opposite. Working with budding yeast Saccharomyces cerevisae, the researchers abolished Cdk1 activity in cells attempt- ing to recover from mitotic arrest by treating the cells with a Cdk1 inhibitor 1NM-PP1, a compound that inhibits cell division by preventing the chromosomes from attaching to the mitotic spindle. As a result of this, the cells failed to recover from the arrested cell division. In a further set of experiments, the researchers revealed that Cdk1 performs two previously unknown functions. First, they showed that the enzyme re-establishes proper attachment of the chromosomes to the mitotic spindle when cells re-enter the division cycle. They also showed that it maintains high levels of a critical regulator called Cdc20, which is known to be essential for segregating the identical pairs of chromosomes before the cell divides. The new findings suggest that Cdk1 may be a target for cancer
therapies. Some chemotherapeutic regimes, for example, use drugs that inhibit the growth of tumors by disrupting mitotic spindle and prevents the cells from dividing by activating the spindle
A*STAR RESEARCH OCTOBER 2011– MARCH 2012
Illustration of budding yeast cells
checkpoint pathway. However, some tumor cells may recover from this inhibition and escape the programmed cell death. “Given the conserved nature of the cell division control circuits,
we might be able to apply the findings from the study of yeasts to human cells,” says Surana. “Blocking Cdk1 activity would prevent recovery and could prolong the arrest of cell division in cancer cells, making them more susceptible to programmed cell death.” ■
1. Liang, H., Lim, H. H., Venkitaraman, A. & Surana, U. Cdk1 promotes kinetochore bi-orientation and regulates Cdc20 expression during recovery from spindle checkpoint arrest. The EMBO Journal 31, 403–416 (2011).
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