Discovery of cell division 'master controller' may improve understanding and treatment of cancer

September 11, 2013

In a study to be published in the journal Nature, two Dartmouth researchers have found that the protein cyclin A plays an important but previously unknown role in the cell division process, acting as a master controller to ensure the faithful segregation of chromosomes during cell division.

Cell division is the process in which cells reproduce by splitting into two identical copies. This process happens trillions of times in an average person's lifetime. To generate two identical copies, cells must separate their precisely, an event that relies on the bi-oriented attachment of chromosomes to spindle through specialized structures called kinetochores. In the early phases of division, there are numerous errors in how kinetochores bind to microtubules. Normal cells efficiently correct these errors so that chromosomes segregate faithfully. However, generally do not correct these errors, resulting in with abnormal numbers of chromosomes, which may help these cancer cells develop resistance to chemotherapy treatments.

In their study, Dartmouth researchers Lilian Kabeche, PhD, and Duane Compton, PhD, show that microtubule attachments at kinetochores are very unstable in early phases of division. The unstable attachments promote the correction of errors by causing a constant detachment, realignment and reattachment of microtubules from kinetochores in the cells as they try to find the correct attachment. Their study found that the protein cyclin A governs this process by keeping the process going until the errors are eliminated.

"An analogy for this process could be dating," said Compton, Senior Associate Dean for Research and professor of biochemistry at Dartmouth's Geisel School of Medicine. "The chromosomes are testing the microtubules for compatibility—that is, looking for the right match—to make sure there are correct attachments and no errors. The old view of this process held that chromosomes and microtubules pair up individually to find the correct attachment, like conventional dating. However, our results show that the system is more like speed dating. All the chromosomes have to try many connections with microtubules in a short amount of time. Then they all make their final choices at the same time. Cyclin A acts like a timekeeper or referee to make sure no one makes bad connections prematurely."

In normal cells, persistent cyclin A expression prevents the stabilization of microtubules bound to kinetochores even in cells with aligned chromosomes. As levels of cyclin A decline, microtubule attachments become stable, allowing the chromosomes to be divided correctly as proceeds. In contrast, in cyclin A-deficient cells, microtubule attachments are prematurely stabilized. Consequently, these cells may fail to correct errors, leading to higher rates of chromosome mis-segregation.

"Many cancer cells continuously mis-segregate their chromosomes," says Kabeche. "The major cause is improper kinetochore–microtubule attachments. Therefore, understanding how kinetochore–microtubule attachments are regulated throughout cell division is important, not only for furthering our understanding of cell division, but also for allowing us to correct these problems in cancer ."

Explore further: Researchers identify potential cancer target

More information: Paper:

Related Stories

Researchers identify potential cancer target

January 16, 2009

( -- Dartmouth Medical School researchers have found two proteins that work in concert to ensure proper chromosome segregation during cell division. Their study is in the January 2009 issue of the journal Nature ...

Fishing games gone wrong

August 18, 2011

When an egg cell is being formed, the cellular machinery which separates chromosomes is extremely imprecise at fishing them out of the cell's interior, scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, ...

Molecular forces are key to proper cell division

January 21, 2013

Studies led by cell biologist Thomas Maresca at the University of Massachusetts Amherst are revealing new details about a molecular surveillance system that helps detect and correct errors in cell division that can lead to ...

Recommended for you

Scientists overcome key CRISPR-Cas9 genome editing hurdle

December 1, 2015

Researchers at the Broad Institute of MIT and Harvard and the McGovern Institute for Brain Research at MIT have engineered changes to the revolutionary CRISPR-Cas9 genome editing system that significantly cut down on "off-target" ...

Trap-jaw ants exhibit previously unseen jumping behavior

December 1, 2015

A species of trap-jaw ant has been found to exhibit a previously unseen jumping behavior, using its legs rather than its powerful jaws. The discovery makes this species, Odontomachus rixosus, the only species of ant that ...

Which came first—the sponge or the comb jelly?

December 1, 2015

Bristol study reaffirms classical view of early animal evolution. Whether sponges or comb jellies (also known as sea gooseberries) represent the oldest extant animal phylum is of crucial importance to our understanding of ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.