Hanover, NH 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 chromosomes precisely, an event that relies on the bi-oriented attachment of chromosomes to spindle microtubules through specialized structures called kinetochores. In the early phases of division, there are numerous errors in how kinetochores bind to spindle microtubules. Normal cells efficiently correct these errors so that chromosomes segregate faithfully. However, cancer cells generally do not correct these errors, resulting in daughter cells 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 compatibilitythat is, looking for the right matchto make sure there are correct attachments and no errors. The old view of
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The Geisel School of Medicine at Dartmouth