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UVa researchers describe method of protecting chromosomes during cell division

CHARLOTTESVILLE, Va., Mar. 4 One hallmark of most cancer cells is that they have the incorrect number of chromosomes, a state called aneuploidy. Now, researchers at the University of Virginia Health System, writing in a recent issue of the journal Current Biology, think they know how cells protect themselves from aneuploidy when they divide in a process known as mitosis. "During mitosis, the cell divides replicated chromosomes to two daughter cells. We are studying a mitotic system that ensures that each cell receives the right number of chromosomes," said article co-author Todd Stukenberg, assistant professor of biochemistry and molecular genetics at U.Va.

To function effectively, a human cell must have one copy of 46 different chromosomes, each containing two exact copies of a long DNA strand packaged into two sister chromatids. When a cell divides, it forms a spindle made up of thin polymers called microtubules extending from opposing sides of the cell.

During division, however, the cell is faced with a monumental sorting problem since all chromosomes look alike. So, nature has devised a solution microtubules from one side of the cell must bind one chromatid, while microtubules from the other side bind the other. The cell then uses these microtubule connections to pull the two sister chromatids to opposite sides of the cell, and the cell is then cleaved between the two DNA masses. Aneuploidy may occur when this process goes awry and microtubules from opposite sides of the cell bind the same chromatid, which becomes stuck since it is pulled in both directions, Stukenberg said.

According to the study, researchers at the U.Va.'s Department of Biochemisty and Molecular Genetics, working with colleagues in U.Va.'s Department of Chemistry, have uncovered a mechanism that could correct these improper attachments proteins that release improper microtubule attachments. A protein called Aurora B loads a substance called MCAK (mi
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Contact: Bob Beard
reb8e@virginia.edu
434-982-4490
University of Virginia Health System
4-Mar-2004


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