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Two central mysteries in genome inheritance solved at UCSD

pending on the species, requires specialized protein polymers called microtubules.

"After the genome is replicated, microtubule polymers build a spindle-shaped structure whose two ends collect precisely half of the duplicated genome before the cell is pinched in the middle to form two cells," said Desai. Chromosomes connect to the spindle microtubule polymers during this time, and interfering with this connection ?using drugs that bind to microtubule polymers ?is a common chemotherapy strategy used to target and curtail rapidly dividing cancer cells. While scientists have known that breakdown of this connection could stop the proliferation of cancerous cells, they didn't know how the connection itself was established.

Using a biochemical approach, Desai and postdoctoral fellow Iain Cheeseman, Ph.D., have solved this mystery. In the December 1 paper, they identified a protein group that forms the chromosome-spindle connection and is present in even the simplest single-celled organisms, indicating that its role in genome distribution is ancient and widely conserved. Identification of this protein group provides scientists with new drug targets in cancer cells.

"Right now, drugs used in chemotherapy affect microtubules in all the body's cells, resulting in adverse side effects, like nerve pain and loss of sensation ," said Desai. "If we could specifically target dividing cells, we should improve on current chemotherapy to treat the cancer with fewer side effects."

The second paper from Desai's research group, to be published in the December 15 issue of Cell, identifies a different type of connection between chromosomes and microtubule polymers, which operates to discriminate between correct and incorrect chromosome-spindle attachments.

Each replicated chromosome is comprised of a pair of identical sister chromatids, generated by the copying of the parental DNA strand. These pairs are held together during the early
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Source:University of California - San Diego


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