ntial role in the cell cycle, Dr. Benezra says. After a cell's DNA is copied, each pair of the duplicated chromosomes is bound together at structures, called centromeres, that fit around each chromosome like a napkin ring. In order for a cell to divide, thread-like fibers must attach to each centromere and pull the chromosomes apart. That's where the MAD2 gene comes in.

The research suggests that MAD2 produces a protein that sits at the centromere of each chromosome and waits for the thread-like fibers to attach. If the fibers attach properly, cell division proceeds and each new cell gets a complete copy of the genetic blueprint of the original cell. But if the fibers fail to anchor to one of the centromeres, the corresponding chromosome pair can't separate normally and MAD2 puts the brakes on cell division.

Dr. Benezra speculates that MAD2 is only one of several genes involved in triggering this cell division checkpoint. In yeast, for example, six genes are known to exert their control over the checkpoint. Dr. Benezra, whose team discovered the MAD2 gene by accident, also is investigating a second human gene suspected of being involved in the checkpoint.

The new research may help to improve future treatment options for cancer patients. In the study, the researchers identified a human breast tumor cell line that is sensitive to the cancer drugs taxol and nocodazole. The drugs, called spindle inhibitors, block the formation of the thread-like fibers that pull chromosomes apart during cell division.

After the researchers treated the breast tumor cell line with nocodazole, the cells continued to undergo cell division, which suggests the cells may be defective in the checkpoint. When the investigators looked further, they confirmed their suspicion -- the cell line had low levels of MAD2 expression compared to control cells that were resistant to both drugs.

The drugs may be especially effective in the treatment of tumors with a defective checkpoint,
'"/>

Contact: Chris Westerman
westermac@mskcc.org
212-639-3576
Memorial Sloan-Kettering Cancer Center
11-Oct-1996

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