CHAPEL HILL - Scientists at the University of North Carolina at Chapel Hill's Lineberger Comprehensive Cancer Center and Rockefeller University appear to have solved an important and long-standing mystery in cell biology. The puzzle is why cells' internal repair machinery doesn't mistake the ends of chromosomes for broken DNA and either "fix" or destroy them.

Working together, the researchers have discovered that mammals' chromosomes end in loops. Under intense magnification, those chromosome ends, or telomeres, look something like lassos.

A report on the findings appears as the cover story in the May 14 issue of the journal Cell. Lead authors are Drs. Jack Griffith, professor of microbiology and immunology at the UNC-CH School of Medicine, and Titia de Lange, professor and head of Rockefeller's Laboratory of Cell Biology and Genetics.

"We think this work is highly important because it should provide a whole new way of thinking about basic molecular mechanisms related to cancer and to control of aging in cells," Griffith said.

Genetic information in cells is stored in 46 long thread-like molecules called DNA, and each is packaged into a rod-shaped structure called a chromosome, he explained. When cells are exposed to X rays or other insults that break DNA molecules, the repair mechanisms stitch the broken ends back together. If too many breaks occur, then a cellular suicide response kicks in, and cells die.

"The question has been why natural chromosome ends, of which there are 92 per cell, do not trigger that response," the scientist said. "We believe we've found the answer."

For the first time, the researchers have produced photographs that show the loops clearly.

"The first clue came from studies by Dr. de Lange's group of one of the proteins they had discovered," said Griffith, whose laboratory employs electron microscopes to investigate the architecture of DNA molecu
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Contact: David Williamson
David_Williamson@unc.edu
919-962-8596
University of North Carolina at Chapel Hill
14-May-1999