In experiments with yeast cells, the scientists discovered that if the two controller proteins remain in the cell then copying continues abnormally. Normally, the proteins are destroyed after a single copy, or replication, of the DNA is made.

"We knew these proteins were required for DNA replication and that they normally went away after one DNA copy was made, but we didn't know whether their disappearance was important for controlling the duplication of the genome," says Thomas Kelly, M.D., Ph.D., professor and director of molecular biology and genetics and director of the Institute for Basic Biomedical Sciences. "Now we know that DNA replication ceases because these two proteins are destroyed."

Understanding this complex and tightly regulated process may help clarify what goes wrong in cancer cells, say the researchers. The yeast used in the experiment (Schizosaccharomyces pombe) divides by splitting into two new cells, each with a copy of the organism's entire genome, in a process very similar to that of human cells.

"In human cells, for reasons still largely unknown, some cells ultimately acquire enough genetic mutations to cause cancer, despite having different ways to prevent, find and fix problems in the genome," says Mark Frattini, M.D., Ph.D., a postdoctoral fellow in the department of medical oncology and the department of molecular biology and genetics, which is part of the school's Institute for Basic Biomedical Sciences. "We can't yet link these two controller proteins in yeast or their human counterparts to cancer, but we do have a new genome control pathway to examine."

In the yeast, one controller, the Cdc18 protein, helps build mac
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Contact: Joanna Downer
jdowner1@jhmi.edu
410-614-5105
Johns Hopkins Medical Institutions
22-Oct-2001