Researchers at Los Alamos and Lawrence Berkeley national laboratories and the Memorial Sloan-Kettering Cancer Center in New York City have made surprising new discoveries about a connection between DNA repair proteins and normal maintenance activity occurring at chromosome tips called telomeres. The findings may one day lead to new paths in cancer research.

Telomeres are known to have important roles in cancer development and in the aging process. LANL provided the first detailed information on the sequence and importance of human telomeres and centromeres (constricted chromosomal regions) in cell division.

In this study, researchers found that the presence of the repair protein DNA-dependent protein kinase (DNA-PK), which is typically found around broken DNA ends, plays a key role in preventing normal chromosomes from fusing together end to end. Such fusions cause cellular instability and can lead to cancer. In earlier studies involving yeast chromosomes, other research groups discovered that DNA repair proteins are associated with normal telomere maintenance.

"Through some unknown mechanism, the repair proteins allow a cell to recognize telomeres as natural ends and not broken DNA strands in need of repair," observed LANL team member Susan Bailey. "Understanding this mechanism could lead us into completely new directions in cancer research, perhaps even in gene therapy," she concluded. Results of the study were published in the December 1999 issue of the Proceedings of the National Academy of Sciences.

Funding for the research was provided by grants from DOE, the U.S. Army, and NIH.

 

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