Synthetic DNA Nanocircles Aid Study of Aging in Cells

Nanotechnology researchers have created synthetic DNA nanocircles, which they say can act as essentially infinite catalytic templates for efficient synthesis of long telomeres by DNA polymerase enzymes. Their work was reported November 20, 2002, in the online edition of the Proceedings of the National Academy of Sciences.

Telomeres are the physical ends of linear eukaryotic chromosomes. They are specialized nucleoprotein complexes that have important functions, primarily in the protection, replication, and stabilization of the chromosome ends. In most organisms studied, telomeres contain lengthy stretches of tandemly repeated simple DNA sequences composed of a G-rich strand and a C-rich strand (called terminal repeats). These terminal repeats are highly conserved, and in fact all vertebrates appear to have the same simple sequence repeat in telomeres (TTAGGG)n. Often sequences adjacent to the telomeric repeats are highly polymorphic, are rich in DNA repetitive elements (termed subtelomeric repeats), and in some cases, genes have been found in the proterminal regions of chromosomes.

The synthetic DNA nanocircles developed by researchers at Stanford University (Stanford, CA, USA; www.stanford.edu) mimicked the function of the telomerase enzyme that normally adds new TTAGGG sequences to the end of the telomere.

"Nanocircles are so simple they are amazing,” observed Dr. Eric T. Kool, professor of chemistry at Stanford. "Each nanocircle acts like a template that says, ‘Copy more of that sequence.' In the test tube, we start with very short telomeres and end up with long ones that are easy to see under the microscope with fluorescent labeling. This suggests the possibility that one day we may be able to make cells live indefinitely and divide indefinitely, so they essentially become refreshed, as if they were younger.”

Since researchers need to study cells that live a long time, many laboratories rely on tumor-derived cells, which continuously divide. Dr. Kool predicted that nanocircle technology could one day provide an alternative method that would allow researchers to use healthy cells in their experiments instead of cancerous ones. "Maybe we would not need stem cells,” he said. "We would not need to get into the controversy of where stem cells come from if we could just take normal cells and grow them.”



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