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Scientists Make Key Finding Underlying Genetic Stability

Date:
October 5, 2001
Source:
Los Alamos National Laboratory
Summary:
Biologists at the U.S. Department of Energy's Los Alamos National Laboratory have discovered new insights into how two common proteins found in mammalian cells can cause chromosomes to fuse together -mutations that can destroy cells or give rise to cancer.
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LOS ALAMOS, N.M., Oct. 4 2001 - Biologists at the U.S. Department of Energy's Los Alamos National Laboratory have discovered new insights into how two common proteins found in mammalian cells can cause chromosomes to fuse together -mutations that can destroy cells or give rise to cancer.

The research, by Susan Bailey and Edwin Goodwin of Los Alamos' Biosciences Division, was published recently in the journal Science.

Bailey, Goodwin and their colleagues looked at the role of telomeres in protecting chromosome ends. Chromosomes are made of deoxyribonucleic acid - DNA - and are the carriers of genetic information. Human cells contain 22 pairs of chromosomes plus two gender chromosomes. Telomeres are specialized protective structures at the end of each arm of the X-shaped chromosomes.

Without telomeres, natural chromosome ends appear to the cell like broken DNA ends in need of repair. Mutations in certain genes impair the protective function of telomeres leading to inappropriate "repair," in effect causing chromosomes to fuse together end to end. Chromosome end fusions destabilize the orderly transmission of genetic information to the next generation of cells. The Los Alamos researchers studied telomere dysfunction in order to learn more about how a normal telomere works.

Each chromosome has four telomeres. Mammalian telomeres contain a unique DNA sequence, discovered earlier by Los Alamos' Human Genome Project, as well as specialized proteins that together create a protective cap at the ends of chromosome arms.

Bailey and Goodwin looked at the role of two proteins in telomere function. One protein was known to play a role in telomere function and chromosome end capping. The other protein originally was shown to help repair damaged DNA, but later was shown by Bailey and Goodwin to also help protect natural chromosome ends.

The researchers used human cells provided by Titia DeLange of Rockefeller University that contained artificially induced changes to the first protein and mouse cells with mutations in the second protein. Under normal circumstances, when cells divide they produce exact duplicates, including exact duplicates of the chromosomes they contain. Bailey, Goodwin and their colleagues found that the progeny of cells containing the altered proteins often contained chromosomes that had fused with other chromosomes at one arm. The fused chromosomes had a sausage-like appearance and were easy to distinguish from normal chromosomes. Due to their genetic abnormalities, the damaged daughter cells often were unable to thrive.

The fusing chromosome arms in the dying daughter cells indicated that the malfunction might be associated with telomere replication and indicative that the protein changes induced in the original cells played a role. But Bailey and Goodwin noticed something else - something extraordinary and unexpected.

Using a Los Alamos-developed technique called chromosome-orientation fluorescence in situ hybridization - CO-FISH -that highlights which half strand of the DNA double helix underwent replication during the cell-division process, the researchers determined that the fusion only occurred on specific arms of the chromosomes. What's more, Bailey and Goodwin noticed that fusion never occurred in a chromosome on two arms on the same-side of the "X"; if more than one fusion


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Los Alamos National Laboratory. "Scientists Make Key Finding Underlying Genetic Stability." ScienceDaily. ScienceDaily, 5 October 2001. <www.sciencedaily.com/releases/2001/10/011005065212.htm>.
Los Alamos National Laboratory. (2001, October 5). Scientists Make Key Finding Underlying Genetic Stability. ScienceDaily. Retrieved April 17, 2024 from www.sciencedaily.com/releases/2001/10/011005065212.htm
Los Alamos National Laboratory. "Scientists Make Key Finding Underlying Genetic Stability." ScienceDaily. www.sciencedaily.com/releases/2001/10/011005065212.htm (accessed April 17, 2024).

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