Telomere Repair, Well-Timed

Self-correcting. Telomeres (red) within cloned embryos are automatically elongated.

The loss of chromosome-protective telomeres has been considered a major barrier to the creation of healthy mammal clones, but scientists have been unable to determine how telomere length is controlled in developing embryos. Research on mouse and cow clones, reported in the 17 May issue of the Proceedings of the National Academy of Sciences, sheds light on how some clones deal with this problem.

The ends of chromosomes are capped by wads of DNA called telomeres. Each time a cell divides, they get clipped a little bit shorter. When the telomeres are worn away, the chromosomes become vulnerable to mutations, possibly paving the way for age-related diseases such as atherosclerosis and certain cancers.

As a safeguard, in cells such as egg, sperm, and stem cells, an enzyme called telomerase is responsible for preventing this wear and tear by maintaining telomere length. But after development is finished, telomerase becomes inactive in adult cells. One of the expected dangers of cloning is that worn down telomeres will be inherited from the adult cells used in lieu of an egg or sperm cell, and indeed the telomeres of adult clones are often shorter than normal.

To see what might go wrong with the telomeres of cloned animals between cell fusion and maturity, a team led by Lenhard Rudolph of the Hannover School of Medicine and Heiner Niemann of the Institute for Animal Science at Mariensee, Germany, tracked the length of telomeres during development. By comparing mouse and cow embryos made either by normal fertilization, in vitro fertilization, or cloning, they discovered that developing embryos can fix short telomeres.

No matter where the source of their DNA, as soon as the embryos became hollow balls of cells, between the developmental stages known as blastocyst and morula, telomerase lengthened telomeres to the right size. In embryos where the telomerase gene was deleted, the telomeres of all embryos became shorter than normal.

This study reveals the "crucial moment in development" when the telomere deficiency of cloned embryos gets fixed, says Maria Blasco, a molecular biologist at the Spanish National Cancer Center in Madrid, Spain. Why do some clones still end up with short telomeres? Blasco suspects that cloning can lead to chemical modification of DNA, possibly blocking telomerase from its target.

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