For humans to grow and to replace and heal damaged tissues, the body's cells must continually reproduce, a process known as "cell division," by which one cell becomes two, two become four, and so on. A key question of biomedical research is how chromosomes, which are duplicated during cell division so that each daughter cell receives an exact copy of a person's genome, are arranged during this process.
Now, scientists at the Salk Institute have discovered a new characteristic of human cell division that may help explain how our DNA is organized in the nucleus as cells reproduce. They found that telomeres, molecular caps that protect the ends of the chromosomes, move to the outer edge of the cell's nucleus after they have been duplicated.
While the implications of this spatial reorganization of telomeres are not yet clear, the findings may shed light on how our genes are regulated and how gene expression programs are altered during cell division, an important step in understanding aging and diseases that stem from genetic mutations, such as cancer.
"What we discovered is that telomeres not only protect our chromosomes, they also help organize our genetic material in the nucleus," says Jan Karlseder, a professor in Salk's Molecular and Cell Biology Laboratory and the Donald and Darlene Shiley Chair. "This is important, because the three-dimensional position of DNA in the nucleus influences gene expression profiles and how the genome morphs over time."
Telomeres, a combination of proteins and DNA, are crucial in DNA replication, tumor suppression and aging. Every time a primary human cell divides, its telomeres get shorter, until critically short telomeres lead cells to self-destruct. Much of Karlseder's research has focused on understanding telomere dynamics in order to develop ways to influence the aging process, and as a result, restrict cancer cell growth.
In addition to exploring the involvement of telomeres in premature aging diseases and interactions between the DNA damage machinery and telomeres, Karlseder studies the role of telomeres during the cell cycle. Previous studies on human cells have shown that telomeres change positions during cell division, suggesting they might also play a role in organizing DNA in the nucleus. But these studies provided only isolated snapshots of telomeres at various stages of the cell cycle.
In their new study, the Salk researchers used advanced time-lapse live-cell confocal microscopy to track telomere movement in real time throughout the cell cycle. They followed the telomeres for 20 hours in living cells by labeling them with molecules that glowed under the microscope. They also recorded the movement of chromatin, a combination of DNA and proteins that forms chromosomes.
The scientists found that the telomeres moved to the outer periphery of the nuclear envelope of each daughter cell nucleus as they assemble after mitosis, the stage of cell division during which the cell's DNA is duplicated to provide each daughter cell with its own copy. By exploring the underlying molecular pathways, the researchers determined that interactions between two proteins, RAP1 and Sun1, seem to tether the telomeres to the nuclear envelope. Sun1 alone was also capable of attracting the telomeres to the nuclear envelope, suggesting the protein is essential for the process and that other elements might be able to replace RAP1 during tethering.
"The tethering of telomeres to the nuclear envelope may serve as an anchor point to reorganize chromatin after each cell division, so that our DNA is correctly situated for gene expression," Karlseder says. "This tethering could also play a role in the maintenance of telomeres, thereby influencing aging, cancer development and other disorders associated with DNA damage. We plan to explore these possibilities in future experiments."
Salk Institute: http://www.salk.edu
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In the article on the discovery of dinosaurs (They’re back, Review, 6 June) you state: “In Sussex, a local doctor uncovered fragmentary remains of what appeared to be two more species of colossal extinct land reptiles.” You grossly underplay the contribution of Lewes-born Gideon Mantell, geologist and palaeontologist, author and diarist, friend to princes and international scholars as well as local doctor. Mantell not only discovered (aided by his wife) the first remains of the iguanodon in 1824 but named it – as it resembled the tooth of an iguana. This was the first known land dinosaur, Mary Anning having identified the first sea-living dinosaur.Mantell went on to put together more pieces of the jigsaw with extra fossil discoveries. In contrast to Richard Owen, whose models form the basis for the Crystal Palace dinosaurs, Mantell stated correctly that iguanodon would have walked on their back legs, using their forearms to fight or gather food. He did, however, attribute the thumb spike to a nose horn though later corrected this assumption. The Natural History Museum has a display on Gideon and his wife Mary’s contribution as well as the large “Mantell-piece” of Iguanodon fossils that he had on show in his museum in Brighton. He sold it, along with many more priceless items, to the British Museum in 1838. Gideon Mantell’s reputation deserves better than your throwaway remark. Debby MatthewsLewes, East Sussex Continue reading...
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