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
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
PTSD treatments could soon extend beyond therapy
Areas where Czechoslovakia had three electrified fences now avoided by generation of deer who never encountered them
The mystery of a bizarre quacking sound often heard in the Southern Ocean has finally been solved, scientists report.
Why the connections between brain cells in depressed people are often shrivelled was a mystery – but a single protein could be to blame
The threat of mutually assured destruction, military or economic, promotes peace in many places. If war has ultimately forged a safer world, what's next?
Submarine company says it has recorded detailed images of World War II wrecks off England
Maine baby lobster decline could mean end to record catches as lobstermen, scientists worry
A look at the critters that live on money finds about 3,000 types of bacteria. Most are harmless. But researchers found traces of DNA from anthrax and drug-resistant pathogens, too.
Over its lifetime, Earth has hosted countless species. But some of those species, like the dinosaurs, have managed to claw their way into a special place in our imaginations. Now, a new book illustrates the dinosaurs — and many of the beasts of millennia ago — in beautiful, spectacular and vicious style.
Monkeys have been taught to add, giving the best evidence yet for primates' maths skills and offering a path towards solving how the brain encodes numbers