Chromosome "anchors" organize DNA during cell division
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 in 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 Salk scientists 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.
"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 the Molecular and Cell Biology Laboratory and holder of 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."
Previous studies on human cells have shown that telomeres change position during cell division, suggesting they might 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, Karlseder and his team used advanced time-lapse live-cell confocal microscopy to track telomere movement in real time throughout the cell cycle. They also recorded the movement of chromatin, a combination of DNA and proteins that forms chromosomes.
The scientists found that the telomeres move to the 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.
"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."