A process that limits the number of times a cell divides works much differently than had been thought, opening the door to potential new anticancer therapies, researchers at UT Southwestern Medical Center report in the Aug. 7 issue of the journal Cell.
Most cells in the human body divide only a certain number of times, via a countdown mechanism that stops them. When the controlling process goes wrong, the cells divide indefinitely, contributing to cancer growth.
The number of times a cell divides is determined by special segments of DNA called telomeres, which are located at the ends of each chromosome. Every time a cell divides, the telomeres get shorter. When they are reduced to a certain length, the cell stops dividing.
In the new study, UT Southwestern researchers used both normal and cancerous human cells to examine closely how telomeres behave during cell division.
As a cell prepares to divide into two new cells, its ladder-shaped DNA "unzips," creating two halves, each resembling a single upright of a ladder with a set of half-length rungs. Fresh genetic material then fills in the rungs and a second upright. This process creates two identical sets of chromosomes that will be allotted between the two cells.
From earlier studies on model organisms such as yeast, scientists thought that all telomeres replicated late in the stage of overall DNA replication, and by the same processes. The new study suggests that telomeres replicate at various times during this stage, except for a final step that is not completed until the very end, via a different, unknown mechanism.
"Interfering with replication of telomeres might provide a way to halt uncontrolled spread of cancer cells," said Dr. Woodring Wright, professor of cell biology at UT Southwestern and co-senior author of the paper.
The researchers also examined an enzyme called telomerase, which "rebuilds" telomeres so they do not get shorter and signals the cell to stop dividing. Normally, telomerase is only active in cells such as stem cells and dividing immune cells, which must reproduce constantly.