CU Cancer Center researchers figure out how cells know they are repaired
Breakthrough published in July 25 edition of Cell
Jessica Tyler, PhD
AURORA, COLO. (July 29, 2008)—Researchers at the University of Colorado Cancer Center have identified the key marker cells use to know when broken DNA has been repaired and it is safe for the cell to begin dividing again.
Jessica Tyler, PhD , leader of the University of Colorado Cancer Center’s Molecular Oncology Program and assistant professor of Biochemistry and Chemistry at the University of Colorado Denver, and her group have an article in the July 25 edition of Cell that discusses a breakthrough in understanding the basic mechanisms of cell cycle regulation.
In 2001, Lee Hartwell, PhD, won the Nobel Prize in physiology or medicine for his discovery of "checkpoint" genes that determine whether a cell is dividing normally. These checkpoints act as brakes that stop a cell with damaged DNA from dividing. The checkpoint is turned on, and normal cells mobilize mechanisms to fix that break on the DNA. When the DNA repair is finished, the checkpoint is turned off and the cell can divide again.
Dr. Tyler's group has identified how the cell knows to turn off the checkpoint.
"When the checkpoint is activated, chromosomal proteins—specifically histones—are removed from the DNA," she explains. "You then have naked DNA. The DNA break is repaired. Then the histones are put back onto the DNA. We've discovered the mechanism that takes care of that last bit. We have also proven that the act of putting the histones back on the DNA tells the cell it is safe to divide again, not the physical act of DNA repair."
The process involves a change in the epigenetic information carried by the histones via acetylation, which tells histones to go back onto the DNA and turn off the cell checkpoint. Dr. Tyler and her group in 2006 solved the structure of a complex of a key protein required for this histone acetylation bound to histones, in collaboration with Mair Churchill, PhD, of the UC Denver Department of Pharmacology (also published in Cell).
"Many cancer cells have mutations that turn off this braking mechanism," Dr. Tyler says. "We believe the proteins that make this epigenetic mark could be a new target for cancer therapy."
About the University of Colorado Cancer Center
The University of Colorado Cancer Center is the Rocky Mountain region’s only National Cancer Institute-designated comprehensive cancer center. NCI has given only 40 cancer centers this designation, deeming membership as “the best of the best.” Headquartered on the University of Colorado Denver Anschutz Medical Campus, UCCC is a consortium of three state universities (Colorado State University , University of Colorado at Boulder and University of Colorado Denver) and six institutions (AMC Cancer Research Center , The Children’s Hospital, Denver Health, Denver VA Medical Center, National Jewish Health and University of Colorado Hospital). Together, our 400+ members are working to ease the cancer burden through cancer care, research, education and prevention and control. Learn more at www.uccc.info.