NEW YORK, July 24, 2008 In the life of a cell, the response to DNA damage determines whether the cell is fated to pause and repair itself, commit suicide, or grow uncontrollably, a route leading to cancer. In a new study, published in the July 25th issue of Cell, scientists at NYU Langone Medical Center have identified a way that cells respond to DNA damage through a process that targets proteins for disposal. The finding points to a new pathway for the development of cancer and suggests a new way of sensitizing cancer cells to treatment.
"One of the major messages of this study is that we have a new pathway that responds to DNA damage," says Michele Pagano, M.D., the May Ellen and Gerald Jay Ritter Professor of Oncology and Professor of Pathology at NYU School of Medicine, who was recently appointed a Howard Hughes Medical Institute Investigator. "It is already known that the three major protein players in this pathway are deregulated in human cancers, so deregulation of this pathway is probably going to contribute to tumorigenesis (the development of cancer)."
DNA damage can be caused by carcinogens in the environment, errors in DNA replication, or glitches in the cellular machinery caused by aging, among other factors. If a cell detects DNA damage when it is about to divide, it activates the so-called G2 checkpoint, a pause button that allows the cell time to correct the problem before cell division, the process whereby a cell makes two copies of itself. The cell maintains a paused state based on a series of proteins, a pathway, that work together like gears in a machine. Some are switched on and others are turned off (often by degradation) to maintain the checkpoint.
In addition to the new pathway's association with cancer, it suggests a potentially new way to sensitize cells to chemotherapy, says Dr. Pagano. Tumor cells already have a less efficient checkpoint because of defects in other regulatory pa
|Contact: Jennifer Berman|
NYU Langone Medical Center / New York University School of Medicine