Inactivating a protein called mammalian Rad9 could make cancer cells easier to kill with ionizing radiation, according to research at Washington University School of Medicine in St. Louis.
The researchers found that Rad9, previously considered a "watchman" that checks for DNA damage, is actually a "repairman" that fixes dangerous breaks in the DNA double helix. They found Rad9 is especially active in telomeres, the protective ends of chromosomes.
Because of this new role, Rad9 has gained the researchers' interest as a potential target for cancer therapy -- knocking out Rad9 would enhance the power of radiation treatments by making it easier for radiation to inflict fatal damage to a tumor's genetic material. Their study appears in the March issue of the journal Molecular and Cellular Biology, which is now available online.
"Our study suggests that if we could inactivate Rad9 in tumor cells, we would be able to kill them with a very low dose of radiation and gain a therapeutic advantage," says senior author Tej K. Pandita, Ph.D., associate professor of radiation oncology and on the faculty of the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.
The study revealed that Rad9 proteins interact with chromosomes' telomeres, which are special structures at the ends of chromosomes that protect them from fusion or degradation. Specifically, Rad9 proteins were shown to interact with proteins called telomere binding proteins. When the scientists inactivated Rad9 in human cells, they saw damage to chromosomes and end-to-end fusion at telomeres. DNA damage and chromosomal fusion can disrupt the cell cycle and cause cell death. Because radiation treatments increase these incidents, loss of Rad9 in cancer cells could enhance the killing effect of radiation.