Biomedical Frontiers: Fall 1997, Vol.4, No.2
A Radiation Gene

Chromosomal location of HRAD 9.

A newly identified human gene may help protect against damage from radiation exposure.

In a study published in the Nov. 22, 1996, issue of Proceedings of the National Academy of Sciences, researchers from CPMC, Queen's University (in Ontario), and the University of Calgary identified the gene HRAD 9, a human homolog of the fission yeast gene rad9. In fission yeast with mutant rad9, HRAD 9 was able to rescue the gene function.

Fission yeast (Schizosaccharomyces pombe) has been used for years as a model for studying mechanisms of radiation and drug resistance, says Dr. Howard Lieberman, lead author and associate professor of clinical radiation oncology at Columbia. Fission yeast cells with mutant copies of rad9 are very sensitive to the deleterious effects of radiation, dying at low doses. "It's likely that HRAD 9 also plays an important role in how human cells respond to radiation exposure," says Dr. Lieberman.

So far, indications are that both HRAD 9 and rad9 are involved in the cell cycle checkpoint, with evidence pointing to the G2/M checkpoint, at least for rad9. "When normal cells are irradiated, the checkpoint mechanism stops cell division until the damage is repaired," says Dr. Lieberman. "In rad9 mutants, there is no checkpoint, so the cells continue to divide even though their DNA is damaged."

The finding has important implications for radiation therapy. For instance, individuals with mutant copies of HRAD 9 might be more likely to suffer adverse effects of radiotherapy years after treatment. Genetic screening could ensure that these individuals are given alternative treatments. Conversely, those with normal copies of HRAD 9 might be able to withstand higher and more effective doses of radiation.

Dr. Lieberman's work on HRAD 9 is funded by grants from the National Institutes of Health and the Department of Energy.

S. pombe cells containing a normal rad9 gene accumulate in the late G2 phase of the cell cycle transiently after exposure to radiation and appear elongated. Cells containing the mutant form of rad9, rad9-192, do not delay cycling post-irradiation. The lack of this type of checkpoint function in mammals may be linked to cancer.