DNA damage resets the circadian clock in mammals, researchers report in this week's online issue of Current Biology.

Previous studies have shown that DNA damage affects circadian cycles in the fungus Neospora. Here, Malgorzata Oklejewicz at Erasmus University Medical Center in the Netherlands and colleagues demonstrated the effect not only in mammalian cell lines, but also in mice in vivo. "This interaction between DNA damage response and the circadian clock is preserved through evolution," said Roman Kondratov, a cancer biologist at the Cleveland State University, who was not involved in the study.

The researchers treated mammalian cells with a number of DNA-damaging agents: ionizing radiation, ultraviolet light and a chemical compound that causes oxidation, and looked at the subsequent expression of mPER2, a key circadian clock gene. They saw that the amount that the clock shifted forward, as indicated by a shift in gene expression, depended on the dose of radiation. They also found that ATM kinase, which is known to initiate DNA repair, was responsible for communicating DNA damage to the clock machinery. The clock shift also had behavioral effects: Mice treated with non-lethal irradiation moved their activity cycles forward.

Earlier research has shown that circadian cycles can affect a cell's response to DNA damage, which has implications for the time of day patients are treated with chemotherapy or radiation, said Kondratov. The new study suggests that the relationship between DNA damage and the circadian clock may go both ways, and could provide an explanation for side-effects of cancer therapies. As to whether the findings will affect cancer treatment, Kondratov said, it's too early to tell. "We still don't know how big the effect will be in humans."