DNA repair linked to circadian clock, leading to optimized therapy: study

Updated 2018-05-08 10:47:04 Xinhua

American Scientists found that the DNA repair varied with the circadian clock, opening up new possibilities for chronotherapy.

A study published on Monday in the Proceedings of the National Academy of Sciences revealed that DNA repair of normal tissue was most robust predawn and pre-dusk in mice.

The team of Aziz Sancar, a professor of biochemistry and biophysics from the University of North Carolina School of Medicine and the study's senior author, developed a way to measure the repair of DNA damage caused by cisplatin, a common anti-cancer drug but toxic to kidneys, liver and nervous system.

Sancar's lab measured DNA repair after cisplatin treatment over the course of an entire 24-hour circadian cycle throughout an entire genome of a mammal.

"We found there are close to 2,000 genes, different parts of which are repaired at different times of day, depending on the gene," said Sancar.

In the study, they described how DNA repair after cisplatin treatment affected different parts of these genes, parts involved in transcription and parts that weren't involved.

During transcription, part of the double-helix DNA molecule creates a single-stranded RNA molecule that will either serve a crucial biological function in a cell or undergo an additional step to produce a protein, which will serve an important cellular function.

They found that the repair processes of transcribed strands tended to peak at predawn or pre-dusk, depending on the gene, while repair of the non-transcribed strand tended to peak only at pre-dusk.

Knowing how and when normal cells in various organs undergo DNA repair would help doctors understand the best times to administer drugs. For instance, cisplatin interferes with gene transcription to prevent cell division and growth, potentially leading to cancer cell death.

"Our work suggests it could be best to give cisplatin to patients when their normal cell DNA repair is at its zenith," Sancar said.

"Right now, we are still learning the basic mechanisms of DNA repair in relation to the circadian clock. But we think understanding the precise ways our circadian clocks work is key to slowing the progression of cancer. And we think it's possible to harness the power of chemotherapy while decreasing toxic side effects," said Sancar.

Researchers also suggested chronotherapy was important for various conditions, including asthma, epilepsy, and heartburn.

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