A tiny, protein-operated clock inside our cells that operate based on the 24-hour day cycle. These circadian clocks are important for the proper biological function of different organs – heart, liver, lungs, brain, skin. Yet, we don't know exactly how they interact with other basic and crucial biology, such as DNA repair – the process our cells constantly undergo because we are perpetually bombarded with stuff that wrecks DNA. The study was published in the Proceedings of the National Academy of Sciences.
The UNC School of Medicine lab of Nobel laureate Aziz Sancar, MD, Ph.D., works on these two fronts of the circadian clock and DNA repair. Sancar's lab developed a way to measure the repair of DNA damage caused by cisplatin, a common anti-cancer drug. And for the first time, his lab measured DNA repair after cisplatin treatment over the course of an entire 24-hour circadian cycle throughout an entire genome of a mammal.
The researchers found what sites in the genome were repaired, what specific genes were repaired, and when. They found that DNA repair of normal tissue was most robust predawn and pre-dusk in mice. They believe understanding these circadian patterns and kinetics throughout the genome and in various organs will help us discover and develop better treatment regimens for people with cancer.
Researchers are trying to develop cisplatin derivatives with less toxicity. Another approach is chronotherapy administering treatments according to our biological clocks. Research suggests chronotherapy is important for various conditions, including asthma, epilepsy, and heartburn. A study showing DNA repaired after damage.
Their work on the nucleotide excision repair system helps explain why we don't all get skin cancer even though ultraviolet radiation is constantly damaging our DNA. This repair system and others are the reasons our cells stay healthy even while exposed to carcinogens. Nucleotide excision repair is profoundly important and holds clues for creating ways to repair damage due to cancer, to kill cancer without killing healthy cells, and to optimize existing therapies.
They are still learning the basic mechanisms of DNA repair about the circadian clock. But they 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.
To discover how the circadian clock and DNA repair interact, they treated mice with cisplatin over a 24-hour period and used a method they developed over several years to measure the repair of DNA damage throughout the genome of a mouse.
They describe 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.