A Mayo Clinic-led research collaboration has discovered that the protein MDC1 amplifies weak DNA injury signals so genetic repair can begin.
Once amplified, even low-level damage signals become strong enough to activate the cell's natural repair processes while the injury is most tractable to repair.
How this "distress call" was communicated wasn't clear until this finding, which appears in the January 20 issue of Molecular Cell. The research was conducted in collaboration with colleagues from Harvard University and the University of Texas, Austin.
"It's important that DNA lesions get repaired because then we don't get mutations," says Junjie Chen, Ph.D., Mayo Clinic oncology researcher and leader of the Mayo Clinic team. "This is just one mechanism involved in communicating injury to the repair processes, but it's an important start to understanding how we might one day design new treatments that help this repair system recover from injury or resist injury."
Dysfunction of the DNA damage response pathway makes the gene unstable. Genomic instability is the driving force in tumor formation, which is why cancer researchers around the world are focusing on understanding the DNA damage response pathway. Knowing how the cell communicates DNA injury to alert the repair system is an important first step to designing new therapies for cancers and other diseases.
The damage control process is continual and essential to health. DNA must repair itself so the instructions it gives to operate bodily functions are correct. In earlier work, the Mayo Clinic researchers determined that MDC1 is important to the repair process -- but they didn't know its role.
DNA is easily and often damaged by environmental and chemical sources such as ultraviolet radiation, cigarette smoke, and other natural and artificial toxins. These create injury sites or lesions. In healthy situations, DNA repair signal pathways are competently monitoring for damage and alerting the repair system when DNA lesions are detected.