The Royal Swedish Academy of Sciences has awarded this year’s Nobel Prize in chemistry to three scientists for their extensive work on how cells repair damaged DNA. Their discoveries are helping guide the development of breakthrough cancer treatments. Researchers are now developing drugs that target molecular pathways used by cancer cells to proliferate.
Lindahl’s journey to Nobel Prize began decades ago
The Nobel Prize in chemistry was shared by Tomas Lindahl of Sweden, Aziz Sancar of Turkey, and Paul Modrich of the United States. Notably, the three scientists had conducted their research independently of each other, but were awarded the Noble Prize together for “mechanistic studies of DNA repair”. The Royal Swedish Academy of Sciences said their work provides fundamental knowledge of how a living cell functions, which is helpful in the development of new cancer drugs.
For decades, scientists believed that DNA was highly stable. But in the 1970s, Dr. Lindahl of Clare Hall Laboratory in the UK discovered that DNA undergoes thousands of alterations every day due to spontaneous changes and devastating effects of free radicals, radiation, and carcinogenic substances like cigarette smoke. Despite all this, a cell’s genome remains intact. So, how does the DNA remains in good condition?
Dr. Lindahl later identified a bacterial enzyme that is part of a cell’s toolbox for DNA repair. He published findings of his study in 1974. In the following years, he discovered numerous proteins that help a cell in DNA repair.
Dr. Modrich demonstrated the ‘mismatch repair’ mechanism
Separately, Dr. Aziz Sancar, a professor of biochemistry at the University of North Carolina, successfully mapped a process called “nucleotide excision repair,” that allows cells to repair DNA molecules damaged by UV rays. Those who inherit defects in this repair mechanism are highly likely to develop skin cancer when exposed to sunlight.
Dr. Modrich of Duke University School of Medicine in Durham, NC, has successfully demonstrated how cells use the “mismatch repair” mechanism to fix errors that occur during DNA replication in the process of cell division.
We need to understand the mechanism of DNA repair to selectively provide good cancer therapy. Sometimes a treatment given to a patient to kill cancer cells isn’t effective because the tumor cells fight back with DNA repair. If researchers can figure out how to disable the DNA repair mechanism of cancer cells, it would lead to more effective treatments.