2015 Nobel Prize in Chemistry Awarded for Research on DNA Repair Mechanisms

2015 Nobel Prize in Chemistry Awarded for Research on DNA Repair Mechanisms

By Siwei Zhang

After spending a whole week of holiday on the sunny beach of the Mediterranean Sea, Sarah finally had all her luggage packed and flew back to the gloomy, rainy Manchester in Lancashire, England. Needless to say, Sarah, as most of her Anglo-Saxon friends, is now glowing as red as a lobster after her week-long bath under the Mediterranean Sun. But she is confident that the red blush will fade away within the next two weeks or so, just as it has been doing for the previous twenty years of her life. However, it was not until the mid-1970s that such mechanisms of tissue repair – altogether with the concept of radiation-caused skin cancer, were fully understood by the work of the three Nobel Laureates in chemistry this year. From the production of high-fidelity PCR enzymes to increased public awareness of sunburn and skin cancer, their research opened a whole new field with the focus on the mechanism of DNA repair.

Roughly, ten years after the DNA double helix and semi-conservative replication theories were discovered, the common concept within the field of science was that DNA itself is a pretty robust and stable molecule, mostly due to its unique and sturdy base-pairing property. However, it was the Swedish scientist Tomas Lindahl that, during his postdoctoral times at Princeton and Rockefeller, revealed that DNA is subject to a considerable rate of decay and, if there was not another repair mechanism present to counterbalance this trend, our genetic materials would soon end up in no more than a roll of messy strands within just a few cell cycles. It is his theory that inspired the fellow researchers, Paul L. Modrich at Duke University and Aziz Sancar at UNC Chapel Hill, who eventually found the enzymes responsible for excision and incision-based DNA repair mechanism. The three scientists shared the 2015 Nobel Prize in Chemistry for their “mechanistic studies of DNA repair”.

The revelation of such important repairing mechanisms presented an extensive impact on almost every niche of cell biology and biochemistry. On the molecular scale, scientists and biotechnology companies can design and manufacture PCR polymerases that possess the “proofreading” ability, which increases the reliability of PCR reactions more than 1000 times in comparison to the non-proofreading ones. For the general consumer markets, the concept of ultraviolet-induced DNA damage and repair greatly enhanced public awareness on the potential danger of sunburn and associated skin cancer risks, which in turn boosted the research and marketing of a full line of sunscreen-related products. For diagnostic and medical practices, inherited deficiencies of particular DNA repair-related genes have been considered as risk factors for potential cancer patients as well as accelerated aging and, as a result, modern molecular diagnostic and treatment methods have been developed accordingly.

Although the discoveries were made more than 40 years ago, only recently has it begun to provide opportunities for biotechnological and biopharmaceutical industries. The widely reported Angelina Jolie and her BRCA1 gene deficient story only marked the very beginning of a new age of DNA repair-related cancer prevention, diagnosis, and treatment. With more than 20 genes being attributed to increased cancer risks and more than 10 aging-related diseases having their source genes pinned down, we are expecting a full blossom of anti-cancer and anti-aging research and development in the coming years.

Image courtesy of pixabay.com

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