Nobel Prize in Chemistry 2015: DNA Repairing Mechanisms that Keep you Alive

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DNA repair mechanisms are crucial to our existence. Without them, we would not survive because of DNA damage caused by the environment (e.g UV light damage, radiation etc.). This crucial research into discovery of three DNA repair mechanisms was led by Thomas Lindahl, Paul Modrich and Aziz Sancar who jointly received this years Nobel Prize in Chemistry (by the way, what is up with the Nobel Foundation‘s categories? Why is a DNA repair mechanism categorised in Chemistry?).

Dr. Francis Crick's Nobel Prize Medal on Heritage Auctions

The Nice Medal with Alfred Nobel’s portrait

Even if CRISPR was in the short-list to win the prize, this trio’s DNA repairing mechanisms were awarded the Nobel prize in Chemistry (which if we’re honest at Labiotech, did not see coming at all…).

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Arguably, one possible reason for this is that Lindahl & co.’s discovery is over 30 years old, whilst the gene-editing system CRISPR/Cas9 was only published in 2012. CRISPR is currently occupied in an intense patent war, which may end soon with the discovery of a replacement protein to Cas9, and it’s not entirely clear who is the real inventor of the technology (as Wired reported extremely well here). CRISPR will therefore probably have to wait one (or several) years before their discovery is considered ‘seasoned’ enough to join the Nobel elite.

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Credit: Johan Jarnestad/The Royal Swedish Academy of Science


Back to this year’s winners…

It all started in the early 1970s with Tomas Lindahl, a Swedish research doctorate who holds a PhD from the Karolinska Institute and who also formerly conducted research at the Francis Crick Institute (UK). Not that we’re bitter for CRISPR or anything, but we wonder if this small detail could have helped them win the prize (seeing as the awarding institution is also the Karolinska)..?

Lindahl showed that whilst people believed DNA was ultra-stable, the helical molecule is actually facing high rates of degradation all the time in a continual battle against destruction. To explain better, the molecule is in fact fairly robust against such molecular failure, but exists in a constant state of damage and repair. This discovery led him to also find the specific base excision repair mechanism responsible for counteracting the collapse of our DNA.

Basic Excision Repair

Base Excision Repair (Credit: Johan Jarnestad/The Royal Swedish Academy of Science)

Further down the DNA timeline, Aziz Sancar demonstrated how cells uses the Nucleotide excision repair mechanism to repair UV damage to DNA, proving that people with defects in these mechanisms had a higher risk of developing skin cancers when over-exposed to sunlight (it’s basically because of him that you have to slather on suncream every 2 hours at the beach).

Finally, the 3rd Nobel winner for Chemistry is Paul Modrich, who highlighted the DNA repairing mechanism during cell division. It’s called ‘mismatch repair‘, and it corrects the error frequency during DNA replication by a thousandfold, thus enabling our cells to replicate identically.

Deregulation of these mechanisms is one of the main causes of cancer today, and explains how our body has survived the thousands of modifications our genomes undergo daily, which during cell-division can number in the millions.

Credit: Nature Publishing Group Hoeijmakers, J. H. J. Genome maintenance mechanisms for preventing cancer. Nature 411, 366–374 (2001)

Credit: Nature Publishing Group Hoeijmakers, J. H. J. Genome maintenance mechanisms for preventing cancer. Nature 411, 366–374 (2001)

Beside the fundamental discovery, the understanding of these natural DNA repair mechanisms is what has really had a tremendous impact on our daily lives;  i.e. the fight against cancer (through new therapies against cell repairing deregulation), to develop novel gene therapies for people born with dysfunctions, and even helping produce new biofuels due to exploitation of Bacteria with powerful DNA repairing mechanism (such as Deinococus to achieve higher yields).

Repairing DNA is therefore crucial to the human species and many species around the globe, and that’s why the three pioneering scientists received this Nobel Prize (and the associated €1M).

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