Undoubtedly, many of you will have heard last week’s announcement that the 2015 Nobel Prize for Chemistry was awarded to Thomas Lindahl, Paul Modrich and Aziz Sancar for their work into “mechanistic studies of DNA repair“. However, for a lot of us, this work is outside of our field of research, so what exactly did these men achieve, and what does it mean?
Firstly, let’s talk about DNA repair. Why is this needed? The DNA in our cells is damaged every single day through a variety of natural and external processes, Natural sources of damage can include attack by reactive metabolic byproducts within the body, or errors in the initial replication of the DNA. Cells can also become damaged by harmful chemicals and toxins, radiation damage, thermal damage or attacks by viruses. When this DNA becomes damaged, cells can’t function correctly, as the information contained within them is now corrupted and inaccessible. It is therefore vital that your body is able to spot damage to DNA and consequently repair it.
Real pioneering work into this began with Thomas Lindahl in the 1960s, when he questioned the apparently stability of DNA. Indeed, he discovered that DNA did undergo degradation, and the idea of DNA repair was born. Lindahl put together the idea of base excision repair (see below), where an enzyme called glycosylase cuts out a mismatched base so that it can be replaced and the DNA can be fixed.
Aziz Sancar worked particularly in the area of repairing UV damage. He put forward the theory of nucleotide excision repair, where a whole section of the DNA strand is removed to get rid of a faulty nucleotide caused by UV damage. DNA polymerase fills in the resulting gap, allowing the DNA to function correctly.
Paul Modrich worked on understanding how the body repairs damages caused during cell division. He devised a mechanism by which the body rectifies mismatched nucleotides formed during cell replication, cuts out this faulty strand, and fills in the gap. This is known as mismatch repair. It’s an amazing phenomenon, and 99.9% of such errors are repaired in this way.
Not only did the outstanding work carried out by these three men develop the understanding of how DNA is replicated, modified and repaired, discovering these repair pathways has opening the doors for researchers to try and reverse the process and cause damage to unwanted DNA present in the body – such as those found in cancer cells. If the repair of unwanted cells can be ‘switched off’, their efficient replication may be halted and the disease could be stopped in its tracks. Some treatments are already in use which have this mode of action, an example being Olaparib – a drug which inhibits the growth of some hereditary cancers.
This year’s Nobel prize in Chemistry not only honours work which has greatly expanded knowledge of the field, but which has had tremendous implications on the way we understand our own bodies, and how we can preserve them and keep them healthy. There’s still a great deal of scope for this field, but thanks to Lindahl, Sancar and Modrich there is solid ground to be built on for the future.