, that stringy stuff in our
DNA cells, contains four important chemicals: adenine( A), thymine( T), guanine( G) and cytosine( C). These are the nucleobases, the molecules that encode the information for life. They are also willing absorbers of ultraviolet( UV) light, and because of this sunlight can be a major nuisance for our skin.
Absorption is the process where energy from light( a photon) is taken in by a molecule, causing an electron to jump into an‘ excited state’. Excited states are energetic and unstable, and when they occur within a DNA nucleobase, they can initiate the damaging chemical reactions that result in sunburn and skin cancer.
It has been known for many years that UV light attacks DNA, but until just over a decade ago the excited states of DNA were elusive, because they were too short-lived for any lab instrument to record. However, with advances in femtosecond lasers( that produce flashes of light lasting about 10-15 seconds), we can now study these excited states in great detail.
The ability to study very fast processes in DNA is a welcome development, as the behaviour of the excited state in those first few picoseconds( 10-12 seconds) after absorption decides much of what eventually happens to our skin cells. Although this can sometimes result in the adverse health effects mentioned above, our DNA is actually quite resilent to UV light and can even be regarded as its own sunscreen.
This self-defence mechanism is most vividly expressed in the behaviour of the individual nucleobases, and represents the first achievement of femtosecond laser studies of DNA. Despite having different chemical structures, the nucleobases all react similarly to the absorption of UV light; they deactivate, fast. Within one picosecond( 10-12 seconds) of absorption, the nucleobase excited states have lost most of their ability to cause damage. Computer
Fixing DNA a flash
Páraic Keane writes that the first few trillionths of a second makes a big difference in how sunlight affects our DNA
simulations show that this is achieved by a process of molecular gymnastics. The nucleobases, which are usually flat, distort their shape and release the excess energy through vibrations of the chemical bonds, which persist for about ten picoseconds after the excited state has been swiched off. In effect, the high energy UV light is rapidly dispersed through a series of lower energy processes, which can be described simply as‘ heat’, but is more technically known as‘ ultrafast internal conversion’. No bonds are broken, and the very rapid quenching of the excited state minimises the chance of any harmful reactions happening.
However, if the chemical structure of a nucleobase is altered slightly, the deactivation can slow considerably, and the potential for chemical reactivity increases. It appears, therefore, that the nucleobases are optimised to survive UV radiation. This survival feature may partly explain why A, T, G and C became building blocks of life. Nowadays, we can be thankful that atmospheric oxygen and the ozone layer removes most of the dangerous UV rays( UVC and most UVB) before they reach us, but this protection may not have been present billions of years ago when the chemistry of primordial life was evolving. As a result, a high tolerance for UV light was likely to have been a prerequisite for biological success.
The ultrafast deactivation of the excited nucleobases is a neat example of natural selection on the molecular scale, but cannot completely explain the interactions of UV with DNA. In double-stranded DNA the nucleobases are all joined up by a sugar / phosphate backbone, they are base-paired with their complement in another strand through hydrogen bonds( A with T, G with C), and they stack on top of other
nucleobases within their own strand. All these features are significant, as the behaviour of excited states is very sensitive to chemical structure.
In fact, having other nucleobases so close together is where much of the trouble starts. When two thymine nucleobases appear next to each other in a sequence, UV light can cause them to fuse together to form a dimer, which inhibits further replication of the strand. Although relatively common, these TT dimers are well repaired by enzymes in the cell that recognise and remove the damaged sequences. By contrast, cytosine dimers( CC) are rarer, but are much more dangerous because they are poorly repaired. One reason is that they rapidly transform to uracil( the nucleobase that replaces thymine in RNA), which is complementary to A rather than G. If the damaged strande is copied, CC becomes TT, and a potentially cancerous mutation occurs.
In general, UV damage to DNA is concentrated at the‘ pyrimidines’( T and C) rather than the larger‘ purines’( A and G). This is mainly due to the structural features of pyrimidines versus purines, but ultrafast laser experiments have thrown up some other intriguing coincidences. When the sugar / phosphate molecules are attached to T or C( but not A or G), about 15 per cent of the UV energy diverts through another excited state, which retains the energy up to 100 times longer than the nucleobase alone. These are known in spectroscopy parlance as‘ dark’ states, a rather apt name when neither the reasons nor consequences of their formation are understood. It is possible that they are involved in the formation of dimers, although some experiments suggest that these dimers are formed too rapidly for dark states to matter. Alternatively, they could be involved in the other photo-
SCIENCE SPIN Issue 58 Page 10