There are some lines of research in the development of science that in all likelihood will not have a ‘breakthrough’ – a big rush of discovery. Instead, the discovery will be piecemeal; sometimes it will be discovery in very small pieces accumulating until a hypothesis is verified. Not all tracks like this are important, but many are. The specific research track in this case is called “DNA repair” – how damaged DNA is detected and repaired in living cells. The ‘small piece’ is an international study that tracks the behavior of proteins that do the repairing.

DNA in all living things is both complex and relatively fragile. DNA damage could be caused by many things including toxins, radiation, or a failure in molecular chemistry. If it happens in one cell, the damage may do nothing, or at worse cause the cell to die. If damage occurs in a reproductive cell (a zygote) it can be an inherited mutation; the consequences of which can go on for generations. Inherited mutations happen, of course, but not all that frequently. However, damage to DNA may be much more frequent. Fortunately Nature has ways of making repairs. How this is done is one of the more important questions in genetics.

Monitoring the strands of DNA with the 22,000 genes and millions of base pairs is a difficult task, as one of the study’s authors, Bennett Van Houten, put it:

“How this system works is an important unanswered question in this field. It has to be able to identify very small mistakes in a 3-dimensional morass of gene strands. It’s akin to spotting potholes on every street all over the country and getting them fixed before the next rush hour.”

[Source: EurekAlert]

The DNA repair workers are (so far as we know) protein molecules. For this study, two such proteins were selected: UvrA and UvrB, which have long been associated with DNA repair. The subject at hand with the DNA was the lab standard bacterium E. coli.

The key to the experiments was using quantum dots (nano-scale crystal semiconductors) that light up in different colors under excitation, to tag and observe the proteins at work. Under microscopic observations it was seen that the UvrA protein randomly jumps from one DNA molecule to the next, staying about 7 seconds before moving on. However, when UvrA formed a complex with two UvrB molecules (UvrAB), the search became more sophisticated and slower. The complex would slide along the DNA strand for as long as 40 seconds before moving to another molecule. Sometimes it was observed that the UvrAB motion would ‘pause,’ apparently checking for structural abnormalities that might indicate DNA damage.

One more aspect of the UvrAB movement was considered significant: If E. coli had only one UvrAB complex, it would take 13 hours to scan the genome in each cell. However, E. Coli doubles (splits into two cells) every 20 minutes, which implies that there are enough protein complexes to complete DNA correction inside that time – about 40 complexes would do the trick.

Much can be learned from direct observation, however, it’s a little like watching an animal in the forest pause by a series of trees. You can see the animal doing it, but don’t know why.

It’s assumed the protein complex is analyzing, but the mechanism of analysis is unknown. It’s also unknown if the UvrAB complex (or similar complex) actually does the repair, or if it signals for some other protein complex(es) to make the repair.

This study has opened a view on the live action of the repair protein, it’s a tool that contributes to the knowledge of the repair patterns. Now the questions about the physical and chemical activity at the molecular level become paramount to answer more questions – more pieces of the research track.