Our DNA is what defines us: as a species and as individuals. Maintaining DNA is something your body absolutely needs to do as a first step to keeping everything else in line. As many of us are aware, damaged DNA can lead to myriad health problems including all kinds of cancer. The structure and the sequence of DNA is also the life-code we pass on to our children. You can't give away holey hand-me-down genes.
Unfortunately, our DNA is not kept under lock and key in a secure velvet box (as you might predict for so precious a molecule), but is accessed and processed constantly. This means a lot of wear and tear needing to be repaired. To manage the damage, your cells have enzymes for DNA repair. These proteins recognize damaged DNA and surgically remove specific corrupted segments to make way for replacement parts.
These enzymes (5’ structure-specific nucleases) belong to one family with a single structure, but somehow each recognizes a different type of DNA damage. Picture the DNA as a thick rope made by twisting two ropes together and then damaged by slicing or weakening one strand, cutting both together, cutting out a portion of one, or looping in an extra segment in one strand. Until now, no one knew how all of these forms could be recognized by a single basic enzyme structure with each individual enzyme only working on one type of damage.
This week in the journal Cell, a group of researches lead by Dr. Lorena Beese published results that explain the Swiss Army knife-like ability of this family of enzymes. They explain that the structure of the enzyme binds to a very sharp bend in the DNA that can only occur when it is damaged (picture the thick rope being harder to bend than its corrupted counterpart). Inside the active site of the enzyme, the two strands fray apart, making all the types of damage look very similar.
This explains why all these flavours of DNA damage are processed by the same type of enzyme, but how are the individual proteins able to distinguish between them? The same research group found that it is most likely lock and key-like recognition sites on the outside of the protein that are able (or unable) to bind the extra loops and strands that make the different damaged DNA structures unique. In this way, relatively minor alterations to the enzymes’ overall structure make them specific, allowing evolution to recycle the same tool for multiple purposes.
Nature hates to reinvent the wheel. Elegant evolutionary problem solving like this is what allows evolution to move forward while conserving energy. And let me tell you, our cells are hungry for energy, mmmmm...
Have you ever had to deal with a tangled mess of holiday lights or try to coil up a long extension cord?
ReplyDeleteHave you ever tried to cut rope strands and reattach them without tying a knot or adding a clamp or glue, yet retain the rope's original strength, length and shape?
This is the magic of DNA and the enzymes that maintain it.