Meet the molecular matchmakers
We all make mistakes. And when we do, we are usually anxious to put things right as soon as possible. But sometimes it can be difficult to know what ‘right’ is.
What about correcting mistakes in DNA? Because a new copy of DNA is made by copying one of the old threads of genetic information it might seem straightforward to know what is right. The old strand has the right information and any errors in the new strand – such as a ‘letter’ of genetic code that doesn’t pair up with what is written on the old strand or a few extra letters inserted by accident – need to be rectified. Easy in principle, but when the cell’s molecular repair machinery is faced with double-stranded DNA how can it tell the old and new strands apart?
Understanding the inner-workings of cells is a challenging business and so scientists often start by studying something far simpler than human beings – bacteria. Making correct copies of DNA is so fundamentally important for life that bacteria and humans have similar repair systems. Scientists have found that in bacteria a chemical label - called a methyl group - is added to each strand of DNA after it is made, but not straightaway. This means that there is a window of time when the old strand has its methyl label and the new strand does not; time for the repair machinery to distinguish the ‘right’ old strand from the potentially ‘wrong’ new strand.
So, after you’ve realized that you’ve made a mistake and know what the right answer should be, how do you make the correction? If you make a mistake on a piece of paper you might throw that sheet in the rubbish bin and start afresh or you might just erase the mistake and insert the correction. Throwing away a sheet of paper for the sake of spelling mistake seems very wasteful, as does throwing away an entire strand of DNA for a small error. Ever energy-conservation conscious, cells opt for molecular eraser.
In bacteria a mistake in the new DNA strand is recognized by proteins called MutS and MutL. 
They activate another protein, MutH, which acts like a pair of scissors to snip through the DNA near to the incorrect letter. A section of DNA – including the error – is unwound by yet another protein called UvrD, and chewed off. Then a replacement section of DNA is inserted, letter-by-letter, and the snip is sealed up again. Similarly, even if you have only got one letter wrong in a word, you might erase the complete word and write it again correctly. With the corrected word back in place, the whole sentence is seamless as though you never made the mistake.
In mammals, such as ourselves, the principles are similar to those found in bacteria. However, the details seem to be more complicated, perhaps unsurprisingly considering how much more complex a human is than a bacterium. Researchers have identified human versions of proteins such as MutS and MutL; working out the details of how mistakes are recognized, erased and corrected as each of our cells gets ready to divide is an active area of ongoing research.
Mary Muers