How the Genome Protects Itself from Intruders

The human genome carries within it all the necessary information for everything that goes on in the human body, for generating proteins, neurotransmitters, and all sorts of other chemicals. But it is constantly under attack from outside factors, such as UV radiation from sunlight and harmful additives in our daily food. Now, researchers are highlighting the exact mechanism employed by cells to clean their DNA strands, and prevent dangerous mutations that could lead to cancer.

The fact that a key enzyme plays a crucial role in alerting the cell that DNA is damaged has been known for quite some time, but the exact method used by the cell to detect the alarm signal emitted by the enzyme has been a thing of best guesses. Scientists from the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, have now published a study in the latest issue of the scientific journal Nature Structural and Molecular Biology, detailing exactly how this is done.

The team also revealed that the cell always has a “vast army” of repair molecules on stand-by, ready to be mobilized at a moment's notice, whenever DNA strands are damaged. But the real remarkable discovery was finding a specific class of proteins, whose only roles are to detect the signals the enzymes put out, and then act to mobilize the cellular defenses. One of the first genetic discoveries was the fact that DNA is organized in complex, protein-filled structures known as chromatines, because of its complexity. An enzyme known as PARP1 was a long time ago discovered to be activated when damage occurs to the acid.

It then produces a molecular signal called PAR, which alerts the cells to the damage. Now, the EMBL team, led by expert Andreas Ladurner, has detected the class of proteins that bind to PAR, and trigger the repair process. By using a complex viewing technique known as X-ray crystallography, the team was able to find out that macrodomain proteins have “pockets” fitting the PAR signal exactly. This means that they bind to each other seamlessly, and that other chemicals or signals are ignored by the protein.

“With these findings we've opened up completely new perspectives to a fifty-year-old field of research. We're very excited of what lies ahead and hope that we'll soon be much closer in understanding how PARP1 and macrodomains together maintain a healthy genome,” says Ladurner, quoted by e!Science News.