DNA Doctors
Wim Vermeulen - afd Genetica
The carrier of genetic information; DNA, is constantly at risk of being damaged by environmental influences, such as UV-light present in sunlight and chemicals that react with DNA, like cigarette smoke and car combustion products. One of the main functions of DNA i.e. reading and transferring its information by the process of transcription is severely affected by the presence of DNA damage. Blocked transcription ultimately causes premature cell death, as such DNA lesions are an important driver of ageing. Moreover, DNA damage causes inaccurate copying of the genome, thereby introducing mutations. When essential genes are mutated vital functions of the cell are affected, including the regulation of cell growth. Uncontrolled cell growth is an important step in the process of cancer development.
To circumvent these deleterious consequences of DNA damage all cells contain different DNA repair mechanisms to remove these DNA damages. A large number of enzymes constantly search for DNA damage with specific repair enzymes for different types of damage. If damage is detected these enzymes bind to it and subsequently recruit other enzymes that repair the damage. The importance of an intact DNA repair system becomes specifically clear in patients that suffer from inherited defects in one of the DNA repair systems and are commonly accompanied with extreme cancer susceptibility and exhibit premature ageing features.
Most of our knowledge on the different DNA repair processes is based on biochemical analysis after extraction of enzymes from cells and analysis in the test-tube. Little is known, however, about the way DNA is maintained and repaired in its most relevant context: the living cell. The current challenge in DNA repair research is to gain knowledge on how these processes are regulated and communicate with each other. It is of great importance to get insight in how DNA repair is organized in living cells, how it prevents mutation induction and avoids cancer in an intact organism.
In the lab we are mainly interested on how UV-light induced DNA damage is repaired. To understand the process of DNA repair we pursue a multi-disciplinary approach. A large variety of different techniques are operational to study in detail the molecular process of DNA repair. The research in the laboratory currently focuses on analyzing DNA repair proteins in living cells and animals, by using fluorescently marked DNA repair enzymes. By the use specialized microscopes the proteins can be visualized and their dynamic behavior can be monitored, as such the living cell forms an ideal ‘test tube’ to analyze the molecular mechanism of genome protection. De voertaal van deze stage is Engels.