Multiprotein complexes separate from DNA repair for a few seconds
Repair of damaged DNA takes hours
15 June 2010
Researchers at the University of Amsterdam (UvA) have discovered which processes occur in the repair of damaged DNA.
Researchers at the University of Amsterdam (UvA) have discovered which processes occur in the repair of damaged DNA. Measurements indicate that a number of multiprotein complexes accumulate for several hours at the site of a DNA damage. They require this time to repair the damaged DNA. Paradoxically, the research also showed that the individual proteins seperate independently from the DNA every ten to sixty seconds only to bind once more later. Their findings were recently published in the Journal of Cell Biology.
Our DNA is involved in many crucial processes in the cell. Different groups of proteins are involved in these processes. If these proteins have nothing to do they move independently of one another through the nucleus where DNA is stored. As soon as something has to happen with the DNA, a recognition protein determines the correct position on the DNA. At this point numerous proteins come together which are necessary to repair the damaged DNA. The researchers looked at how it is possible that so many proteins can work together effectively to carry out a specific task on the DNA, while these proteins have no affinity with each other if they are not bound to the DNA.
The UvA researchers, led by Professor Roel van Driel, focused on the repair of mammalian DNA damaged by UV light. The measurements revealed that the proteins assemble for several hours at the site of DNA damage. The proteins needed the time to repair all damaged DNA. Paradoxically, the research also showed that the individual proteins seperate independently from the DNA every ten to sixty seconds only to bind once more later. This can be compared with a meeting where people have to perform a task together in the meeting room, while continuously leaving the room independently of each other. The measurements on living cells were performed by Martijn Luijsterburg in collaboration with the Centre for Advanced Microscopy of study.
System explained with mathematical model
Because this complex process can only be understood through the complex interplay of space and time of all the components (DNA and proteins) a mathematical model that integrates all measurements was developed, together with the group of Dr. Thomas Höfer and Gesa von Bornstaedt of the University of Heidelberg,. This model shows how the system works. One conclusion is that the proteins that come together to perform this function do it in a random order instead of a fixed sequence, as generally assumed. The researchers also discovered that the protein that recognizes damaged DNA take unexpectedly long to bind to damaged DNA: on average it takes about 30 minutes to bind. Moreover, they bind surprisingly loosely. The slow and loose binding seems to be a compromise between, on the one hand, fast but not accurate repair and on the other hand slow, but very accurate, repair. In short, this biological system shows that precise work takes time.
M. Luijsterburg, G. Von Bornstaedt, A. Gourdin, A. Politi, M. Moné, D. Warmerdam, J. Goedhart, W. Vermeulen, R. Van Driel en T. Höfer: Stochastic and Reversible Assembly of a Multiprotein DNA Repair Complex Ensures Accurate Target Site Recognition and Efficient Repair. J Cell Biol. (2010: 189, pag. 445-63).