PhD defence R.H.W.E. (Robin) van der Weide

Dissertation in short:

The average cell has a nuclear of 2 to 10 microns is size—less that 1% of a millimetre. A nucleus encloses a full genome of approximately 2 metres in length. While it is already no small feat that all this DNA fits inside the nucleus, it is even more incredible that it is folded the same way in every of the billions of cells in the human body. These folds (or loops) have functions in regulating genes and mis-foldings can lead to diseases and developmental disorders. Before we can find and correct faulty loops in the future, we first have to know how DNA-organisation is formed and maintained. We show that a ring-shaped protein complex (Cohesin) plays an important role in this organisation. The formation of loops turns out to be a dynamic proces, in which Cohesin is continuously being loaded on and released of the DNA. The longer Cohesin is on the DNA, the longer loops are. This had large effects on other layers of gene-regulation, which shows that the Cohesin-mediated organisation is very important. With out experimental studies, we are the first to validate a hypothesis from 2001 on the formation of loops.