Our DNA contains the information for the behaviour of our cells, which together form our body. For the body to develop and maintain its proper function, the DNA needs to be transmitted from one cell, known as parental cell, to two new cells. To allow this to happen, the DNA is first duplicated, after which the two identical copies are accurately distributed to generate two identical ‘daughter cells’. This distribution is called mitosis. It is essential that this transmission of genetic information happens without errors, as incorrect distribution can lead to developmental disorders and cancer.

The DNA in each of our cells is meters in length. Cells however are very small. The DNA therefore has to be carefully folded into our cells. When cells prepare to divide, the DNA is compacted into X-shaped structures, consisting of two identical rods that are connected in the middle. This compaction is essential for the correct transmission of genetic information to the daughter cells. The X-shape of mitotic chromosomes was first observed in the 19th century. However, the mechanism behind the formation of these X-shaped structures has remained an enigma. In this thesis, we investigate two key players in the formation of X-shaped chromosomes. These players are cohesin and condensin.

Cohesin and condensin are members of the family of Structural Maintenance of Chromosomes (SMC) complexes. Both complexes are ring-shaped and can interact with DNA, but cohesin and condensin play distinct roles in the formation of mitotic chromosomes. Cohesin holds together the two identical copies of the DNA, through a mechanism known as sister chromatid cohesion. Cohesin maintains these connections until the right moment, and hereby ensures that both daughter cells will receive a complete copy of all the DNA. As cells enter mitosis, condensin compacts the genome by converting dynamic DNA treads into a dense array of DNA loops.@en