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The mechanisms by which chromosomes fold into the nucleus constitutes a major question in biology. Our 3.3 billion base-pair genome stretched from one end to the other would cover a length of a few meters. Yet DNA must be structured in such a way that it fits into the confines of the nucleus of only a few microns. This compaction becomes even more extreme when nascent DNA strands move to daughter cells during mitosis. How does the cell accomplish this packaging of DNA while avoiding the formation of knots, entanglements and breakage? How can basic processes such as transcription and replication, which require readily accessible and unknotted DNA, occur within the confined space of the nucleus? How do topoisomerases, which remove knots from crowded DNA molecules, distinguish knotted DNA from unknotted ones? The purpose of this workshop is to improve our understanding of how the genetic material is folded up without entanglements in such a way that it can manage to be properly decoded inside the nucleus.