Abstract

Inside the nucleus at any given moment in time, thousands of molecules are diffusing throughout 3D genome organisation searching for a target DNA sequence. DNA repair machines look for sites of damage to prevent genetic mutations, and transcription factors undergo site specific DNA binding to maintain normal gene expression. The question is how do these molecules efficiently navigate genome architecture to arrive at a target destination? In recent work we developed a series of new fluorescence microscopy methods to track the movement of molecules around the complex DNA networks within the nuclei of live cells. Based on fluorescence correlation spectroscopy, this technology has the spatial and temporal resolution to map the impact genome organisation has on real time molecular trafficking. From using this method we discovered that DNA networks rearrange to create highways that facilitate repair and transcription factor recruitment to target DNA sites. This has given us the first opportunity to start understanding the biophysical rules for traversing the nuclear landscape.

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