Dissecting the Nucleosome: Single-Molecule Studies of Subnucleosomal Structure and Dynamics

Abstract

The entire blueprint of all living things is encoded in their genomes, which consist of DNA strands. The genome of a complex organism like ourselves can be several meters long. One of the miracles of nature is that such DNA molecules can be stored in the micron-sized nucleus of eukaryotic cells. For this purpose, the relatively large genome of eukaryotes has to be tightly packed while still remaining accessible for vital cellular processes such as replication, transcription, and repair. This is achieved by the organization of the eukaryotic genome into a hierarchical nucleoprotein assembly termed chromatin. Its fundamental unit is the nucleosome, which comprises a short piece of DNA wrapped around a disk-shaped core of eight histone proteins in a left-handed superhelix. As such, nucleosomes constitute the first level of DNA compaction and are assigned a key role in the regulation of the genome to maintain the proper functioning and viability of eukaryotic cells. Hence, detailed knowledge of this fascinating complex is crucial for understanding fundamental processes of life. This thesis deals with investigations of the structure and dynamics of a nucleosomal substructure called tetrasome at the single-molecule level.BN/Nynke Dekker La