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13 1  Introduction  15 1.1 Chromatin  15 1.2 Nucleosome core structure  17 1.3 Linker histones  21 1.4 Linker histone binding to nucleosome  22 1.5 Higher order structures of chromatin  25 1.6 Chromatin as drug target  28 1.7 Metals in medicine  29 1.8 Project aims  35 2  Materials and Methods  36 2.1 Materials  36 2.1.1 Chemicals  36 2.1.2 Buffers and Solutions  37 2.1.3 Competent Cells and Media  40 2.1.4 Enzymes and Reaction Buffers  41 2.1.5 Gels and Loading Buffers  41 2.1.6 Equipments  43 2.1.7 DNA and Protein Constructs  44 2.1.8 Crystallization Screening Kits  44 2.1.9 Metal‐based Compounds  45 2.2 Methods  47 2.2.1 Palindromic DNA Production  47 2.2.2 Non‐palindromic DNA Production  50 2.2.3 DNA Array Production  51 2.2.4 Xenopus Core Histones Production  52 2.2.5 Human Core Histones Production  54 2.2.6 Linker Histone Production  56 2.2.7 Histone Octamer Production  58 2.2.8 Reconstitution of Nucleosome and Nucleosome Core Particle  58 2.2.9 Reconstitution of Nucleosome Array NUC601‐36‐177  59

Characterizing the nucleosome site selectivity, adduct structures and impact on chromatin for a variety of metal-based anticancer compounds and structural studies of nucleosome-linker histone interactions