The Contribution of Initial and Altered Genome Organization to DNA Damage and Repair

The three-dimensional genome structure is critical for the regulation of gene expression and DNA damage repair. Our previous study characterized the alteration of genome architecture following radiation-induced DNA damage. However, it is still unknown how radiation-induced DSBs are distributed across the genome, how the initial genome structure influences the distribution of DSBs, how the modification of chromatin structure through pretreatment impacts DNA damage, and how the anti-cancer drugs alter 3D genome organization in healthy cells. CHAPTER II summarizes one of the key phenomena in alteration of 3D genome organization, compartment shifting, across multiple situations. CHAPTER VI focuses on the potential mechanism of 3D genome reorganization after radiation-induced DNA damage. CHAPTER IV identifies the distribution of radiation-induced DSBs in BJ-5ta and GM12878 cells and how the distribution correlates with the initial 3D genome architecture using END-seq. CHAPTER III used HDACi to modulate chromatin architecture and examined the impact of enhanced genomic accessibility on radiation-induced DNA damage. CHAPTER V explores how an anti-cancer drug curaxin impacts cell viability, DNA damage response, and 3D genome organization in non-cancerous cells. Overall, these findings suggest that the initial 3D genome structure is important to determine the genomic susceptibility to radiation-induced DNA damage, which could be applied in cancer therapy.