Emerging opportunities to target gene transcription and DNA repair in drug discovery

After the completion of the Human Genome Project, biological research in the post-genomic era has focused on interpreting the biological functions of genes and their products. This includes investigating the regulation of DNA transcription as well as DNA replication and damage repair. These aspects are intricately connected to regulated cell death and diseases associated with it, such as drug-resistant cancers and neurodegenerative diseases. The discovery of novel DNA processing mechanisms that modulate cell death, whether by inducing or inhibiting it, could unveil promising therapeutic strategies for treating diseases related to cell death. DNA processing has several aspects, including DNA transcription, DNA replication, and DNA damage repair. This thesis mainly focuses on the modulation of DNA transcription by histone lysine acetylation and on DNA damage repair mechanisms. The aim of this thesis is to elucidate the regulatory mechanisms of DNA processing involved in regulated cell death and their role in disease pathogenesis, meanwhile developing novel small molecular entities to treat cell-death-related diseases based on the mechanisms identified in this thesis