Investigation of DNA perturbation and its effect on protein–DNA recognition code

Protein–DNA interactions are essential for molecular and cellular mechanisms, such as gene expression, replication, and damage repair. These processes are crucial for maintaining cell viability, and failure in these processes can lead to mutagenesis and cancer development. It is well established that proteins use both the one-dimensional sequence and the three-dimensional shape of DNA to bind and act on their target sites. These DNA binding proteins, with intercalation and groove binding modes, are known to induce the perturbation of the geometrical, chemical, and mechanical characteristics of DNA. I will present how some of these perturbations in the DNA affect protein–DNA interactions, particularly on the superfamilies DNA binding protein (i) transcription factors and (ii) repair enzymes. The general approach in my study is to combine our lab expertise in high-throughput measurements, and integrate it with traditional biochemical assays, and computational genomics, to investigate different protein–DNA mechanisms comprehensively. Our results reveal determining factors of the protein-DNA recognition code and could advance our understanding of the design principles governing DNA–protein interactions and lay the foundation for a deep molecular understanding of the gene expression program, mutagenesis, and the development of genetic diseases.