My PhD dissertation focused on DNA-protein interactions and the recognition of specific DNA sequences and structures. I discovered that acidic amino acid residues (Asp/Glu) play a crucial role by exhibiting a preference for cytosine. Their contribution to binding affinity depends on nearby cytosines, balancing electrostatic repulsion with specific interactions. Acidic residues act as negative selectors, discouraging non-cytosine binding, but can be favorable with increasing proximal cytosine count. They exclusively recognize cytosine due to electrostatic repulsion with adenine's N7 atom and stronger hydrogen bonding. In another aspect of my research, I explored conformation-specific DNA recognition. I found that the EXOG protein prefers A-DNA and selectively recognizes RNA/DNA chimeric duplexes. Specific arginine residues induce the A-DNA conformation when EXOG binds to DNA/DNA duplexes, providing insights into mitochondrial replication and base excision repair. Furthermore, I investigated the DHX36 helicase, which recognizes G-quadruplexes (G4s) through its DSM and OB subdomains. The planar face of a G-tetrad and the specific backbone conformation of a G-tract are critical features in this interaction. The DSM and OB subdomains cooperatively recognize these distinctive features of parallel G4s. Importantly, the recognition by DSM is mediated through van der Waals contacts and hydrophobic interactions, exhibiting a preference for the accessible 5'-side of the G4 structure.
Authors
Additional information
- Category
- Doktoraty, rozprawy habilitacyjne, nostryfikacje
- Type
- praca doktorska pracowników zatrudnionych w PG oraz studentów studium doktoranckiego
- Language
- angielski
- Publication year
- 2023
