Photoinduced Electron Transfer-Triggered g-C3N4\Rhodamine B Sensing System for the Ratiometric Fluorescence Quantitation of Carbendazim

A common and insidious DNA damage is 8-oxoguanine (8OG), bypassed with low catalytic efficiency and high error frequency by polymerases (Pols) during DNA replication. This is a fundamental process with far-reaching implications in cell function and diseases. However, the molecular determinants of how 8OG exactly affects the catalytic efficiency of Pols remain largely unclear. By examining ternary deoxycytidine triphosphate/ DNA/Pol complexes containing the 8OG damage, we found that 8OG consistently adopts different conformations when bound to Pols, compared to when in isolated DNA. Equilibrium molecular dynamics and metadynamics free energy calculations quantified that 8OG is in the lowest energy conformation in isolated DNA. In contrast, 8OG adopts high-energy conformations often characterized by intramolecular steric repulsion when bound to Pols. We show that the 8OG conformation can be regulated by mutating Pol residues interacting with the 8OG phosphate group. These findings propose the 8OG conformation as a factor in Polmediated processing of damaged DNA.

Automated summary

A common and insidious DNA damage, 8-oxoguanine (8OG), is bypassed with low efficiency and high error rate by polymerases (Pols) during DNA replication. The molecular determinants of how 8OG affects Pols' efficiency remain unclear. This study discovered that 8OG adopts different conformations when bound to Pols compared to isolated DNA. Mutating Pol residues interacting with the 8OG phosphate group can regulate the conformation, suggesting its importance in Pol-mediated processing of damaged DNA.