Crosslinking pathways, dynamics, and kinetics between guanosine and lysine following one- versus two-electron oxidation of guanosine.

ABSTRACT: DNA-protein crosslinks (DPCs) remain as a poorly understood DNA lesion. Herein, crosslinking between guanosine and lysine was explored using a model system comprising 9-methylguanine (9MG) and CH3NH2. Crosslinking was induced by one-electron oxidized 9MG•+ radical cations and doubly oxidized [9MG - HN2]+ cations, and analyzed as a function of reaction energy using an electrospray ionization tandem mass spectrometer. Experiment was augmented by dynamics simulations and kinetics modeling. Alongside the formation of X-NH2CH3[9MG]•+ (X = C2, C8) via direct addition, 8-CH2NH2[9MG + HN7]+ was discovered as a new crosslink between 9MG•+ and CH3NH2. This crosslink results from methyl-hydrogen abstraction of CH3NH2 by the N7 of 9MG•+, followed by adding •CH2NH2 to [9MG + HN7]+. Notably, crosslinkin

SUBMITTER: Moe MM 

PROVIDER: S-EPMC11879467 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature