DNA-protein cross-links (DPCs) are bulky DNA lesions formed when proteins become covalently trapped on DNA. DPCs block DNA replication and repair, potentially contributing to genotoxicity and carcinogenesis. In the present study, site-specific, structurally defined DPCs were prepared via semi-synthetic approaches involving click chemistry and post-synthetic reductive amination. Synthetic DPC lesions were characterized by gel electrophoresis and mass spectrometry and incorporated into double-stranded M13 plasmids, which were introduced into mammalian cells to investigate their repair in vivo.

Synthesis and repair of site-specific DNA-protein cross-links

244th National Meeting (2012)

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