Chapter 7. DNA–Protein Cross-links: Formation, Genotoxicity and Repair

DNA–protein cross-links are bulky DNA adducts that form both endogenously and following exposure to a variety of exogenous agents. DNA–protein cross-links can be classified into several categories based on their origin and the size of the protein or peptide. DNA–protein cross-links disrupt chromatin architecture, block DNA replication and transcription, interfere with DNA repair, and induce mutations and genotoxicity. Thus, DNA–protein cross-links contribute to aging and several human ailments, including cancer and neurodegenerative diseases. Because of their substantial size, DNA–protein cross-links pose a major challenge to high fidelity DNA replication and gene expression. Accordingly, their removal is critical for maintaining the integrity of the genome, and distinct repair pathways have evolved to remove DNA–protein cross-links from DNA. This chapter attempts to summarize the current state of knowledge of the formation of DNA–protein cross-links, biological effects, and the modes of repair.