DNA–Protein Crosslinks and Their Resolution
Pedro Weickert and Julian Stingele (2022) DNA–Protein Crosslinks and Their Resolution. Annu. Rev. Biochem 91:13.1–13.25
Abstract cited directly from the review article:
Covalent DNA–protein crosslinks (DPCs) are pervasive DNA lesions that interfere with essential chromatin processes such as transcription or replication. This review strives to provide an overview of the sources and principles of cellular DPC formation. DPCs are caused by endogenous reactive metabolites and various chemotherapeutic agents. However, in certain conditions DPCs also arise physiologically in cells. We discuss the cellular mechanisms resolving these threats to genomic integrity. Detection and repair of DPCs require not only the action of canonical DNA repair pathways but also the activity of specialized proteolytic enzymes—including proteases of the SPRTN/Wss1 family—to degrade the crosslinked protein. Loss of DPC repair capacity has dramatic consequences, ranging from genome instability in yeast and worms to cancer predisposition and premature aging in mice and humans.