共价DNA-蛋白交联(DPCs)是广泛存在的DNA损伤，干扰着基本的染色质过程，如转录或复制。本次综述试图概述细胞DPCs形成的来源和原则。DPCs是由内源性活性代谢产物和各种化疗药物引起的。然而，在某些情况下，DPCs也会在细胞内生理上产生。我们讨论细胞的机制来解决这些对基因组完整性的威胁。检测和修复DPCs不仅需要标准的DNA修复途径的作用，还需要特殊的蛋白酶酶活——包括SPRTN/Wss1家族的蛋白酶——来降解交联的蛋白质。DPC修复能力的丧失有着极具影响力的后果，从酵母和蠕虫的基因组不稳定性，到小鼠和人的癌症易感性和过早衰老。

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.