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.

中文翻译：

---

DNA-蛋白质交联及其解析

共价 DNA-蛋白质交联 (DPC) 是普遍存在的 DNA 损伤，会干扰转录或复制等重要染色质过程。本综述旨在概述细胞 DPC 形成的来源和原理。 DPC 是由内源性反应性代谢物和各种化疗药物引起的。然而，在某些条件下，DPC 也会在细胞中生理性地产生。我们讨论解决这些对基因组完整性威胁的细胞机制。 DPC 的检测和修复不仅需要经典 DNA 修复途径的作用，还需要特殊蛋白水解酶（包括 SPRTN/Wss1 家族的蛋白酶）的活性来降解交联蛋白。 DPC 修复能力的丧失会产生严重后果，从酵母和蠕虫的基因组不稳定到小鼠和人类的癌症易感性和过早衰老。