Proteins that are covalently bound to DNA constitute a specific type of DNA lesion known as DNA-protein crosslinks (DPCs). DPCs represent physical obstacles to the progression of DNA replication. If not repaired, DPCs cause stalling of DNA replication forks that consequently leads to DNA double-strand breaks, the most cytotoxic DNA lesion. Although DPCs are common DNA lesions, the mechanism of DPC repair was unclear until now. Recent work unveiled that DPC repair is orchestrated by proteolysis performed by two distinct metalloproteases, SPARTAN in metazoans and Wss1 in yeast. This review summarizes recent discoveries on two proteases in DNA replication-coupled DPC repair and establishes DPC proteolysis repair as a separate DNA repair pathway for genome stability and protection from accelerated aging and cancer.

中文翻译：

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DNA-蛋白质交联蛋白水解修复。

与DNA共价结合的蛋白质构成一种特定类型的DNA损伤，称为DNA-蛋白质交联（DPC）。DPC代表了DNA复制进程的物理障碍。如果不进行修复，DPC会导致DNA复制叉停滞，从而导致DNA双链断裂，这是最具细胞毒性的DNA损伤。尽管DPC是常见的DNA损伤，但到目前为止，DPC修复的机制尚不清楚。最近的工作表明，DPC的修复是由两种不同的金属蛋白酶（后生动物中的SPARTAN和酵母中的Wss1）进行蛋白水解来协调的。这篇综述总结了DNA复制偶联的DPC修复中两种蛋白酶的最新发现，并将DPC蛋白水解修复确定为独立的DNA修复途径，可实现基因组稳定性以及防止加速衰老和癌症。