DNA–protein crosslink proteases in genome stability

TL;DR

This paper explores enzymes that break DNA-protein crosslinks, which are harmful DNA lesions, and their role in maintaining genome stability and preventing disease.

Contribution

The paper highlights new insights into DPC proteases beyond DPC repair, such as their role in DNA replication and checkpoint control.

Findings

DPC proteases degrade protein components of DNA–protein crosslinks to prevent genomic instability.

These proteases also regulate DNA replication by degrading excess histones and controlling checkpoints.

Dysfunction in DPC proteases is directly linked to human diseases and cancer therapy.

Abstract

Proteins covalently attached to DNA, also known as DNA–protein crosslinks (DPCs), are common and bulky DNA lesions that interfere with DNA replication, repair, transcription and recombination. Research in the past several years indicates that cells possess dedicated enzymes, known as DPC proteases, which digest the protein component of a DPC. Interestingly, DPC proteases also play a role in proteolysis beside DPC repair, such as in degrading excess histones during DNA replication or controlling DNA replication checkpoints. Here, we discuss the importance of DPC proteases in DNA replication, genome stability and their direct link to human diseases and cancer therapy.

DNA–protein crosslink (DPC) proteases digest the protein component of crosslinks that otherwise can cause genomic instability and disease. Ruggiano and Ramadan discuss recent insights into the roles of DPC proteases in the repair of DPCs and beyond.

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