Ubiquitin chain editing promotes p97/VCP-dependent removal of RPA from DNA.

Ubiquitin chain editing by ZUP1 promotes p97/VCP-dependent removal of RPA from ssDNA, crucial for DNA repair and genome stability.

• Why it matters: Understanding how ubiquitin signaling regulates proteins on ssDNA is vital because improper regulation can lead to genome instability and disease.
• What they did: The study used human cells to identify that ZUP1 deubiquitinase selectively removes K63 linkages from branched K48-K63 ubiquitin chains on RPA, facilitating its removal.
• The result: This ubiquitin chain editing enables p97/VCP to extract RPA from ssDNA, preventing RPA trapping and reducing genome instability, highlighting a key mechanism in DNA repair.