Cdc48/p97 segregase: Spotlight on DNA-protein crosslinks

Area of Science:

• Molecular biology
• Cellular processes
• DNA repair mechanisms

Background:

• Cdc48/p97 (VCP) is an ATP-dependent molecular chaperone vital for cellular functions.
• It plays a key role in the DNA damage response by targeting ubiquitinated and SUMOylated chromatin substrates.
• DNA-protein crosslinks (DPCs) pose a significant threat to genomic integrity.

Purpose of the Study:

• To review the structure, mechanism, and cellular functions of Cdc48/p97.
• To emphasize the current understanding of DPC repair pathways.
• To discuss the therapeutic potential of targeting p97 in DPC repair.

Main Methods:

• Literature review focusing on Cdc48/p97 and DPC repair.
• Analysis of existing studies on chaperone function in DNA repair.
• Synthesis of data across multiple organisms.

Main Results:

• Cdc48/p97, with cofactors like Ufd1-Npl4, is central to unfolding and processing DPCs.
• The chaperone targets ubiquitinated and SUMOylated substrates on chromatin.
• Evidence supports its pivotal role in DNA damage response and DPC removal.

Conclusions:

• Cdc48/p97 is a key player in multiple DNA repair pathways, especially DPC repair.
• Understanding its mechanism offers insights into maintaining genomic stability.
• Targeting p97 presents a potential therapeutic strategy for DPC-related conditions.