RNF4 and USP7 coordinate spatial regulation of SLX4 stability within the PML nuclear bodies.

ABSTRACT: To protect the genome from the formation of DNA breaks by nucleases involved in DNA repair, cells have evolved multiple levels of regulatory strategies. One key regulator of nuclease activity is the scaffold protein SLX4, which plays important roles in repairing DNA damage induced by mitomycin C (MMC) and camptothecin (CPT) as well as in the resolution of stalled replication forks. Since SLX4 regulates the activity of nucleases such as SLX1, MUS81, and XPF, whose uncontrolled activity could jeopardize genome integrity, the protein level and localization of SLX4 must be tightly regulated. Here, we show that the ubiquitin E3 ligase RNF4 is associated with SLX4 and is responsible for the ubiquitin-dependent proteasomal degradation of excessive SLX4 under normal conditions. Conversely, promyel

SUBMITTER: Jung E 

PROVIDER: S-EPMC12464815 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature