AI Article Synopsis
- The text discusses how post-translational modifications, specifically by ubiquitin (Ub) and SUMO, play a critical role in regulating DNA replication.
- Researchers have observed that areas around the replisome (where DNA replication occurs) have high levels of SUMO and low levels of Ub, while mature chromatin shows the opposite pattern.
- The study identifies the enzyme USP7 as crucial for maintaining this SUMO-rich environment and reveals that inhibiting or deleting USP7 causes Ub to accumulate on SUMOylated proteins, moving them away from replication sites, which could have implications for developing cancer treatments.
Article Abstract
Post-translational modification of proteins by ubiquitin (Ub) and Ub-like modifiers regulates DNA replication. We have previously shown that chromatin around replisomes is rich in SUMO and poor in Ub, whereas mature chromatin exhibits an opposite pattern. How this SUMO-rich, Ub-poor environment is maintained at sites of DNA replication in mammalian cells remains unexplored. Here we identify USP7 as a replisome-enriched SUMO deubiquitinase that is essential for DNA replication. By acting on SUMO and SUMOylated proteins, USP7 counteracts their ubiquitination. Inhibition or genetic deletion of USP7 leads to the accumulation of Ub on SUMOylated proteins, which are displaced away from replisomes. Our findings provide a model explaining the differential accumulation of SUMO and Ub at replication forks and identify an essential role of USP7 in DNA replication that should be considered in the development of USP7 inhibitors as anticancer agents.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869841 | PMC |
| http://dx.doi.org/10.1038/nsmb.3185 | DOI Listing |
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