A SUMO and ubiquitin code coordinates protein traffic at replication factories.
Post-translational modifications regulate each step of DNA replication to ensure the faithful transmission of genetic information. In this context, we recently showed that deubiquitination of SUMO2/3 and SUMOylated proteins by USP7 helps to create a SUMO-rich and ubiquitin-low environment around replisomes that is necessary to maintain the activity of replication forks and for new origin firing. We propose that a two-flag system mediates the collective concentration of factors at sites of DNA replication, whereby SUMO and Ubiquitinated-SUMO would constitute "stay" or "go" signals respectively for replisome and accessory factors. We here discuss the findings that led to this model, which have implications for the potential use of USP7 inhibitors as anticancer agents.
Spanish National Cancer Research Centre, CNIO, Madrid, Spain.
Emilio
E
Lecona
Spanish National Cancer Research Centre, CNIO, Madrid, Spain.|Science for Life Laboratory, Division of Translational Medicine and Chemical Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.
Oscar
O
Fernandez-Capetillo
D000818:Animals; D004261:DNA Replication; D056890:Eukaryota / Q000235:genetics / Q000378:metabolism; D006801:Humans; D025841:Small Ubiquitin-Related Modifier Proteins; D058207:Sumoylation; D025801:Ubiquitin; D054875:Ubiquitination
D025841:Small Ubiquitin-Related Modifier Proteins; D025801:Ubiquitin
DNA replication; SUMO; USP7; replisome; ubiquitin