Fig. 6: Model.

Diagram predicting how ISG15 may be functioning at replication forks to maintain genomic stability. ISG15 proficient cells: ISGylation stabilizes protein interactions and regulates protein functions at stalled replication forks, thus promoting faithful DNA replication. ISG15 deficient cells: No ISGylation of replication fork associated proteins upon fork stalling. Depletion of proteins required for fork stability and/or loss of protein regulation results in replication stress phenotypes. Red cross represents loss of protein activity. See main text for details. Source data are provided with this paper.