In this study we report that UL44, a viral ortholog of PCNA, is sumoylated on multiple lysines by the cellular factor Ubc9. Importantly, a consistent portion of UL44 is SUMO-modified in HCMV-infected human cells, resulting in ,50% of the protein being modified at late times during virus replication. From a structural point and functional of view, UL44 and PCNA share blotting with anti-SUMO-1 (left panel) and anti-UL44 (right panel) antibodies. For all panels, the arrowhead indicates the unmodified form of UL44, the arrow indicates the immunoglobulin G heavy chain (IgG hc) and the asterisks indicate the sumoylated UL44 forms. doi:10.1371/journal.pone.0049630.g005 some remarkable similarities and some differences. Monomers of UL44 and PCNA are structurally very similar, despite having extremely different primary sequences [2, 9] . However, while PCNA forms toroidal-homotrimers, UL44 binds to dsDNA as a head-to-head homodimer [7, 9] . In addition, PCNA must be loaded onto DNA in an ATP-dependent process by so-called clamp loaders [68] ; in contrast, UL44 directly binds DNA without the need for ATP hydrolysis or accessory proteins [7, 14, 18] .