The p66 and p12 subunits of DNA polymerase delta are modified by ubiquitin and ubiquitin-like proteins.
Modification by ubiquitin-like proteins is now known to be important for the functions of many proteins involved in DNA replication and repair. We have investigated the modification of human DNA polymerase delta by ubiquitin and SUMO proteins. We find that while the p125 and p50 subunits were not modified, the p12 subunit is ubiquitinated and the p66 subunit can be modified by ubiquitin and SUMO3. We show that levels of p12 are regulated by the proteasome, either directly or indirectly, through a mechanism that is not dependent upon p12 ubiquitination. We have mapped two sites of SUMO3-specific modification on the p66 subunit. SUMOylation by SUMO3 but not SUMO2 is unusual: their level of homology is so high that they are normally classified as variants of the same protein. However, our findings show that these two proteins can be distinguished in vivo and may have specific functions.
Liu
Geng
G
Department of Surgery and Molecular Oncology, University of Dundee, Ninewells Hospital, UK.
Warbrick
Emma
E
D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004258:DNA Polymerase III / Q000737:chemistry* / Q000378:metabolism; D004261:DNA Replication; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017434:Protein Structure, Tertiary; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014452:Ubiquitins / Q000378:metabolism
D018809:Proliferating Cell Nuclear Antigen; C492189:SUMO3 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D025801:Ubiquitin; D014452:Ubiquitins; D004258:DNA Polymerase III