In yeast, the Rad6-Rad18 ubiquitin conjugating enzyme plays a critical role in promoting replication although DNA lesions by translesion synthesis (TLS). In striking contrast, a number of studies have indicated that TLS can occur in the absence of Rad18 in human and other mammalian cells, and also in chicken cells. In this study, we determine the role of Rad18 in TLS that occurs during replication in human and mouse cells, and show that in the absence of Rad18, replication of duplex plasmids containing a cis-syn TT dimer or a (6-4) TT photoproduct is severely inhibited in human cells and that mutagenesis resulting from TLS opposite cyclobutane pyrimidine dimers and (6-4) photoproducts formed at the TT, TC, and CC dipyrimidine sites in the chromosomal cII gene in UV-irradiated mouse cells is abolished. From these and other observations with Rad18, we conclude that the Rad6-Rad18 enzyme plays an essential role in promoting replication through DNA lesions by TLS in mammalian cells. In contrast, the dispensability of Rad18 for TLS in chicken DT40 cells would suggest that the role of the Rad6-Rad18 enzyme complex has diverged considerably between chicken and mammals, raising the possibility that TLS mechanisms differ among them.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Reference||Annotation Extension|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Conditions||Strain||Source||Reference|