Yeast Rad5 Protein Requi Repair Has a DNA Helicas for Replication Fork Regre

Unrepaired DNA lesions in the template strand can block the progression of the replication fork. In eukaryotes, the Rad6 and Rad18 proteins play a crucial role in regulating the various lesion bypass processes; Rad6, a ubiquitin-conjugating enzyme, exists in vivo in a tight complex with Rad18, a DNA-binding protein (Bailly et al., 1994, 1997). In the yeast Saccharomyces cerevisiae, Rad6-Rad18-mediated ubiquitin conjugation promotes replica-tion through DNA lesions via at least three different path-ways. DNA polymerase (Pol)h and Polz provide means by tination via its role as a ubiquitin ligase by bringing the Mms2-Ubc13 ubiquitin-conjugating activity into close contact with PCNA. Whereas PCNA monoubiquitination activates Polh- and Polz-dependent TLS, polyubiquitina-tion of the PCNA is required for PRR (Haracska et al., 2004; Hoege et al., 2002). Importantly, the ATPase-defec-tive rad5mutant is impaired in PRR to the same degree as is the ubiquitin ligase-defective rad5 mutant (Gangavar-apu et al., 2006). These observations have indicated that both the Rad5 ATPase and ubiquitin ligase activities are indispensable for Rad5 function in PRR. However, the means by which Rad5 ATPase contributes to PRR as well as the molecular mechanism of PRR has remained elusive.Short Articl