The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and two error-free postreplication repair pathways

The RAD6 postreplication repair and mutagenesis pathway is the only major r adiation repair pathway yet to be extensively characterized. It has been pr eviously speculated that the RAD6 pathway consists of two parallel subpathw ays, one error free and another error prone (mutagenic). Here we show that the RAD6 group genes can be exclusively divided into three rather than two independent subpathways represented by the RAD5, POL30, and REV3 genes; the REV3 pathway is largely mutagenic, whereas the RAD5 and the POL30 pathways are deemed error free. Mutants carrying characteristic mutations in each o f the three subpathways are phenotypically indistinguishable from a single mutant such as rad18, which is defective in the entire RAD6 postreplication repair/tolerance pathway. Furthermore, the rad18 mutation is epistatic to all single or combined mutations in any of the above three subpathways. Our data also suggest that MMS2 and UBC13 play a key role in coordinating the response of the error-free subpathways; Mms2 and UbcI3 form a complex requi red for a novel polyubiquitin chain assembly, which probably serves as a si gnal transducer to promote both RAD5 and POL30 error-free postreplication r epair pathways. The model established by this study will facilitate further research into the molecular mechanisms of postreplication repair and trans lesion DNA synthesis. In view of the high degree of sequence conservation o f the RAD6 pathway genes among all eukaryotes, the model presented in the s tudy may also apply to mammalian cells and predict links to human diseases.