Genetic analysis of ionizing radiation-induced mutagenesis in Saccharomyces cerevisiae reveals TransLesion Synthesis (TLS) independent of PCNA K164 SUMOylation and ubiquitination

摘要: Ionizing radiation-induced mutagenesis (IR-IM) underlies a basis for radiation associated carcinogenesis as well resistance to therapy. This process was examined in Saccharomyces cerevisiae using an array of isogenic DNA repair deficient mutants. Mutations inactivating homologous recombination (rad51, 52, 54) or nucleotide excision (rad1, rad10, rad4) caused elevated IR-IM whereas inactivation TransLesion Synthesis (TLS: rad6) severely defective IR-IM. Of the mutations TLS polymerases, rev3 and rev1 equally severe defects rad30 did not significantly affect process. The effects rev3, rev1, rad6 on were epistatic, suggesting requirement both polymerase zeta Rev1p related TLS. Although PCNA K164 SUMOylation/ubiquitination is proposed prerequisite TLS, defect mutant worse than epistatic pol30K164R mutant, which had been mutated abolish such modifications. These results suggested that occurs absence modification. Further analysis simultaneously SUMOylation mono-ubiquitination (rad18 siz1) revealed these modifications redundantly affected NHEJ. A genetic model based observations proposed.