The DNA Damage Tolerance in Yeast <i>Saccharomyces cerevisiae</i>
In eukaryotes, DNA damage tolerance (DDT) is mediated by two mechanisms. The first is mediated by proteins of homologous recombination repair (HRR). The second is under the control of the RAD6-epistatic group of genes, and is divided into two more paths: error-free and error-prone. The error-prone mechanism called translesion synthesis (TLS) is carried out by specialized TLS-DNA polymerases. TLS is a significant source of mutational changes in DNA. On the contrary, in the implementation of the RAD6-dependent error-free DDT mechanism, a relatively higher accuracy of DNA synthesis is provided due to the use of an intact sister chromatid or a homologous chromosome as a template for the continuation of replication. In this case, after stopping the replication fork at the damage, the 3'-end of the synthesized strand is transferred to an intact homologous DNA molecule, the synthesis continues for some length on a new template, and then the elongated strand is transferred back to the original chromatid. Inactivation of most of the genes that control the error-free DDT mechanism either does not affect the level of UV-induced mutagenesis or decreases it. Exceptions include genes belonging to the epistatic group HSM3. Mutations in the genes of this group lead to a significant increase in the frequency of UV-induced mutagenesis. In this review, the authors consider an unmistakable branch of DDT and attempt to substantiate the role of genes of the HSM3-epistatic group in a series of molecular events that lead to an unmistakable bypass of replication blocking lesions in budding yeast.