The Reparative DNA Polymerase Polη Plays a Key Role in Mutagenesis at Low Doses of UV Radiation in Yeast Saccharomyces cerevisiae

Normally, and under low-dose mutagen exposure, a key mechanism to tolerate DNA lesions in bacterial and eukaryotic cells is the DNA damage tolerance (DDT) system. Two distinct pathways of DDT, the error-prone (translesion synthesis, TLS) and error-free (recombination) ones, function in all eukaryotic organisms. TLS involves the polymerase zeta (Polζ) protein complex (encoded by the REV1, REV3, and REV7 genes) and polymerase eta (Polη) (encoded by the RAD30 gene); these polymerases are evolutionarily conserved from yeast to humans. It was demonstrated that at low doses of UV radiation, high Polη activity plays a key role in mutagenesis, bypassing most of the DNA lesions encountered by the replication machinery. In both high and low doses of UV irradiation, the important role in induced mutagenesis is played by the DNA damage checkpoint. However, the functions of genes involved in the regulation of UV-induced mutagenesis at low and high doses of irradiation often differ. At low doses, the RAD30 gene inactivation resulted in the elevated level of induced mutagenesis, while at high doses, the mutagenesis level was virtually identical to that in wild-type strain. Deletions of the HIM1, HSM3, and HIF1 genes, on the contrary, reduced the high level of mutagenesis characteristic of high doses to wild-type strain level at low doses. These differences apparently characterize local and global checkpoint.