The Role of Chromatin Assembly Factors in Induced Mutagenesis at Low Levels of DNA Damage

The problem of low-dose irradiation has been discussed in the scientific literature for several decades, but it is impossible to come to a generally accepted conclusion about the presence of any specific features of low-dose irradiation in contrast to acute irradiation. We were interested in the effect of low doses of UV radiation on the physiological processes, including repair processes in cells of the yeast Saccharomyces cerevisiae, in contrast to high doses of radiation. Cells utilize excision repair and DNA damage tolerance pathways without significant delay of the cell cycle to address low levels of DNA damage (such as spontaneous base lesions). For genotoxic agents, there is a dose threshold below which checkpoint activation is minimal despite the measurable activity of the DNA repair pathways. Here we report that at ultra-low levels of DNA damage, the role of the error-free branch of post-replicative repair in protection against induced mutagenesis is key. However, with an increase in the levels of DNA damage, the role of the error-free repair branch is rapidly decreasing. We demonstrate that with an increase in the amount of DNA damage from ultra-small to high, asf1Δ-specific mutagenesis decreases catastrophically. A similar dependence is observed for mutants of gene-encoding subunits of the NuB4 complex. Elevated levels of dNTPs caused by the inactivation of the SML1 gene are responsible for high spontaneous reparative mutagenesis. The Rad53 kinase plays a key role in reparative UV mutagenesis at high doses, as well as in spontaneous repair mutagenesis at ultra-low DNA damage levels.