Participation of the HIM1 gene of yeast Saccharomyces cerevisiae in the error-free branch of post-replicative repair and role Pol\u03b7 in him1-dependent mutagenesis

E A Alekseeva,V G Korolev,T A Evstyukhina,V T Peshekhonov

doi:10.1007/s00294-020-01115-6

E A Alekseeva, V G Korolev + Show 2 more

Open Access

https://doi.org/10.1007/s00294-020-01115-6

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Abstract

In eukaryotes, DNA damage tolerance (DDT) is determined by two repair pathways, homologous repair recombination (HRR) and a pathway controlled by the RAD6-epistatic group of genes. Monoubiquitylation of PCNA mediates an error-prone pathway, whereas polyubiquitylation stimulates an error-free pathway. The error-free pathway involves components of recombination repair; however, the factors that act in this pathway remain largely unknown. Here, we report that the HIM1 gene participates in error-free DDT. Notably, inactivation RAD30 gene encoding Polη completely suppresses him1-dependent UV mutagenesis. Furthermore, data obtained show a significant role of Polη in him1-dependent mutagenesis, especially at non-bipyrimidine sites (NBP sites). We demonstrate that him1 mutation significantly reduces the efficiency of the induction expression of RNR genes after UV irradiation. Besides, this paper presents evidence that significant increase in the dNTP levels suppress him1-dependent mutagenesis. Our findings show that Polη responsible for him1-dependent mutagenesis.

Highlights

Growing cells need to replicate their DNA with high fidelity to avoid genome instability
To reveal genes, which control the process of induced mutagenesis, we have developed a method of isolation of the yeast mutants affecting the pathway by the phenotype of enhanced induced mutagenesis
We have shown by genetic methods that the HIM1 gene takes part in the error-free branch of post-replicative repair and him1Δ mutant recruitment of Polη in reparative DNA synthesis

Summary

Introduction

Growing cells need to replicate their DNA with high fidelity to avoid genome instability. To prevent a replication arrest, cells employ DNA damage bypass mechanisms that allow the complete replication of the genome in the presence of lesions (Friedberg 2005). These DNA damage tolerance processes contribute to survival after DNA damage and sometimes actively promote the generation of. Current Genetics (2021) 67:141–151 recruitment of DDT components capable of replicating damaged DNA in a TLS Extension of this modification with a polyubiquitin chain by the Ubc13-Mms and the Rad promotes an error-free pathway called template switching (TS). We have shown by genetic methods that the HIM1 gene takes part in the error-free branch of post-replicative repair and him1Δ mutant recruitment of Polη in reparative DNA synthesis

Materials and methods

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Discussion