PCNA SUMOylation protects against PCNA polyubiquitination-mediated, Rad59-dependent, spontaneous, intrachromosomal gene conversion

Publication date: Available online 2 August 2016 Source:Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis Author(s): Agnieszka Halas, Michal Krawczyk, Ewa Sledziewska-Gojska Homologous recombination is crucial in both the maintenance of genome stability and the generation of genetic diversity. Recently, multiple aspects of the recombination machinery functioning at arrested DNA replication forks have been established, yet the roles of diverse modifications of PCNA, the key platform organizing the replication complex, in intrachromosomal recombination have not been comprehensively elucidated. Here, we report how PCNA SUMOylation and/or polyubiquitination affects recombination between direct repeats in S. cerevisiae. Our results show that these PCNA modifications primarily affect gene conversion, whereas their effect on the recombination-mediated deletion of intervening sequence is much less obvious. Siz1-dependent PCNA SUMOylation strongly limits Rad52/Rad51/Rad59-dependent gene conversion. A 5- to 10-fold increase in the frequency of such recombination events is observed in Siz1-defective strains, but this increase is fully suppressed when PCNA polyubiquitination is also compromised. PCNA polyubiquitination can stimulate gene conversion in both PCNA SUMOylation-proficient and SUMOylation-deficient strains. On the other hand, in PCNA polyubiquitination-deficient strains, the lack of PCNA SUMOylation does not affect GC levels. Therefore, we postulate th...
Source: Mutation Research Fundamental and Molecular Mechanisms of Mutagenesis - Category: Cytology Source Type: research
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