Influence Of Deubiquitinating Enzymes On Mutagenesis In Saccharomyces Cerevisiae

Abstract

In recent years, it became clear that the mutagenic effect of base alterations in a DNA template is dependent on bypass synthesis, carried out by one or more translesion polymerases. A critical role for proliferating cell nuclear antigen (PCNA) and its ubiquitination following DNA damage has been established. Among Saccharomyces cerevisiae deletion mutants in which UV mutagenesis is compromised, we identified and characterized a mutant of the ubiquitin recycling protein Doa4. Similar cases may be represented by Doa1, previously described by others, as well as Bro1 and Ubi4. We discuss overall altered ubiquitin levels or failure to deubiquitinate specific target proteins as likely explanations. This study is of relevance for understanding and possibly modifying the mutagenic effect of DNA-damaging agents in environmental toxicology, cancer treatment and cancer prevention.