Lsm12 mediates Polη deubiquitination to help Saccharomyces cerevisiae resist oxidative stress

Abstract

In Saccharomyces cerevisiae, the Y-family DNA polymerase {eta} (Pol{eta}) regulates genome stability in response to different forms of environmental stress by translesion DNA synthesis. To elucidate the role of Pol{eta} in oxidative stress-induced DNA damage, we deleted or overexpressed the corresponding gene RAD30, and used transcriptome analysis to screen the potential genes associated with RAD30 to respond to DNA damage. Under 2 mM H2O2, deletion of RAD30 resulted in a 2.2-fold decrease in survival and a 2.8-fold increase in DNA damage, whereas overexpression of RAD30 increased survival and decreased DNA damage by 1.2- and 1.4-fold, respectively, compared with that of the wild-type strain. Transcriptome and phenotypic analysis identified Lsm12 as a main factor involved in oxidative stress-induced DNA damage. Deleting LSM12 caused growth defects while its overexpression enhanced cell growth under 2 mM H2O2. This effect was due to the physical interaction of Lsm12 with the UBZ domain of Pol{eta} to enhance Pol{eta} deubiquitination through Ubp3, and consequently promote Pol{eta} recruitment. Overall, these findings demonstrate that Lsm12 is a novel regulator mediating Pol{eta} deubiquitination to promote its recruitment under oxidative stress. Furthermore, this study provides a potential strategy to maintain the genome stability of industrial strains during fermentation.\n\nIMPORTANCEPol{eta} was shown to be critical for cell growth in the yeast Saccharomyces cerevisiae, and deletion of its corresponding gene RAD30 caused a severe growth defect under exposure to oxidative stress with 2 mM H2O2. Furthermore, we found that Lsm12 physically interacts with Pol{eta} and promotes Pol{eta} deubiquitination and recruitment. Overall, these findings indicate Lsm12 as a novel regulator mediating Pol{eta} deubiquitination that regulates its recruitment in response to DNA damage induced by oxidative stress.