Lsm12 Mediates Deubiquitination of DNA Polymerase η To Help Resist Oxidative Stress.

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