Lsm12 mediates Pol·q deubiquitination to help Saccharomyces cerevisiae resist oxidative stress

Abstract

15In Saccharomyces cerevisiae, the Y-family DNA polymerase η (Polη) regulates genome stability 16 in response to different forms of environmental stress by translesion DNA synthesis. To elucidate 17 the role of Polη in oxidative stress-induced DNA damage, we deleted or overexpressed the 18 corresponding gene RAD30, and used transcriptome analysis to screen the potential genes 19 associated with RAD30 to respond to DNA damage. Under 2 mM H 2 O 2 , deletion of RAD30 20 resulted in a 2.2-fold decrease in survival and a 2.8-fold increase in DNA damage, whereas 21 overexpression of RAD30 increased survival and decreased DNA damage by 1.2-and 1.4-fold, 22 IMPORTANCE 34Polη was shown to be critical for cell growth in the yeast Saccharomyces cerevisiae, and deletion 35 of its corresponding gene RAD30 caused a severe growth defect under exposure to oxidative 36 stress with 2 mM H 2 O 2 . Furthermore, we found that Lsm12 physically interacts with Polη and 37 promotes Polη deubiquitination and recruitment. Overall, these findings indicate Lsm12 as a 38 novel regulator mediating Polη deubiquitination that regulates its recruitment in response to 39 DNA damage induced by oxidative stress. 40