OGG1 Arginine Methylation Is Involved In The Study Of DNA Damage Mechanisms

DNA contains genetic information of organisms.The high fidelity of DNA replication ensures the stability of biological genetics.However,DNA suffers damage all the time.Reactive oxygen species?ROS?can cause oxidative stress and DNA damage due to the high oxidation properties.Since guanine?G?has a low redox potential,the main oxidation product of DNA molecules is 8-oxo-guanine?8-oxo G?.8-oxo G is a biomarker of DNA oxidative damage.It is highly mutagenic and produces G:C-T:A transversion mutations during DNA replication.In order to ensure the high stability of genetic information,cells developed a series of repair mechanisms during evolution.In mammals,this single-base lesion is mainly eliminated through the8-oxoguanine DNA glycosylase1?OGG1?-mediated base excision repair?BER?pathway.BER is an important repair system to maintain DNA stability,and is also responsible for repairing DNA damage to the nucleus and mitochondria.In recent years,more and more studies have shown that most proteins involved in DNA damage repair are regulated by post-translational modification?PTM?,including that arginine methylation regulating various BER proteins.In this research,we first discovered the arginine methylation of OGG1.Protein arginine methyltransferase1?PRMT1?catalyed the arginine methylation of OGG1both in vivo and in vitro.The enzyme activity assay showed arginine methylation inhibited the endonuclease activity of OGG1.In cells,the methylation of OGG1 is at the basal level under conventional culture.Under oxidative stress,such as H₂O₂treatment,there was an increased adhesion between OGG1 and PRMT1.And the arginine methylation level of OGG1 was significantly increased as well.In addition,the methylation-deficient OGG1 showed a significant reduction in nuclear localization.OGG1 methylation-deficient cells showed higher DNA damage under oxidative stress and also an increased release of mitochondrial cytochrome c.These evidences indicate that OGG1 can be methylated by arginine methyltransferase,which plays an important role in cell resistance to oxidative stress-induced DNA damage.In summary,this study shows the functions of the arginine methylation modification of OGG1 in regulating its endonuclease activity and subcellular organelle localization,which is an important supplement to the regulatory network of OGG1 post-translational modification.