A thermophilic 8-oxoguanine DNA glycosylase from Thermococcus barophiluss Ch5 is a new member of AGOG DNA glycosylase family  

作　　者：Lei Wang Donghao Jiang Likui Zhang 

机构地区：[1]College of Environmental Science and Engineering,Marine Science&Technology Institute,Yangzhou University,Yangzhou 225127,China [2]Guangling College,Yangzhou University,Yangzhou 225000,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第12期1801-1810,共10页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Natural Science Foundation of Jiangsu Province(,No.,BK20191219),High-Level Talent Support Program of Yangzhou University.

摘　　要：8-Oxoguanine(8oxoG)in DNA is a major oxidized base that poses a severe threat to genome stability.To counteract the mutagenic effect generated by 8oxoG in DNA,cells have evolved 8oxoG DNA glycosylase(OGG)that can excise this oxidized base from DNA.Currently,OGG enzymes have been divided into three families:OGG1,OGG2 and AGOG(archaeal 8oxoG DNA glycosylase).Due to the limited reports,our understanding on AGOG enzymes remains incomplete.Herein,we present evidence that an AGOG from the hyperthermophilic euryarchaeon Thermo Coccus barophilus Ch5(Tb-AGOG)excises 8oxoG from DNA at high temperature.The enzyme displays maximum efficiency at 75°C–95°C and at pH 9.0.As expected,Tb-AGOG is a bifunctional glycosylase that harbors glycosylase activity and AP(apurinic/apyrimidinic)lyase activity.Importantly,we reveal for the first time that residue D41 in Tb-AGOG is essential for 8oxoG excision and intermediate formation,but not essential for DNA binding or AP cleavage.Furthermore,residue E79 in Tb-AGOG is essential for 8oxoG excision and intermediate formation,and is partially involved in DNA binding and AP cleavage,which has not been described among the reported AGOG members to date.Overall,our work provides new insights into catalytic mechanism of AGOG enzymes.

关 键 词：hyperthermophilic Archaea 8-oxoguanine 8oxoG DNA glycosylase biochemical characteristic base excision repair 

分 类 号：O64[理学—物理化学]