Translesion synthesis of apurinic/apyrimidic site analogues by Y-family DNA polymerase Dbh from Sulfolobus acidocaldarius  

作　　者：Weiwei Wang Huan Zhou Li Peng Feng Yu Qin Xu Qisheng Wang Jianhua He Xipeng Liu 

机构地区：[1]Shanghai Institute of Applied Physics,Chinese Academy of Sciences,Shanghai 201800,China [2]University of Chinese Academy of Sciences,Beijing 100049,China [3]State Key Laboratory of Microbial Metabolism,School of Life Sciences and Biotechnology,Shanghai Jiao Tong University,Shanghai 200240,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第5期637-646,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 National Key R&D Program of China(Nos.2018YFC0310704 and 2018YFC0309806);the National Natural Science Foundation of China(No.U1832161);the China Ocean Mineral Resources R&D Association(No.DY135-B2-12).

摘　　要：Apurinic/apyrimidic(AP)sites are severe DNA damages and strongly block DNA extension by major DNA polymerases.Y-family DNA polymerases possess a strong ability to bypass AP sites and continue the DNA synthesis reaction,which is called translesion synthesis(TLS)activity.To investigate the effect of the molecular structure of the AP site on the TLS efficiency of Dbh,a Y-family DNA polymerase from Sulfolobus acidocaldarius,a series of different AP site analogues(various spacers)are used to characterize the bypass efficiency.We find that not only the molecular structure and atomic composition but also the number and position of AP site analogues determine the TLS efficiency of Dbh.Increasing the spacer length decreases TLS activity.The TLS efficiency also decreases when more than one spacer exists on the DNA template.The position of the AP site analogues is also an important factor for TLS.When the spacer is opposite to the first incorporated dNTPs,the TLS efficiency is the lowest,suggesting that AP sites are largely harmful for the formation of hydrogen bonds.These results deepen our understanding of the TLS activity of Y-family DNA polymerases and provide a biochemical basis for elucidating the TLS mechanism in Sulfolobus acidocaldarius cells.

关 键 词：translesion synthesis Sulfolobus acidocaldarius Y-family DNA polymerase DBH AP site analogues 

分 类 号：O62[理学—有机化学]