Yanyan Wang, Senxin Zhang, Xinrui Yang, Joyce K Hwang, Chuanzong Zhan, Chaoyang Lian, Chong Wang, Tuantuan Gui, Binbin Wang, Xia Xie, Pengfei Dai, Lu Zhang, Ying Tian, Huizhi Zhang, Chong Han, Yanni Cai, Qian Hao, Xiaofei Ye, Xiaojing Liu, Jiaquan Liu, Zhiwei Cao, Shaohui Huang, Jie Song, Qiang Pan-Hammarström, Yaofeng Zhao, Frederick W Alt, Xiaoqi Zheng, Lin-Tai Da, Leng-Siew Yeap, Fei-Long Meng
Somatic hypermutation (SHM), initiated by activation-induced cytidine deaminase (AID), generates mutations in the antibody-coding sequence to allow affinity maturation. Why these mutations intrinsically focus on the three nonconsecutive complementarity-determining regions (CDRs) remains enigmatic. Here, we found that predisposition mutagenesis depends on the single-strand (ss) DNA substrate flexibility determined by the mesoscale sequence surrounding AID deaminase motifs. Mesoscale DNA sequences containing flexible pyrimidine-pyrimidine bases bind effectively to the positively charged surface patches of AID, resulting in preferential deamination activities...
May 11, 2023: Cell