Min Emma Huang, Yining Qin, Yafang Shang, Qian Hao, Chuanzong Zhan, Chaoyang Lian, Simin Luo, Liu Daisy Liu, Senxin Zhang, Yu Zhang, Yang Wo, Niu Li, Shuheng Wu, Tuantuan Gui, Binbin Wang, Yifeng Luo, Yanni Cai, Xiaojing Liu, Ziye Xu, Pengfei Dai, Simiao Li, Liang Zhang, Junchao Dong, Jian Wang, Xiaoqi Zheng, Yingjie Xu, Yihua Sun, Wei Wu, Leng-Siew Yeap, Fei-Long Meng
Base editors (BEs) introduce base substitutions without double-strand DNA cleavage. Besides precise substitutions, BEs generate low-frequency 'stochastic' byproducts through unclear mechanisms. Here, we performed in-depth outcome profiling and genetic dissection, revealing that C-to-G BEs (CGBEs) generate substantial amounts of intermediate double-strand breaks (DSBs), which are at the centre of several byproducts. Imperfect DSB end-joining leads to small deletions via end-resection, templated insertions or aberrant transversions during end fill-in...
January 23, 2024: Nature Cell Biology