主講人：張宇航博士，耶魯大學

主講人簡介🚣🏿🖕🏻：張宇航博士，現任耶魯大學醫EON4博士後，2004年本科畢業於吉林大學，2007年於吉林大學獲得博士學位，2011年於中科院生化與細胞研究所獲得博士學位。在Nature, Cell等雜誌發表研究論文

報告時間：6月13日（周四）15:30-16:30

報告地點：閔行校區EON体育4平台2號樓116會議室

聯系人🫱🏻：楊廣宇

報告簡介：

Domestication of a transposon (a DNA sequence that can change its position in a genome) to give rise to the RAG1–RAG2 recombinase (RAG) and V(D)J recombination, which produces the diverse repertoire of antibodies and T cell receptors, was a pivotal event in the evolution of the adaptive immune system of jawed vertebrates. The evolutionary adaptations that transformed the ancestral RAG transposase into a RAG recombinase with appropriately regulated DNA cleavage and transposition activities are not understood. Here, beginning with cryo-electron microscopy structures of the amphioxus ProtoRAG transposase (an evolutionary relative of RAG), we identify amino acid residues and domains the acquisition or loss of which underpins the propensity of RAG for coupled cleavage, its preference for asymmetric DNA substrates and its inability to perform transposition in cells. In particular, we identify two adaptations specific to jawed-vertebrates—arginine 848 in RAG1 and an acidic region in RAG2—that together suppress RAG-mediated transposition more than 1,000-fold. Our findings reveal a two-tiered mechanism for the suppression of RAG-mediated transposition, illuminate the evolution of V(D)J recombination and provide insight into the principles that govern the molecular domestication of transposons.