Opinion article in Trends in Immunology discusses the new concept of DNA mechanics code

Researchers from the laboratory of Leng-Siew Yeap at the Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine and Fei-Long Meng at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences have published an opinion article entitled "DNA flexibility can shape the preferential" online in Trends in Immunology. The article systematically reviews the history of antibody somatic hypermutation (SHM) and introduces the ancient and classic puzzle: "Why are complementarity-determining regions (CDRs) more susceptible to mutations than other regions?". Based on their recent landmark discoveries published in Cell, they provide an interesting and provocative discussion of DNA flexibility as a mediator of genetic function and aspects of the evolution of AID targeting via DNA flexibility. Finally, they also suggest the potential implications of the emerging concept of a DNA mechanical code for other cellular life processes, such as AID off-target mutations in cancer genomes and DNA damage repair processes.

During antibody affinity maturation, beneficial mutations occur preferentially in the DNA regions that encode antigen-contacting amino acids. The non-randomness of predisposed mutations has long been a mystery in immunology. They posit that ssDNA flexibility can be “sensed” by AID binding, fine-tunes deamination activity, and manifests as regional hypermutation, which could be an exemplar of how general DNA mechanics affect a cellular process. This newly identified feature might answer a longstanding question in immunology, which is why the CDR coding sequences are preferentially mutated to generate beneficial mutations in fighting pathogens. In this model, the coding sequence plays a non-coding role through DNA mechanics, and this mechanics code of DNA could be a hidden piece of genetic information. In a general aspect, they think that many other physiological processes are also controlled by DNA mechanics and that the example of AID deamination is not an isolated case. These processes await identification and merit further investigation.

The first author is Yanyan Wang, a Yuhe Postdoctoral Fellow and a Shanghai Super Postdoctoral Fellow in Yeap lab. This work was supported by the Shanghai Jiao Tong University 2030 Initiative, National Natural Science Foundation of China, China Postdoctoral Science Foundation, and etc.

The Yeap lab welcomes enthusiastic students and postdoctoral fellows to join the group. Interested individuals can contact Dr Yeap at yeaplengsiew@shsmu.edu.cn.

SII website: https://www.shsmu.edu.cn/sii/info/1164/2452.htm

Article link: https://authors.elsevier.com/a/1iepr_XTJFb%7EW5