Taming AID mutator activity in somatic hypermutation.

Autor: Qin Y; Key Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences; Shanghai 200031, China., Meng FL; Key Laboratory of RNA Science and Engineering, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences; Shanghai 200031, China. Electronic address: feilong.meng@sibcb.ac.cn.
Jazyk: angličtina
Zdroj: Trends in biochemical sciences [Trends Biochem Sci] 2024 Jul; Vol. 49 (7), pp. 622-632. Date of Electronic Publication: 2024 Apr 12.
DOI: 10.1016/j.tibs.2024.03.011
Abstrakt: Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) by introducing base substitutions into antibody genes, a process enabling antibody affinity maturation in immune response. How a mutator is tamed to precisely and safely generate programmed DNA lesions in a physiological process remains unsettled, as its dysregulation drives lymphomagenesis. Recent research has revealed several hidden features of AID-initiated mutagenesis: preferential activity on flexible DNA substrates, restrained activity within chromatin loop domains, unique DNA repair factors to differentially decode AID-caused lesions, and diverse consequences of aberrant deamination. Here, we depict the multifaceted regulation of AID activity with a focus on emerging concepts/factors and discuss their implications for the design of base editors (BEs) that install somatic mutations to correct deleterious genomic variants.
Competing Interests: Declaration of interests The authors declare no conflicts of interest.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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