Taming AID mutator activity in somatic hypermutation

Trends Biochem Sci. 2024 Apr 12:S0968-0004(24)00077-X. doi: 10.1016/j.tibs.2024.03.011. Online ahead of print.ABSTRACTActivation-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.PMID:38614818 | DOI:10.1016/j.tibs.2024.03.011
Source: Trends in Biochemical Sciences - Category: Biochemistry Authors: Source Type: research