Taming AID mutator activity in somatic hypermutation.
Trends Biochem Sci
; 49(7): 622-632, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38614818
ABSTRACT
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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citidina Desaminase
/
Hipermutação Somática de Imunoglobulina
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article