FAM72A antagonizes UNG2 to promote mutagenic repair during antibody maturation.

ABSTRACT: Activation-induced cytidine deaminase (AID) catalyses the deamination of deoxycytidines to deoxyuracils within immunoglobulin genes to induce somatic hypermutation and class-switch recombination^1,2. AID-generated deoxyuracils are recognized and processed by subverted base-excision and mismatch repair pathways that ensure a mutagenic outcome in B cells^3-6. However, why these DNA repair pathways do not accurately repair AID-induced lesions remains unknown. Here, using a genome-wide CRISPR screen, we show that FAM72A is a major determinant for the error-prone processing of deoxyuracils. Fam72a-deficient CH12F3-2 B cells and primary B cells from Fam72a^-/- mice exhibit reduced class-switch recombination and somatic hypermutation frequencies at immunoglobulin and

SUBMITTER: Feng Y 

PROVIDER: S-EPMC9425297 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature