Nucleotide level mapping of uracils in murine heavy chain switch regions shows correlation between uracilation and positions of switch junctions created during class-switch recombination.

ABSTRACT: Introduction of uracils in specific regions within immunoglobulin genes by the activation-induced deaminase (AID) promotes mutations and double-strand breaks (DSBs). Although uracils are repaired through multiple DNA repair pathways, previous work has used mutations or DSBs as proxies for uracils and not mapped the uracils directly. We mapped uracils in the Ig heavy chain gene, Igh, in a murine cell line, CH12F3, undergoing class-switch recombination (CSR) using the uracil pull-down and sequencing technique. These cells undergo IgM-to-IgA switch upon expression of AID but do not undergo somatic hypermutation. We mapped uracils in cells defective in uracil repair and show that AID introduces high levels of uracils only in parts of switch-mu and switch-alpha regions and not in constan

SUBMITTER: Mohamad-Ramshan R 

PROVIDER: S-EPMC11897869 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature