Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation

Authors:
Open Access
Publisher website
Google Scholar
Abstract
Significance: Error-prone DNA repair of activation-induced cytidine deaminase (AID)-induced lesions in B cells is known to cause hypermutation of the antibody genes and, when coupled with selection mechanisms in germinal centers, leads to increased affinity of antibody. These lesions can also lead to substantial genomic instability that can promote lymphomagenesis, and the cause of error-prone repair is unknown. We have found that expression of an essential DNA repair protein, AP endonuclease (APE) 1, is dramatically reduced in mouse germinal center B cells where somatic hypermutation occurs. By contrast, the very inefficient homologue, APE2, becomes highly expressed. We show that APE2 promotes mutations and present a model proposing that differential expression of APE homologues in germinal centers is a major reason for error-prone repair of AID-induced lesions.

This publication has 57 references indexed in Scilit: