ArticleProceedings of the National Academy of Sciences of the United States of America2014
Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Repertoire Sequencing of B Cells Elucidates the Role of UNG and Mismatch Repair Proteins in Somatic Hypermutation in Humans.Frontiers in immunology · 2019Pooled it
- Redundant mispair excision mechanisms in eukaryotic DNA mismatch repair.Nucleus (Austin, Tex.) · 2026Review
- Contrasting roles of APE1 and APE2 in genome maintenance, cancer development, and therapeutic targeting.NAR cancer · 2025Review
- Molecular mechanisms of DNA lesion and repair during antibody somatic hypermutation.Science China. Life sciences · 2024Review
- Mechanism and regulation of secondary immunoglobulin diversification.Cell cycle (Georgetown, Tex.) · 2023Review
- APE2 Promotes AID-Dependent Somatic Hypermutation in Primary B Cell Cultures That Is Suppressed by APE1.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Recent advances in therapeutic CRISPR-Cas9 genome editing: mechanisms and applications.Molecular biomedicine · 2023Review
- DNA repair mechanisms that promote insertion-deletion events during immunoglobulin gene diversification.Science immunology · 2023Article
- A Novel HypomorphicAntioxidants & redox signaling · 2023Article
- HMCES protects immunoglobulin genes specifically from deletions during somatic hypermutation.Genes & development · 2022Article
- APE1/Ref-1 Role in Inflammation and Immune Response.Frontiers in immunology · 2022Review
- Nucleotide Pool Imbalance and Antibody Gene Diversification.Vaccines · 2021Review
- Cisplatin-Mediated Upregulation of APE2 Binding to MYH9 Provokes Mitochondrial Fragmentation and Acute Kidney Injury.Cancer research · 2021Article
- Intrinsic Strand-Incision Activity of Human UNG: Implications for Nick Generation in Immunoglobulin Gene Diversification.Frontiers in immunology · 2021Article
- Tracking Immunoglobulin Repertoire and Transcriptomic Changes in Germinal Center B Cells by Single-Cell Analysis.Frontiers in immunology · 2021Article
- Impact ofMicroorganisms · 2020Article
- DNA Repair Biomarker for Lung Cancer Risk and its Correlation With Airway Cells Gene Expression.JNCI cancer spectrum · 2020Article
- Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences.Frontiers in immunology · 2020Review
- AID Phosphorylation Regulates Mismatch Repair-Dependent Class Switch Recombination and Affinity Maturation.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Article
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9 authors.
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Abstract
Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase β. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells.
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