Base Excision Repair in the Immune System: Small DNA Lesions With Big Consequences.
Level 5 - mechanism / opinion, no new human data
Narrative review and mechanism-based reasoning without original clinical trial data
PubMed 32547565 · doi:10.3389/fimmu.2020.01084
What was done
This narrative review synthesizes mechanistic, preclinical, and clinical literature on the base excision repair (BER) pathway in the immune system, specifically examining its contributions to genomic integrity, immunoglobulin class switch recombination, somatic hypermutation, B-cell malignancies, and autoimmune diseases.
What was found
Endogenous chemical base damage occurs at an estimated 10,000 to 30,000 lesions per cell per day. The review describes how BER processes activation-induced cytidine deaminase (AID)-generated uracil lesions into DNA double-strand breaks required for class switch recombination, and drives error-prone repair during somatic hypermutation at immunoglobulin loci. It highlights that breakdown of BER fidelity outside immunoglobulin loci is linked to mutations and chromosomal translocations in B-cell tumors, while BER defects in animal models cause autoimmunity through both B-cell intrinsic and extrinsic pathways. No original empirical data or effect sizes are reported in the abstract.
Why it matters
It clarifies how the BER pathway uniquely balances high-fidelity genome protection with programmed mutagenic diversification in adaptive immunity, highlighting how defects can lead to cancer or autoimmunity.
Limits
This is a narrative review without systematic search criteria or meta-analytic data synthesis. No primary human trial data, sample sizes, or quantitative risk estimates are provided.
Cited by
- context Human DNA incurs roughly 10,000 injuries per day, or about seven per minute.