Ung, short for uracil DNA glycosylase, is a key member of the base excision repair complex. It plays a crucial role in maintaining genomic stability by removing uracils from DNA, initiating high-fidelity base excision repair [2,4]. During B-cell development, it is involved in immunoglobulin (Ig) somatic hypermutation (SHM) and class switch recombination (CSR), processes that are essential for the adaptive immune response [1,2,3,6,7].

In mouse models, AID deficiency abolishes both CSR and SHM, while UNG-deficient mice have drastically reduced CSR but augmented SHM, suggesting differential functions of UNG in these processes [1]. The UNG-RPA interaction has been found to govern the choice between high-fidelity and mutagenic uracil repair. Mutants of UNG or RPA unable to interact only support high-fidelity repair, with transversions at the Ig variable region abated while CSR is still supported [2]. Also, UNG deficiency reduces B-cell clonal expansion in the germinal center in mice and blocks the proliferation of tumor B cells expressing AID, indicating its role in protecting B cells from AID-induced telomere loss [5].

In conclusion, Ung is essential for DNA repair, especially in maintaining genomic stability during B-cell development and antibody diversification. The study of Ung-deficient mouse models has provided valuable insights into its role in CSR, SHM, and protection against B-cell lymphoma, highlighting its significance in understanding the mechanisms of immune-related diseases and potentially guiding the development of novel therapeutic strategies [1,2,5].