Polb, encoding DNA polymerase β, is a member of the DNA polymerase X family. It is mainly involved in eukaryotic DNA replication, DNA damage repair (especially base excision repair-BER), gene recombination, and cell cycle regulation [2]. In metazoans, it has been found to play a significant role in mitochondrial BER, safeguarding mitochondrial DNA (mtDNA) integrity and mitochondrial function, which is vital for organismal survival [1].

Mutations in Polb have been linked to various disease conditions. In mice, the POLB-Y265C mutation leads to the development of lupus-like disease. Mice with this mutation show high levels of antinuclear antibodies and severe glomerulonephritis [3]. Transplantation of bone marrow cells from POLB-Y265C/C mice into wild-type congenic mice demonstrated that the hematopoietic compartment from these mutant mice is sufficient for the development of autoimmune disease [4]. Also, a mouse model with decreased Pol β activity showed an autoimmune pathology resembling systemic lupus erythematosus (SLE), suggesting that decreased Pol β expression in humans may be an underlying cause of SLE [5]. In addition, in MMR-deficient acute lymphoblastic leukemia (ALL) cells, POLB plays a critical role in cell survival and thiopurine resistance. Depletion of POLB or treatment with its inhibitor oleanolic acid (OA) leads to synthetic lethality with MMR deficiency, increasing cellular AP sites, DNA strand breaks, and apoptosis [6].

In conclusion, Polb is essential for DNA repair processes, especially BER, and is crucial for maintaining genomic stability. Mouse models with Polb mutations have revealed its role in the development of autoimmune diseases like lupus and its significance in drug resistance mechanisms in ALL. These findings contribute to our understanding of the underlying mechanisms of these diseases and may potentially lead to new therapeutic strategies.