Fam72a, a poorly characterized yet evolutionarily conserved gene across multicellular organisms, has emerged as a significant player in multiple biological processes. It is involved in cell-cycle regulation, interacting with key components of the cell-cycle machinery and apoptosis-related pathways. It also plays a crucial role in antibody maturation and mutagenic DNA repair pathways [2].

In Fam72a-deficient CH12F3-2 B cells and primary B cells from Fam72a-/-mice, reduced class-switch recombination and somatic hypermutation frequencies at immunoglobulin and Bcl6 genes were observed, along with reduced genome-wide deoxyuracils [1]. The somatic hypermutation spectrum in these cells was opposite to that in UNG2-deficient mice, suggesting hyperactivity of UNG2 in FAM72A-deficient cells. FAM72A binds to UNG2, reducing UNG2 protein levels in the G1 phase, leading to error-prone DNA repair [1]. In addition, Fam72a-/-B cells show defective class-switch recombination due to UNG2 upregulation, and reduced somatic hypermutation [3].

In conclusion, Fam72a is essential for error-prone DNA repair during antibody maturation by regulating UNG2 levels. The use of Fam72a-/-mouse models has revealed its significance in antibody-related biological processes. Moreover, its overexpression in many cancers may promote mutagenesis, indicating its potential importance in cancer research [1,3].