Alkbh2 protects against lethality and mutation in primary mouse embryonic fibroblasts

► Alkbh2 and Alkbh3 are Fe(II)/α-ketoglutarate-dependent dioxygenases both protect primary MEFs from cytotoxic alkylation damage. ► Only Alkbh2 protects primary cells from mutagenic alkylation damage. ► Alkbh2 and Alkbh3 have similar substrate specificity but provide different protection against alkylation damage. ► Alkbh2 and Alkbh3 protection against spontaneous and induced C→T and C→A mutations and methylmethane sulfonate induced A→T mutations.