The fact that Rrm1-Y285A acts as a dominant mutation contrasts with mutations that inactivate the exonuclease activity of Pol δ (Pold1e) and Pol ε (Polee), which are recessive mutants, and only Pold1e/e or Polee/e homozygous mice display mutator phenotypes and cancers (50,51). The gene discussed is RRM1; the disease is cancer.