The conclusions of this study imply that the high prevalence of mutations that occur in a large variety of cancers harboring somatic Polε proofreading domain mutations (22, 23, 24, 25, 26, 27, 28, 29) derive from PCNA ubiquitination and Polζ dependent extension of synthesis from Polδ generated mispairs on the leading strand that do not get removed in the absence of Polε proofreading function. The gene discussed is POLD1; the disease is cancer.