To explain the tumorigenic mechanism associated with the genome hypomethylation induced by the disruption of the Dnmt1/PCNA/UHRF1 interactions, we demonstrate that the loss of these interactions is an event at the origin of the 1) chromosomal instability induced by the hypomethylation of DNA repeat element and 2) hypomethylation-mediated overexpression of specific genes such as the PDGF-B, survivin, H-ras, and MGMT genes i.e. genes coding for oncogenes or proteins participating to the acquisition of hallmarks of cancer [25], [26], [27], [28], [29]. This evidence concerns the gene DNMT1 and cancer.