DNMT1 depletion activates a pathway p14ARF/TP53 controlled that induces G1 arrest preventing DNA demethylation and aneuploidy

Background: Aneuploidy is considered the result of chromosome segregation errors caused by defects in the mitotic spindle assembly, centrosome duplication, cell-cycle checkpoints and epigenetic changes. Usually, aneuploidy affects negatively proliferation of normal cells. However, it is frequently associated with cancer that is characterized by a uncontrolled proliferation. Thus, understanding the pathway(s) that block proliferation of aneuploid cells might open new avenue to exploit new cancer therapies. O bservations: We found that in primary human fi broblasts (IMR90) knocking down of DNMT1, a member of epigenetic machinery is perceived by the cell as a stress signal that induces p14ARF …