The disclosure provides a method of inhibiting proliferation of a cell, inhibiting m3C formation in a cell, inhibiting activity of Mettl8 in a cell, or activating ATM and p53 in a cell, the method comprising contacting the cell with a Mettl8 inhibitor. The disclosure also provides a composition comprising a cell with a reduced expression or activity of Mettl8. In another aspect, the disclosure provides methods of rendering a tumor cell sensitive to a cancer therapy.