Restoring SETDB2 in SETDB2 knockdown SUM159PT breast cancer cells (Fig. 1E) significantly decreased the percentage of abnormal nuclei in SUM159PT cells (Fig. S2A and Fig. 1F), rescued the abnormal phenotype of spindle and chromosome segregation in metaphase and anaphase (Fig. S2B and Fig. 1G), and decreased the percentage of G2/M arrested cell in SUM159PT breast cancer cells (Fig. S2C and Fig. 1H). Here, SETDB2 is linked to breast cancer.