In fact, many of the aberrant phenotypes we observed following SKP1 silencing and attributed to a lack of CCNE1 protein turnover, phenocopy those identified following genomic amplification or induced overexpression of CCNE1. Thus, we have established a novel, yet complementary mechanism whereby the lack of proteolytic degradation of CCNE1 stemming from a defective SCF complex induces replication stress, DSBs and CIN, which are enabling features of cancer. This evidence concerns the gene SKP1 and cancer.