Subsequent in-depth analyses revealed that SKP1 silencing, a component of the SCF (SKP1, CUL1, FBox) E3 ubiquitin ligase complex, corresponded with increases in CIN phenotypes, replication stress, DNA double-strand breaks (DSBs), numerical changes in chromosome numbers and chromothriptic events that were rescued following co-silencing with Cyclin E1 (CCNE1), a substrate of the SCF complex. This evidence concerns the gene CUL1 and cervical squamous intraepithelial neoplasia.