Reduction of the SAC protein Mad2 (mitotic arrest deficient 2) or its partner proteins (e.g. BubR1: Budding uninhibited by benzimidazoles Related 1) have been shown to shorten metaphase, causing CIN, aneuploidy and tumour susceptibility in humans and mouse models [15]–[17]. This evidence concerns the gene BUB1B and cervical squamous intraepithelial neoplasia.