c-MYC delays prometaphase by direct transactivation of MAD2 and BubR1: identification of mechanisms underlying c-MYC-induced DNA damage and chromosomal instability.

摘要: Here we show that the human BubR1 and MAD2 genes, which encode inhibitors of anaphase promoting complex (APC/C), are directly activated by oncogenic transcription factor c-MYC via E-box sequences in their first introns. Activation a conditional allele delayed progression through mitosis pro-metaphase MAD2- BubR1-dependent manner. A fraction daughter cells derived from extended mitotic events underwent synchronous apoptosis, was part mediated BubR1. Furthermore, activation resulted CIN (chromosomal instability) diploid MIN (microsatellite cell line DLD-1 further enhanced aneuploid CIN-line MCF7. Unexpectedly, c-MYC-induced independent BubR1/MAD2 expression delay. Therefore, may be caused alternative pathways. We observed induced DNA double-strand breaks, as evidenced formation γ-H2AX foci, colocalized with foci active D...