Human papillomaviruses (HPVs) which cause various epithelial cancers, produce two proteins, E6 and E7, whose expression allows bypass or overriding of normal DNA damage and spindle checkpoint signals, primarily through inactivation of p53 and retinoblastoma family members, respectively ( 11, 16, 17). Also, in E6/E7 cells with DNA damage, while Cdc20 is complexed with BubR1, indicating an active checkpoint, it is also present in complexes free of BubR1, presumably allowing APC/C activity and slippage through the checkpoint.įailure to activate cell cycle checkpoints in the presence of any DNA damage leads to genomic instability, polyploidy, and subsequently, aneuploidy, which is a hallmark of many cancers ( 26). Proteasomal degradation of cyclin B by anaphase-promoting complex/cyclosome (APC/C) is, in part, due to elevated levels of the E2-conjugating enzyme, Ubch10, and the substrate recognition protein, Cdc20, of APC/C. Also, as required for exit from mitosis, cyclin B is degraded in these cells, permitting initiation of the next round of DNA synthesis and cell cycle progression. Here, we show that in the presence of DNA damage, E6/E7 cells have elevated levels of cyclin B, which would allow entry into mitosis. Little is known about the mechanism that allows these cells to gain entry into and exit from mitosis. However, E6/E7-expressing cells (E6/E7 cells) have the ability to enter and exit mitosis in the presence of DNA damage and continue with the next round of the cell cycle. Normally, cells with DNA damage that override the G 2 damage checkpoint would precociously enter mitosis and ultimately face mitotic catastrophe and apoptotic cell death. Cells expressing human papillomavirus type 16 (HPV-16) E6 and E7 proteins exhibit deregulation of G 2/M genes, allowing bypass of DNA damage arrest signals.
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