Yeast cDNA library screening for isolation of genes that modulate Rad2p-induced mitotic catastrophe

초록

DNA damage can cause mitotic catastrophe, which is characterized by suppressed mitotic cycling, delayed cell death and the formation of large polyploidy cells. Mitotic catastrophe is generally considered to be a type of cell death that is caused by extensive DNA damage during mitosis. Similar to the effects in mammalian cells, DNA damage causes cell cycle arrest at the G2/M phase in yeast, and cells with mitotic catastrophe undergo cell death. On the other hand, some mammalian cells whose cell cycle is arrested by mitotic catastrophe produce viable descendants that are able to undergo normal mitosis and genome reduction. Cells that resume mitosis after mitotic catastrophe have altered DNA integrity and demonstrate increased drug resistance. These results demonstrate that mitotic catastrophe after DNA damage serves as a cell survival in a harsh environment. However, the mechanism by which mitotic catastrophe induces polyploidy cells to undergo genome reduction to survive in a harsh environment is not clearly understood. Previously, we reported that over-expression of a DNA repair protein, Rad2p, evokes mitotic catastrophe and some cells growth-arrested by Rad2p-induced mitotic catastrophe regain their ability to proliferate. In order to understand the molecular basis of the regained proliferation ability, we isolated some genes that compromise Rad2p-induced mitotic catastrophe by screening yeast cDNA library. As the results, 51 genes were identified. We discussed the possible role of those genes in the reduction of Rad2p-induced mitotic catastrophe.