Proliferation recovery of Rad2p-induced mitotic catastrophe in Saccharomyces cerevisiae is related to increased genomic instability.

초록

Yeast RAD2, a counterpart of human XPG, is an essential gene for nucleotide excision repair. Rad2p is an endonuclease that incises the 3' side of a DNA damaged lesion. However, over-expression of Rad2p provokes cell growth arrest, resulting in mitotic catastrophe as evidenced by formation of enlarged cells and micro-nucleation. Interestingly, the effect of Rad2p on cell growth arrest is not caused by its endonuclease activity, and it has been suggested that Rad2p might be involved in cell cycle regulation. Mitotic catastrophe mainly resulted in cell death but also functions as a survival mechanism. Using RAD2, we show that some yeast cells growth-arrested by Rad2p-induced mitotic catastrophe regain their ability to proliferate mainly because some Rad2p-induced polyploid cells produce haploid cells with normal cell cycles. Rad2p overexpression also causes increased mutagenesis and the cells with recovered proliferative ability exhibit increased genomic instability, which in turn decreases Rad2p expression. From these results it is inferred that Rad2p-induced polyploid cells undergo increased genetic rearrangement resulting in production of haploid cells.