Cell growth arrest by Rad2p induction in the absence of exogenous DNA damage causes delayed cell death in RAD9-dependent manner in yeast.

초록

Mitotic catastrophe provokes endopolylpoidy, giant cell formation, and eventually delayed cell death. RAD2 is a yeast homolog of XPG, which is an endonuclease involved in nucleotide excision repair. XPG defects cause xeroderma pigmentosum and Cockayne syndrome, that are characterized by drastically increased cancer disposition and premature aging, respectively. Here we show that Rad2p overexpression alone, in the absence of extrinsic DNA damage, causes cell growth arrest and mitotic catastrophe. Interestingly, the Rad2p-induced cell growth arrest is not caused by the catalytic activity of Rad2p, but rather by its C-terminal region. C-terminal region of Rad2p contains PCNA binding motif and Rad2p-PCNA interaction is mediated by the PCNA binding motif of Rad2p. This interaction could contribute to cell growth arrest by Rad2p overexpression. Cells growth-arrested by Rad2p induction do not show apoptotic phenotypes and deletion of YCA1, a yeast caspase homologue, does not affect cell growth arrest by Rad2p induction. However, Rad2p-induced cell growth arrest is released by rad9 deletion but is not affected by downstream DNA damage check point genes. These observations suggest that RAD2 has a function in coordinating cell cycle regulation and damaged DNA repair.