C-terminal region of Rad2p is important for cell growth arrest, implications for its involvement in cell cycle regulation by interaction with PCNA

초록

Mitotic catastrophe provokes endopolyploidy, giant cell formation and , eventually, delayed cell death. RAD2 is a yeast homolog of XPG, which is a human endonuclease invloved in nucleotide excision repair. Herem we show that Rad2p overexpression alone, in the absence of extrinsic DNA dmage, causes cell growth arrest and mitotic catastrophe. Interestingly, 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 overexpresson. Cells growth-arrested by Rad2p induction do not show apoptotic phwnotypes and deletion of YCA1, a yeast caspase homologue, does not affect cell growth arrest byRad2p induction. However, Rad2p-induced cell growth arrest is released by rad9 deletion but is not affected by downstream DNA damage checkpoint genes. These observations suggest that RAD2 has a function in coordinating cell cycle regulation and damaged DNA repair.