Mitotic catastrophe induced by overexpression of budding yeast Rad2p.
Mitotic catastrophe provokes endopolyploidy, giant cell formation and, eventually, delayed cell death. Mitotic catastrophe is induced by defective cell cycle checkpoints and by some anticancer drugs, ionizing radiation and microtubule-destabilizing agents. RAD2 is a yeast homologue of XPG, which is a human endonuclease involved in nucleotide excision repair. Here we show that Rad2p overexpression alone, in the absence of extrinsic DNA damage, 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. 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 checkpoint genes. These observations suggest that RAD2 has a function in coordinating cell cycle regulation and damaged DNA repair.
Kang
Mi-Sun
MS
Department of Pharmacology, Inha Research Institute for Medical Sciences, Incheon 400-712, Republic of Korea.
Yu
Sung-Lim
SL
Lim
Hyun-Sook
HS
Choi
Bohwa
B
Park
Chang-Shin
CS
Kang
Ju-Hee
JH
Lee
Sung-Keun
SK
D020169:Caspases / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D004706:Endodeoxyribonucleases / Q000096:biosynthesis* / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D008938:Mitosis; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000235:genetics
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; C073998:RAD2 protein, S cerevisiae; C069930:rad9 protein; D004706:Endodeoxyribonucleases; D020169:Caspases; C456272:MCA1 protein, S cerevisiae