title: Mitotic catastrophe induced by overexpression of budding yeast Rad2p.
abstract: 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.
authors.affiliation: Department of Pharmacology, Inha Research Institute for Medical Sciences, Incheon 400-712, Republic of Korea.
authors.forename: Mi-Sun
authors.initials: MS
authors.lastname: Kang
authors.forename: Sung-Lim
authors.initials: SL
authors.lastname: Yu
authors.forename: Hyun-Sook
authors.initials: HS
authors.lastname: Lim
authors.forename: Bohwa
authors.initials: B
authors.lastname: Choi
authors.forename: Chang-Shin
authors.initials: CS
authors.lastname: Park
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Kang
authors.forename: Sung-Keun
authors.initials: SK
authors.lastname: Lee
mesh_terms: 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
chemical_list: 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