Effects of a novel DNA-damaging agent on the budding yeastSaccharomyces cerevisiae cell cycle

✍ Scribed by Popolo, Laura; Viganò, Ferdinando; Erba, Eugenio; Mongelli, Nicola; D'incalci, Maurizio

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: English
• Weight: 756 KB
• Volume: 12
• Category: Article
• ISSN: 0749-503X
• DOI: 10.1002/(sici)1097-0061(19960330)12:4<349::aid-yea917>3.0.co;2-o

✦ Synopsis

We have investigated the effects on Succliaronijxes cerevisirie of a novel antitumour agent (FCE245 17 or Tallimustine) which causes selective alkylations to adenines in the minor groove of DNA. Tallimustine, added to wild-type cells for short periods, reduced the growth rate and increased the percentage of budded cells and delayed the cell cycle in the late S+G,+M phases. In the rad9A null mutant cells, Tallimustine treatment did not affect growth rate and the percentage of budded cells but greatly reduced cell viability compared to isogenic cells. Consistent with a role of RAD9 in inducing a transient delay in G, phase which preserves cell viability, the potent cytotoxic effect of the drug on rad9A cells was alleviated by treatment with nocodazole. Tallimustine was also found to delay the resumption from G, arrest of wild-type but not of rad9A cells. These data indicate that the effects of Tallimustine on cell cycle progression in yeast are mediated by the RAD9 gene product. From our data it appears that yeast could be a valuable model system to study the mode of action of this alkylating drug and of minor groove alkylators in general.