Radiation-Induced Mitotic Delay: A Genetic Characterization in the Fission Yeast

Radiation-induced mitotic delay is under investigation in the fission yeast, Schizosaccharomyces pombe. A large range of cell cycle- and radiation-sensitive mutants of this yeast is available to facilitate this effort. Through an examination of such mutants it has been shown that the X-ray transition point and the p34 ^cdc2 execution point are coincident; <tex-math>$wee1^{-}$</tex-math> strains are not delayed by irradiation; and the radiation-sensitive mutants rad1-1, rad3-136, rad9-192, and rad17-W are not delayed by radiation or by inhibitors of DNA synthesis, including hydroxyurea. A model is proposed: Damaged DNA generates a signal to delay mitosis which is carried by the products of the rad genes to activate the tyrosine kinase <tex-math>${\rm p}110^{{\rm wee}1}$</tex-math>. This in turn inactivates the serine/threonine kinase p34 ^cdc2, thereby blocking entry to mitosis. Unreplicated DNA also initiates a signal to delay mitosis which is carried by these same rad genes but, as indicated in the literature, transmission to p34 ^cdc2 does not require <tex-math>${\rm p}110^{{\rm wee}1}$</tex-math>. The delay-deficient rad mutants may possess some properties of tumor suppressor genes, with implications for mutagenesis and oncogenesis.