CISPLATIN SENSITIVITY CORRELATES WITH ITS ABILITY TO CAUSE CELL-CYCLEARREST VIA A WEE1 KINASE-DEPENDENT PATHWAY IN SCHIZOSACCHAROMYCES-POMBE

Mutants of Schizosaccharomyces pombe were used to define genes involve d in the cell cycle arrest produced by cisplatin (DDP), an agent that causes both DNA damage and inhibition of DNA synthesis. Previous work has demonstrated that strains with defective or absent wee1(+) functio n fail to arrest in G(2) when DNA is damaged, but do arrest when DNA s ynthesis is inhibited (Rowley et al., 1992a, Nature, 356:353-355). Str ains defective in wee1(+) function, or in the ability of the wee1(+) k inase to regulate cdc2, failed to arrest following DDP exposure, as di d a rad1-1 mutant. All strains failing to arrest in G(2) were hypersen sitive to DDP. Thus, DNA damage rather than inhibition of DNA synthesi s is causative of DDP-induced cell cycle arrest. In addition, this wor k shows that the wee1(+) and rad1(+) gene products are required for su ccessful DDP-induced arrest, and suggests that the ability of S. pombe to arrest is a major determinant of sensitivity to DDP. (C) 1994 Wile y-Liss, Inc.