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Cisplatin sensitivity correlates with its ability to cause cell cycle arrest via a wee1 kinase‐dependent pathway in schizosaccharomyces pombe
Author(s) -
Thiebaut Franz,
Enns Robert,
Howell Stephen B.
Publication year - 1994
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041590315
Subject(s) - schizosaccharomyces pombe , wee1 , cell cycle checkpoint , dna damage , cyclin dependent kinase 1 , biology , dna repair , mutant , cell cycle , chek1 , dna , cisplatin , microbiology and biotechnology , gene , genetics , chemotherapy
Mutants of Schizosaccharomyces pombe were used to define genes involved 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 wee 1 + function fail to arrest in G 2 when DNA is damaged, but do arrest when DNA synthesis is inhibited (Rowley et al., 1992a, Nature, 356 :353–355). Strains defective in wee 1 + function, or in the ability of the wee 1 + kinase to regulate cdc2, failed to arrest following DDP exposure, as did a rad1‐1 mutant. All strains failing to arrest in G 2 were hypersensitive to DDP. Thus, DNA damage rather than inhibition of DNA synthesis is causative of DDP‐induced cell cycle arrest. In addition, this work shows that the wee 1 + and rad 1 + gene products are required for successful DDP‐induced arrest, and suggests that the ability of S. pombe to arrest is a major determinant of sensitivity to DDP. © 1994 wiley‐Liss, Inc.