Caffeine can override the S-M checkpoint in fission yeast.

Wang, S; Norbury, C; Harris, A; Toda, T

Journal article

Caffeine can override the S-M checkpoint in fission yeast.

Abstract:: The replication checkpoint (or 'S-M checkpoint') control prevents progression into mitosis when DNA replication is incomplete. Caffeine has been known for some time to have the capacity to override the S-M checkpoint in animal cells. We show here that caffeine also disrupts the S-M checkpoint in the fission yeast Schizosaccharomyces pombe. By contrast, no comparable effects of caffeine on the S. pombe DNA damage checkpoint were seen. S. pombe cells arrested in early S phase and then exposed to caffeine lost viability rapidly as they attempted to enter mitosis, which was accompanied by tyrosine dephosphorylation of Cdc2. Despite this, the caffeine-induced loss of viability was not blocked in a temperature-sensitive cdc2 mutant incubated at the restrictive temperature, although catastrophic mitosis was prevented under these conditions. This suggests that, in addition to S-M checkpoint control, a caffeine-sensitive function may be important for maintenance of cell viability during S phase arrest. The lethality of a combination of caffeine with the DNA replication inhibitor hydroxyurea was suppressed by overexpression of Cds1 or Chk1, protein kinases previously implicated in S-M checkpoint control and recovery from S phase arrest. In addition, the same combination of drugs was specifically tolerated in cells overexpressing either of two novel S. pombe genes isolated in a cDNA library screen. These findings should allow further molecular investigation of the regulation of S phase arrest, and may provide a useful system with which to identify novel drugs that specifically abrogate the checkpoint control.

Publication status:: Published

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APA Style

Wang, S., Norbury, C., Harris, A., & Toda, T. (1999). Caffeine can override the S-M checkpoint in fission yeast. Journal of Cell Science, 112 ( Pt 6)(6), 927–937.

MLA Style

Wang, S., et al. “Caffeine Can Override the S-M Checkpoint in Fission Yeast.” Journal of Cell Science, vol. 112 ( Pt 6), no. 6, 1999, pp. 927–37.

Chicago Style

Wang, S, C Norbury, A Harris, and T Toda. 1999. “Caffeine Can Override the S-M Checkpoint in Fission Yeast.” Journal of Cell Science 112 ( Pt 6) (6): 927–37.
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